FSH Watch
Vol. 2 No. 2, Fall 1995
A publication of the FacioScapuloHumeral Society
Provided by the
FSH Society, Inc.
Inside ...
FSH Society Announces Completion of Patient Brochure for FSHD!
The FSH Society is pleased to announce publication of the pamphlet,
Facioscapulohumeral Dystrophy (FSHD). Since its inception, FSH
Society's goal has been to publish a comprehensive educational and
informational brochure on FSHD. Stephen J. Jacobsen, Ph.D., has written this
FSHD pamphlet for patients, the public, physicians, clinics and other health
professionals.
He is indebted to the editorial ideas of other members of the Scientific
Advisory Board of the FSH Society who are knowledgeable about FSHD in their
respective disciplines, including William Lewis III, M.D., University of
California, Davis, Paul Schultz, M.D., Children's Hospital in San
Diego, California, and Barbara Weiffenbach, Ph.D., of Genome Therapeutics,
Inc., Waltham, Massachusetts.
The FSHD brochure is designed for all readers, professional and
non-professional. A concerted effort was made to make it brief and easily read
without abridging information that readers will find useful.
Facioscapulohumeral dystrophy is a debilitating disease. It has significant
medical and health impacts on individuals, families and society. We hope this
brochure increases your understanding of this disease and that better
understanding of FSHD will help those who are living with and concerned about
this disease. Published as a pamphlet for wider distribution, the purpose of
this brochure is to increase public and medical awareness of FSHD and encourage
research toward understanding the cause and treatment of FSHD. We welcome your
comments and questions about the information presented. Following is the text
of this brochure.
v v v
Introduction
Facioscapulohumeral muscular dystrophy, sometimes abbreviated FSH or FSHD, is a
form of muscular dystrophy. The earliest clear report of FSHD as a distinct
type of muscular dystrophy was in 1886 by the two French physicians, Landouzy
and DŽjŽrine. Consequently, Landouzy-DŽjŽrine disease was a
name previously used to describe FSHD.
A DNA mutation causes FSHD, and most people who have the disease inherited that
mutation from a parent with FSHD. Progressive weakening and loss of skeletal
muscle are its major effects, but those affected by FSHD need additional
information. Further details about its nature and some basic understanding
about inheritance of genetic diseases are important to better understand FSHD.
The FSH Society hopes that the few minutes you spend reading this pamphlet will
better acquaint you with this unusual disease.
What Causes FSHD?
By going from the large (muscle) to the small (DNA), we can partially
understand the cause and origin of FSHD. DNA, short for deoxyribonucleic acid,
is a long molecule that is the genetic instructions for our characteristics and
traits. Discrete segments of DNA, genes, decide specific characteristics and
traits. Taken together, the combination of an estimated 100,000 genes makes
each of us "an original."
A mutation causes FSHD. A mutation is a sudden structural change in DNA. The
FSHD mutation and the affected gene are unknown. For most FSHD cases,
scientists have narrowed the location of the problem to a small, specific
section of DNA. Within that region, there are deletions of DNA associated with
most cases of FSHD.
What is the FSHD Syndrome?
The FSHD syndrome is the group of signs and manifestations, i.e., symptoms,
which collectively characterize the disease. Progressive weakening and loss of
skeletal muscle are the major symptoms of FSHD. The pattern of these weaknesses
is unusual. Facioscapulohumeral describes parts of the body where symptoms of
the disease are usually first seen: face (facio), shoulders (scapulo) and upper
arms (humeral). Early facial muscle weaknesses around the eyes and mouth, in
combination with specific shoulder muscle weaknesses, often support the
physician's conclusion that FSHD is the problem. A person may sleep
with their eyes partially open or may be unable to squeeze their eyes tightly
shut. A smile may be weak or asymmetrical, and things like puckering the lips
to blow up a balloon or whistle may be difficult. Typically, it will be
difficult to lift one or both arms over the head, and the weakened shoulder
muscles cannot hold the scapula flat against the back. Other subtle signs are
rounded shoulders and thin upper arms. Although the name suggest involvement of
muscles in only three body areas, other muscles usually weaken, including those
of the neck, torso and lower limbs. Early FSHD weaknesses do occur in the lower
legs and ankles, and occasionally the muscles of the forearms and hands
weaken.
There are other less common symptoms, such as some cases of a high frequency
hearing loss. Abnormalities of blood vessels in the back of the eye are
sometimes present, but they rarely lead to visual problems. It is not known how
often these symptoms occur in the general population of people with FSHD.
How is FSHD Inherited?
Most people who have FSHD inherited that mutation from a parent with FSHD.
Inheritance is the means of transmission of DNA, and therefore characteristics
and traits, from parent to child. Chromosomes are the vehicles for those
transmissions. Each chromosome contains a long, threadlike strand of DNA.
Humans have 23 pair of chromosomes in their cells. Children inherit one member
of each equivalent pair of chromosomes from each parent. Most FSHD cases occur
due to a DNA mutation on one member of the chromosome 4 pair. There are also
some occasional instances where symptoms are compatible with the FSHD syndrome,
but where genetic studies exclude chromosome 4 as the location of the FSHD
mutation. The chromosomal locations of these mutations are unknown.
Chromosome 4 is an autosome. An autosome is any chromosome other than a sex
chromosome (X or Y). When a person inherits a chromosome 4 with the FSHD
mutation, symptoms of FSHD develop. Since these symptoms occur in the presence
of the normal member of the chromosome 4 pair, the disease is considered
dominant. In genetics, FSHD is therefore an autosomal dominant inherited
disease. Since each parent donates only one member of each chromosome pair to a
child, the probability of passing the disease to an offspring is 50 percent.
(See Figure on page 21)
Inheritance of the FSHD Gene
How Many People Have This Disease
It is difficult to calculate the exact incidence of FSHD. It may be under
reported, but an accepted estimate of its occurrence in the general population
is one in 20,000. FSHD is not restricted to any particular racial group. It
occurs equally often in both sexes.
When Do Symptoms Appear?
Although the FSHD gene is present at birth, people with FSHD typically begin to
notice muscle weaknesses during teenage years. A physician can usually
recognize and diagnose FSHD by the age of 20. However, it is important to
realize that the beginning of symptoms is variable. Occasionally, a child, or
even an infant, has symptoms. Sometimes, muscle weaknesses are slight in the
60s and 70s.
What is Infantile FSHD?
There is an infantile form of FSHD. Infantile FSHD, or IFSHD, is rare and
accounts for perhaps five percent of FSHD cases. There are early facial
weaknesses during the first two years of life. Typical FSHD muscle weaknesses
also occur in the shoulders, upper arms, and lower legs and feet. As in other
FSHD cases, the rate or progress of these weaknesses is variable and hearing
losses and retinal abnormalities occur in some of these children.
The isolation and characterization of the FSHD gene will more fully clarify the
relationship between IFSHD and FSHD. It may also add insight to the possible
related question of why there is such wide variation in the expression of
FSHD.
What is the Prognosis of FSHD?
Predicting the probable course and outcome of the disease, i.e., the prognosis,
has its clinical certainties and uncertainties. There is certainty that some
skeletal muscles will weaken and waste throughout life, and that this can and
often does cause limitations on personal and occupational activities. FSHD does
not diminish the intellect. The heart and internal (smooth) muscles seem
spared, and except in rare cases, those with FSHD have a normal life span.
There are uncertainties. The rapidity and extent of muscle loss differ
considerably among FSHD patients, even among members of the same family. Some
report few difficulties throughout life, while in other cases an individual may
need a wheelchair because walking becomes too difficult or impossible. The
degree of severity in an FSHD parent cannot accurately predict the extent of
disabling effect that may develop in that parent's child.
Anyone acquainted with FSHD and those who have it, know that they are a group
of well adjusted, educated and motivated people who adjust to a legion of
adaptations. Muscle and motion are an important part of the full expression of
much of life. Often, there are losses difficult to define in clinical terms:
running, playing catch, walking in the sand on the beach, carrying a baby in
one's arms, and dancing with a loved one, to name a few. These losses
often eclipse the clinical certainties and are an unspoken and significant part
of the FSHD prognosis.
If a Family Member has FSHD, Could
I Have the FSHD Mutation?
If one has a blood parent, full sibling or other blood relative who has the
FSHD mutation, then one may be at risk to carry the FSHD mutation. There are
cases of FSHD that are quite mild during years where there are important
vocational, marital and family planning choices. It is sometimes helpful for
one who is at risk for FSHD to know if they carry the FSHD mutation.
Professionals with knowledge of genetics and inheritance can advise whether the
risk of FSHD exists. The FSH Society can provide answers and referrals about
questions of risk.
If a risk of having the FSHD gene exists, a physician can provide a medical
diagnosis to detect symptoms. Even an adult at risk, with no obvious symptoms,
should avail themselves of a diagnosis if they wish reassurance that the FSHD
gene is not likely present. The diagnosis consists of an assessment of any
personal and family history of FSHD, a physical examination and a review of
laboratory findings. These laboratory findings often include information from a
blood analysis, an electromyograph (EMG) and occasionally a muscle biopsy. An
EMG records abnormal electrical activity of a functioning skeletal muscle. A
biopsy consists of a small piece of muscle, analyzed for visible abnormalities
in the muscle tissue.
Are Treatments and
Aids Available for FSHD?
There is no treatment or cure for FSHD, but there are things that can alleviate
its effects. Since muscles do their work through stimulation by nerves,
neurologists are concerned with muscle and are often the primary physicians of
muscle disease clinics. Physiatrists are physicians who work with chronic
neuromuscular conditions. Periodic visits with a neurologist or physiatrist are
useful to monitor the progress of FSHD and to obtain referrals to other
professionals and services. An orthopedist, one concerned with the skeletal
system and associated muscles, joints and ligaments, can advise about lessening
walking problems and other functional problems of the muscular/skeletal
system.
Physical therapy, including light exercise, helps preserve flexibility.
Swimming is especially helpful in this regard by often making many movements
easier. One should stay as active as possible, with rest breaks as needed
during exercise and activities. Occupational therapy can help with suggestions
for adaptations and physical aids that can often partially "free"
a FSHD patient from some constrictions of the disease. Dieticians can help.
Maintain a good diet to avoid unnecessary weight and reduce stress on already
weakened muscles.
Some people with FSHD have had their scapula attached to the back to improve
motion of the arms. Immobilization of limbs for long periods poses a risk of
hastening muscle weakness. An individual who is considering such surgery should
consult with their neurologist or physiatrist and an orthopedic surgeon.
Discussion of this procedure with individuals who have undergone the surgery is
important. The FSH Society provides referrals to physicians and other
professionals.
FacioScapuloHumeral Society
3 Westwood Road
Lexington, MA 02420
617/860-0501
1507 Traske Road
Encinitas, CA 92024
619/632-8603
The FSH Society is a nonprofit, tax-exempt U.S. corporation. Established in
1991 by Daniel P. Perez, the Society addresses specific issues and needs
regarding facioscapulohumeral muscular dystrophy (FSHD). It actively promotes
research toward the prevention, cause and treatment of FSHD. It also helps FSHD
groups where individuals with like concerns have an opportunity to interact and
receive helpful information concerning day to day life with FSHD. The Society
further offers assistance to physicians and other professionals interested in
FSHD. Anyone with questions about FSHD should contact his or her physicians,
the FSH Society or their local Muscular Dystrophy Association.
Overview of Recent Mapping Studies of the FSHD Gene
by Evelyn Devine Gage, Ph.D
The initial mapping of the FSHD gene in 1990 to the long arm of chromosome 4
has led to an explosion of information and interest on the further subregional
localization and characterization of the gene. As the gene location of the FSHD
gene has been refined, more sophisticated questions have been asked about the
nature of the defect and the prevalence of the rate of new mutations.
Early mapping studies utilized a systematic and laborious technique known as
linkage analysis. This method is the proverbial "search for a needle in
the haystack." Researchers, drawing from a data base of RFLPs
(Restriction Fragment Length Polymorphisms) were able to establish linkage of
the FSHD gene to an area on the long arm of chromosome 4 (known as 4q35).
RFLP's are identified by using restriction enzymes. These are enzymes
which recognize very specific DNA sequences and which also cut (restrict) the
DNA whenever these sequences occur. When human DNA is cut by a restriction
enzyme, pieces (fragments) of different lengths will result and these pieces of
DNA can be separated by size. For example, the restriction enzyme known as
EcoRI recognizes the DNA sequence GAATTC, and every time the enzyme sees this
sequence it will cut the DNA. Among individuals there is a great deal of
variation in their DNA due to a low frequency of mutation, and when the DNA
from different individuals is cut by a restriction enzyme, fragments of
differing size are seen. The DNA from one individual as compared to the DNA
from another can be fingerprinted using this technique. This procedure can also
be used to map genes to specific human chromosomes and, in particular, to
isolate disease genes. When DNA is cut by a restriction enzyme, the fragments
can be separated by size in an agarose gel which acts as a sieve. If human DNA
is cut by the enzyme EcoRI and separated on a gel, it can be searched (or
probed) by a sensitive technique utilizing specific pieces of DNA derived from
known locations on the long arm of chromosome 4. Typically, these chromosome 4
pieces of DNA will be labeled radioactively and the resultant hybridization
pattern can be visualized on an x-ray film (autoradiogram). One can look at
these banding patterns in the normal population and in FSHD families. If there
is a difference or a connection (linkage) of a particular DNA pattern with an
individual with FSHD, as compared to the DNA of an unaffected individual, it is
an indication that the chromosome 4-linked DNA marker used is close to the FSHD
gene.
Once the assignment of the FSHD gene was made to the end of chromosome 4, the
genetic linkage map of the chromosome was expanded in order to identify more
RFLPs which mapped specifically to the long arm of chromosome 4. Chromosomes
are divided into three regions, 1) the short arm (designated as the p arm), 2)
the long arm (known as the q arm), and 3) the centromere (located between the
arms). In addition, when chromosomes are stained with a particular dye, a
banding pattern appears and the chromosomes can be further subdivided into
numerical regions based on this banding pattern. Therefore, the band observed
on the end of the long arm has been labeled the 4q35 band.
As detailed linkage was established, each DNA marker was positioned along the
chromosome using both genetic and physical mapping techniques and highly
sophisticated computer programs. These different approaches help to confirm the
most likely position of the marker along the chromosome. These computer mapping
programs use very complicated statistical formulae which calculate the most
likely position of one marker in regard to others along the length of the
chromosome. A term frequently used is the lod score (likelihood of the odds) to
determine the order of DNA markers in relation to one another. The higher the
lod score the more likely the markers or genes are close to each other, i.e.,
linked on the chromosome.
Using these techniques, each DNA marker was positioned on the long arm of the
chromosome in relation to one another. The eventual result was a detailed map
of this area of chromosome 4 with informative linkage groups spaced regularly
throughout the arm. Various RFLP markers were used to screen members of FSHD
families in an effort to regionally sublocate the gene along the chromosome.
Keeping the order of the markers which had been mapped to the long arm of
chromosome 4 fixed, the lod score is calculated for each possible map position
of the FSHD gene. If the order of the markers was A B C D E, one would test the
possibility that the FSHD gene was between A and B, so the map would look like
A - FSHD- B - C - D - E, etc. until all the possible combinations were tested
and the lod score calculated for each position. Using this multipoint linkage
approach, it was possible to map the FSHD gene to the most distal region of the
long arm of chromosome 4, that is the end of the chromosome known as 4q35.
The very location of this mapping position raised some interesting questions
and difficulties for scientists in the field. On the positive side, it was now
possible to concentrate cloning efforts on one area of the genome (genome is a
collective term used to designate all of the DNA in all of the chromosomes) and
to search for DNA markers which mapped closer and closer to the FSHD gene
itself. The eventual goal being to identify the gene and to isolate RFLPs which
could be used for diagnostic purposes. On the negative side, is the fact that
the ends of chromosomes are notoriously difficult to clone and expression of
genes in this area may be affected by their proximity to the end of the
chromosome.
As probes were identified which mapped close to the FSHD gene, it was now
possible to ask questions as regards the heterogeneity of the gene. Is there
more than one gene responsible for the FSHD phenotype such as appears to be the
case in Alzheimer's Disease? Does it appear that there is more than
one mutation which can cause FSHD such as in Duchenne's Muscular
Dystrophy? Or is a single mutation responsible for the disease such as in
Sickle Cell Anemia? One could also start to answer questions in families in
which it appears the disease occurred as the result of a spontaneous
mutation--was it in fact a new mutation or a variation in the expression
(penetrance) of the FSHD gene? As we progress close to mapping the gene itself
more detailed and exciting questions about the disease mechanism can be
addressed and hopefully answered.
The telomere (end of the chromosome) in the 4q35 region contains repetitive,
heterochromatic (non-gene coding) DNA. The telomeric ends of the chromosomes
are also known to be "hot spots" of recombination, meaning that
these regions of the genome could tend to be areas of genetic mutation. In the
late 80s a very tightly linked marker for Huntington's Disease was
isolated which mapped to the end of the short arm of chromosome 4. Extensive
genetic maps were developed for this area of the chromosome, but it took
several years of intensive effort by a consortium of scientists before a
flanking marker was isolated (i.e., one which maps to the other side of the
gene). This flanking marker enabled researchers to bracket the DNA on either
side of the Huntington gene and eventually led them to the gene itself. FSHD
researchers are still searching for this flanking marker of the FSHD gene and
will need to identify more chromosome 4-linked markers and FSHD families in
order to achieve this goal. One of the most important research tools for any
geneticist is the availability of DNA from affected families. Without this
resource, it would be impossible for scientists to identify and eventually
isolate the FSHD gene.
As the genetic map of the 4q35 region was expanded, an EcoRI RFLP was
identified using a probe called p13E11. This particular marker showed tight
linkage to the FSHD gene. This EcoRI RFLP is observed in the normal population
and detects DNA fragments of greater than 28 kb (kilobases) in length. However,
in patients with FSHD, the DNA fragment detected using this probe is measurably
smaller than 28 kb in length. This smaller EcoRI-generated fragment has been
shown to be linked to the disease state in FSHD families and has also been
observed in sporadic cases of FSHD. There have been a small number of cases
studied in which there appears to be a recombination event that has occurred
between the FSHD gene and the small EcoRI fragment. This seems to indicate that
although this marker is very close to the gene it is not within the gene
itself.
Within this EcoRI-generated fragment, a family of 3.3kb repeats has been
identified. This 3.3kb family has been shown to map to the telomere (very end)
of the long arm of chromosome 4. It has been postulated that the type of
repetitive, heterochromatic DNA associated with telomeric regions of
chromosomes play an important role in chromosome packaging and/or the
expression of adjacent gene sequences. One could imagine that this
FSHD-associated repeat serves an important role in gene expression, perhaps it
acts as a buffer between active and inactive DNA. Therefore, a deletion in this
area could result in an effect in which the expression of the active FSHD gene
is diminished or eliminated as a result of a change in the size of the 3.3kb
repeat fragment. In fact, an increasing body of evidence supports this
hypothesis.
First, the majority of familial and sporadic cases of FSHD show linkage to a
gene on 4q35. With few exceptions, there is tight linkage between the
appearance of the smaller EcoRI fragment and the disease state. Second, there
is some correlation between the size of the deletion and the severity of the
disease. The smaller the EcoRI fragment, the more severely affected the
patient. This observation may not hold up for every case or even within
families themselves, but it is suggestive of a possible mechanism for the
disease phenotype and the variable penetrance within and among families. Third,
because these telomeric regions of chromosomes are "hot spots"
for recombination, it would not be surprising that there would be a high rate
of spontaneous mutations resulting in the FSHD phenotype. It has been estimated
that as many as 10 percent of the new cases of FSHD represent new mutations. In
an area of high recombination, there might also be observed a high degree of
variability in the expression of the disease. One could easily postulate that
once the chromosome structure had been altered as a result of a deletion, the
DNA in this area could be "destabilized" or more easily modified
by other genetic factors.
Despite rapid progress in the area of FSHD research, much work and many
questions remain to be answered. It appears that while the 3.3 repeat family
may strongly influence expression of the FSHD gene, it is not within the gene
itself. The deletions seen in this repeat family may be responsible for the
variability observed in the FSHD phenotype or they may merely modify FSHD gene
expression. Several FSHD families do not appear to demonstrate linkage to 4q35
and a few individuals with the chromosome 4-linked form of FSHD do not
demonstrate this small EcoRI fragment. Whether these patients are expressing a
different form of FSHD or if they have another disease showing the FSHD
phenotype remains to be seen. Until the goal of FSHD gene isolation has been
achieved, the elucidation of the solutions to these questions will remain
unsolved.
______________________
Evelyn Devine Gage received her Ph.D. in Pathobiology from Columbia University,
New York. Her areas of research have been Down's Syndrome and
Gaucher's Disease. Dr. Gage worked at the New York Institute for Basic
Research and taught at Mt. Sinai Hospital, New York. She currently resides in
Lexington, Massachusetts.
It has been more than five years since the chromosomal localization of the FSHD
gene was identified by researchers in Leiden. Three years ago, deletions
associated with FSHD were reported by researchers in Leiden and London. These
breakthroughs and others have considerably narrowed the region in which to
search for the FSHD gene.
To date, no group has announced the identification of the FSHD gene and FSHD
researchers are rapidly developing new theories and lines of investigation as
more information emanates from the search for the gene.
Funding from the National Institutes of Health is approximately $425,000 for
the fiscal year 1995 to date. Additionally, the funding amount from the
Muscular Dystrophy Association is about $400,000 for the fiscal year 1995 to
date down from $633,000 for the fiscal year 1995.
Several molecular genetics research groups are actively searching for the FSHD
gene by identifying and studying genes that map near the FSHD associated
rearrangements. They include: Dr. Michael Altherr (Los Alamos National
Laboratory), Dr. Giancarlo Deidda (Institute of Cell Biology, CNR, Rome,
Italy), Dr. Luciano Felicetti (Institute of Cell Biology, CNR, Rome, Italy),
Dr. Denise Figlewicz (University of Rochester), Dr. Rune Frantz (University of
Leiden, The Netherlands), Dr. Jane Hewitt (University of Manchester, U.K.), Dr.
Robert Lyle (University of Manchester, U.K. and Research Institute of Molecular
Pathology, Vienna, Austria), Dr. Kathy Mathews (University of Iowa), Dr. Meena
Upadhyaya (University of Cardiff, U.K.), Dr. Kiichi Arahata (National Institute
of Neuroscience--NCNP, Tokyo, Japan), Sara Winokur (University of
California, Irvine), and Dr. Barbara Weiffenbach (Collaborative Research
Division, Genome Therapeutics Corporation, Waltham, MA).
Several research groups are pursuing clinical studies. Dr. Robert Griggs and
Dr. Rabi Tawil (University of Rochester) and Dr. Jerry Mendell are conducting
natural history studies on FSHD as well as drug therapy trials. Dr. Shapiro
(Massachusetts General Hospital, Boston, MA) and Dr. Preston (Brigham &
Women's, Boston, MA) are conducting High Protein Diet and Exercise
Therapy (HPET) trials. Lastly, researchers studying correlations between
phenotype and genotype are: Dr. Robin Fitsimmons (Moorefields Eye Hospital,
London, England) and Dr. Valery Kazakov (Pavlov's Institute, St.
Petersburg, Russia).
The 1995 FSHD meeting sponsored by the MDA was held in conjunction with the
45th annual meeting of the American Society of Human Genetics in Minneapolis,
MN on October 25, 1995. The following abstracts appeared in the American
Journal of Human Genetics . . .
1. Genetic aspects of Facioscapulohumeral Muscular Dystrophy. (Padberg et
al., Nijmegan, The Netherlands)
2. Interphase structural analysis of the FSHD region on 4q in relationship to
the nucleolar organizing regions, (Bengtsson et al., University of California,
Irvine and Los Alamos National Labs, Los Alamos, NM)
3. The putative break point and sequences for the DNA rearrangements in 4q35
linked facioscapulohumeral muscular dystrophy (FSHD), (Lee et al., National
Institute of Neuroscience, Tokyo, Japan).
4. Analysis of genotype-phenotype correlation in Facioscapulohumeral muscular
dystrophy (FSHD), (Figlewicz et al., University of Rochester, NY)
5. Evidence that anticipation in 4q35 facioscapulohumeral muscular dystrophy
may be modifying the age of onset as controlled by D4F104S1 fragment size: a
gene interaction?, (Lunt et al., Bristol Children's Hospital, Bristol,
U.K.)
6. Physical mapping evidence for a duplicated region on chromosome 10qter
showing high homology with the facioscapulohumeral muscular dystrophy (FSHD)
locus on chromosome 4qter, (Deidda et al., Institute of Cell Biology, CNR,
Rome, Italy)
7. Utilization of cosmid sequences in the facioscapulohumeral muscular
dystrophy (FSHD) gene region to identify candidate genes for FSHD, (Weiffenbach
et al., Genome Therapeutics Corp., Waltham, MA).
From the President
"But there was no information, and so we continued
"And arrived at evening, not a moment too soon
"Finding the place; it was (you may say) satisfactory."
--T.S. Eliot,
Journey of the Magi
Once again, I hope that this newsletter will bring information and optimism to
all of you. Much is happeningÉ
Several interesting molecular genetics research papers have been written in the
past few months. Deidda, Felicetti et al, (Rome, Italy), Lyle, Hewitt et al,
(Manchester, England), Arahata, Lee et al. (Tokyo, Japan) have written on the
FSHD associated repeats. The study of the FSHD associated repeats is at the
forefront of molecular genetics and numerous theories are being put forth as to
what role the repeats play in FSHD. Of equal importance is the ongoing work in
other laboratories to isolate the FSHD gene. The debate is simple: are we
dealing with a chromosome mechanism or a gene? The answer is still unknown.
Why is this encouraging? There are now a multitude of theories and a multitude
of scientists committed to the debate on FSHD. Five years ago, who would have
dreamed that there would be so many excellent scientists and researchers
committed to solving FSHD? This sentiment is shared by Evelyn Gage, Ph.D., in
her overview of FSHD research that appears in this edition of the FSH Watch.
Dr. Gage's article has been written for the non-scientist and it is my
hope that it integrates the more technical sections of this newsletter for our
non-technical readers.
In other areas of FSHD research, many exciting developments are occurring.
Clinical trials are being conducted with drug therapies, and protein and
exercise therapies. Clinicians and researchers are working hard to understand
how all of the new aspects of the disease (phenotype) might relate to its
genetic origin (genotype). A mouse model is being pursued as a model for FSHD.
These developments, too, are encouraging.
In the last six months, the Society has facilitated connecting grant agencies,
researchers and clinicians. We have been able to facilitate much communication
among the professional community. One example of how we are facilitating this
process is in helping scientists get the materials they need to complete the
next phase of research by asking our affected readership to consider donations
to brain and tissue banks. Conversely, we have worked with the researchers to
get the correct FSHD tissue collection criteria for the staffs of the brain and
tissue banks. (Please see page 17.) I hope you will give this request the
consideration it deserves. We are in a position to effect change.
Featured in this edition is the FSHD patient brochure. At its inception, the
FSH Society had the goal of a patient brochure containing useful information
for anyone concerned with FSHD. After many long hours and hard work on the part
of Stephen J. Jacobsen, Ph.D., the Scientific Advisory Board and Board Members
of the FSH Society, we now have an informative, concise, thorough and
competently prepared patient brochure. Additionally, we have started work on an
FSHD brochure for the medical professional and have submitted grants to help
finance its publication. This is more encouraging progress.
A grant has been submitted to the National Institutes of Health (NIH) for a
joint NIH/FSH Society Symposium on FSHD in November, 1996. The prospect for the
grant is excellent and NIH continues to show concern and support for FSHD
research. Earlier this year, we successfully submitted congressional testimony
with congressional backing. This is another significant achievement. Although
it has been a tough year in Washington, the NIH budget is holding ground. The
concern and increasing interest of all parties involved is encouraging. We are
making inroads. We are making FSHD visible.
People are hearing about us. Our membership is growing steadily nationally and
internationally. Our Internet page has 40 to 80 log-ins daily. People are
networking along all lines and aspects of the disease. Noteworthy is the
success of FSHD support groups. With credit to Mary Redick, the Infantile FSHD
group is proof of the good work we are all doing. Also, note the continuing
family tradition of service to individuals with FSHD by Marilyn Meisel, head of
the New York group. Our profile on Marilyn shows the connection between the
founders of the Muscular Dystrophy Association (MDA) and FSHD. People are
coming forward after a long silence and we are empowering people.
As always, I had hoped to be able to announce the discovery of the FSHD gene in
this issue. In light of the above, I ask you to stay optimistic and positive in
the face of adversity and challenge. With so much research, information and
knowledge available to us now, we need to continue. In the words of T.S. Eliot,
we will be arriving, not a moment too soon, finding the place and it will be
satisfactory.
Lastly, please support the work of the Society by contributing and donating
services. We need your contributions and we ask you to ask your friends to
support us. We have much work to do and we need capital to continue our vision.
We look forward to 1996 and the NIH/FSH Symposium. It will only happen with
your support.
--Daniel Paul Perez, President
FSH Society, Inc.
Acknowledgements
Members
As of September 15, 1995 we welcome the
following new members. Their names are printed
with their permission.
Joann Ayers--Connecticut
Rabbi & Mrs. Kenneth Block--Maryland
Stephen Bradford--California
Ms. Claudine H. Brown--New Mexico
Manuel Cabral--Toulouse, France
Mr. & Mrs. Peter C. Carrothers--Texas
Jeff Crispin--California
Linda A. Gonzales--New Mexico
Rosanna Mossa--Etobicoke, Canada
Mrs. Margaret D. Powers--New York
Jeanne M. Rulli--Pennsylvania
Alfred E. Slonim, M.D.--New York
Suzanne Stekly--Massachusetts
Mrs. Danielle Wong--Mauritius, IndianOcean
In Honor of Jessica Ryley
David Smith--Ohio
Timothy Smith--Texas
Condolences
The FSH Society extends its condolences to the family of James Chin II and
to his many friends on their loss, and expresses its appreciation to those who
have contributed to the Society in his name to honor his memory.
Contributors
Mr and Mrs. Demetrio Beatrice--New York, in memory of James Chin II
Bobbie Emerson--Massachusetts
Mr. & Mrs. Joseph P. Endres--Ohio, inmemory of Bernadette
Endres
Mr. & Mrs. Louis Struppa--New York, in memory of James Chin II
Daralyn, Lee and Susi, Billing Department, Boston Home Medical, in honor of
Ann Starkey
Thank You!
The FSH Society wishes to acknowledge the
following for their contributions to our efforts.
Mary Grady, Manchester, NH for New England FSH Support Group meeting
summaries.
Sheila Landsman, Lexington, MA for volunteering time in our office.
Laura and Roman Litovsky, Newton, MA for assistance with translation of our
Russian correspondence.
Ardeth Millner, Lexington, MA for transcribing meeting notes
Robert F. Smith, Harwich, MA for videotaping presentations on FSHD.
Thilmany Division, International Paper for contributing supplies for
membership mail.
Bev and Jim Weyenberg, Kaukauna, WI for membership and newsletter
mailings.
Current Happenings in FSHD Research
It has been more than five years since the chromosomal localization of the FSHD
gene was identified by researchers in Leiden. Three years ago, deletions
associated with FSHD were reported by researchers in Leiden and London. These
breakthroughs and others have considerably narrowed the region in which to
search for the FSHD gene.
To date, no group has announced the identification of the FSHD gene and FSHD
researchers are rapidly developing new theories and lines of investigation as
more information emanates from the search for the gene.
Funding from the National Institutes of Health is approximately $425,000 for
the fiscal year 1995 to date. Additionally, the funding amount from the
Muscular Dystrophy Association is about $400,000 for the fiscal year 1995 to
date down from $633,000 for the fiscal year 1995.
Several molecular genetics research groups are actively searching for the FSHD
gene by identifying and studying genes that map near the FSHD associated
rearrangements. They include: Dr. Michael Altherr (Los Alamos National
Laboratory), Dr. Giancarlo Deidda (Institute of Cell Biology, CNR, Rome,
Italy), Dr. Luciano Felicetti (Institute of Cell Biology, CNR, Rome, Italy),
Dr. Denise Figlewicz (University of Rochester), Dr. Rune Frantz (University of
Leiden, The Netherlands), Dr. Jane Hewitt (University of Manchester, U.K.), Dr.
Robert Lyle (University of Manchester, U.K. and Research Institute of Molecular
Pathology, Vienna, Austria), Dr. Kathy Mathews (University of Iowa), Dr. Meena
Upadhyaya (University of Cardiff, U.K.), Dr. Kiichi Arahata (National Institute
of Neuroscience--NCNP, Tokyo, Japan), Sara Winokur (University of
California, Irvine), and Dr. Barbara Weiffenbach (Collaborative Research
Division, Genome Therapeutics Corporation, Waltham, MA).
Several research groups are pursuing clinical studies. Dr. Robert Griggs and
Dr. Rabi Tawil (University of Rochester) and Dr. Jerry Mendell are conducting
natural history studies on FSHD as well as drug therapy trials. Dr. Shapiro
(Massachusetts General Hospital, Boston, MA) and Dr. Preston (Brigham &
Women's, Boston, MA) are conducting High Protein Diet and Exercise
Therapy (HPET) trials. Lastly, researchers studying correlations between
phenotype and genotype are: Dr. Robin Fitsimmons (Moorefields Eye Hospital,
London, England) and Dr. Valery Kazakov (Pavlov's Institute, St.
Petersburg, Russia).
The 1995 FSHD meeting sponsored by the MDA was held in conjunction with the
45th annual meeting of the American Society of Human Genetics in Minneapolis,
MN on October 25, 1995. The following abstracts appeared in the American
Journal of Human Genetics . . .
1.Genetic aspects of Facioscapulohumeral Muscular Dystrophy. (Padberg et
al., Nijmegan, The Netherlands)
2.Interphase structural analysis of the FSHD region on 4q in relationship to
the nucleolar organizing regions, (Bengtsson et al., University of California,
Irvine at Los Alamos National Labs, Los Alamos, NM)
3.The putative break point and sequences for the DNA rearrangements in 4q35
linked facioscapulohumeral muscular dystrophy (FSHD), (Lee et al., National
Institute of Neuroscience, Tokyo, Japan).
4.Analysis of genotype-phenotype correlation in Facioscapulohumeral muscular
dystrophy (FSHD), (Figlewicz et al., University of Rochester, NY)
5.Evidence that anticipation in 4q35 facioscapulohumeral muscular dystrophy
may be modifying the age of onset as controlled by D4F104S1 fragment size: a
gene interaction?, (Lunt et al., Bristol Children's Hospital, Bristol,
U.K.)
6.Physical mapping evidence for a duplicated region on chromosome 10qter
showing high homology with the facioscapulohumeral muscular dystrophy (FSHD)
locus on chromosome 4qter, (Deidda et al., Institute of Cell Biology, CNR,
Rome, Italy)
7.Utilization of cosmid sequences in the facioscapulohumeral muscular
dystrophy (FSHD) gene region to identify candidate genes for FSHD, (Weiffenbach
et al., Genome Therapeutics Corp., Waltham, MA).
Researchers
Sao Paulo, Brazil
Researcher(s):M. Rita Passos-Bueno
Address:Departmento de Biologia, Instituto de Biociencias, Universidade de Sao
Paulo, Sao Paulo, C.P. 11461, CEP 05422-970 S.P. Brazil
Interest(s): Clinical and occupational
Bristol, England
Researcher(s):Peter Lunt, Philip Jardine
Address:Institute of Child Health, Bristol Royal Hospital for Sick Children,
St. Michael's Hill, Bristol BS2 8BJ, England
Interest(s): Molecular genetics and clinical
Cardiff, England
Reseachers:Peter Harper, Meena Upadhyaya
Address:Institute of Medical Genetics, University of Wales College of
Medicine, Heath Park, Cardiff CF4 4XN, England
Interest(s):Molecular genetics
Manchester, England
Abstract:
Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant
neuromuscular disorder that maps to human chromosome 4q35. FSHD is tightly
linked to a polymorphic 3.3-kb tandem repeat locus, D4Z4. D4Z4 is a complex
repeat: it contains a novel homeobox sequence and two other repetitive sequence
motifs. In most sporadic FSHD cases, a specific DNA rearrangement, deletion of
copies of the repeat at D4Z4, is associated with development of the disease.
However, no expressed sequences from D4Z4 have been identified. We have
previously shown that there are other loci similar to D4Z4 within the genome.
In this paper we describe the isolation of two YAC clones that map to
chromosome 14 and that contain multiple copies of a D4Z4-like repeat. Isolation
of cDNA clones that map to the acrocentric chromosomes and Southern blot
analysis of somatic cell hybrids show that there are similar loci on all of the
acrocentric chromosomes. D4Z4 is a member of a complex repeat family, and PCR
analysis of somatic cell hybrids shows an organization into distinct
subfamilies. The implications of this work in relation to the molecular
mechanism of FSHD pathogenesis is discussed. We propose the name 3.3-kb repeat
for this family of repetitive sequence elements. Please see pages 14 and 15 for
bibliography.
Researcher(s):Jane Hewitt, Robert Lyle, Lorraine Clark, Elizabeth M.
Valleley
Address:Laboratory of Human Molecular Genetics, Department of Cell and
Structural Biology, 3.239 Stopford Building, University of Manchester, Oxford
Road, Manchester M13 3PT, England
Boulogne, France
Researcher(s):Yves Rideau
Address:Unite Duchenne de Boulogne, Centre Hospitalier Universitaire, BP 577,
86021 Poitiers Cedex, France
Interest(s):Orthopedic Surgery (Scapula Fixation), Corrective Procedures for
FSHD.
Paris, France
Researcher(s):Michael Fardeau
Address:Institut National de La Sante et , de le Recherche Medicale, 17 Rue du
Fer-a-Moulin, 75005 Paris, France
Interest(s):Clinical
v v v
Update:We are glad to be added on the list of laboratories working in the
field of FSHD. Our major goal is to provide, in our non-profit university
genetic center, the best service for molecular diagnosis.
Researcher(s):Jean-Claude Kaplan
Address:Laboratoire de Biocheme Genetique, Hospital Cochin, 123 Bouldvard De
Port-Royal, 75014, Paris, France
Interest(s): Molecular genetics
Rome, Italy
Abstract:
P13E-11, a probe (D4F104SI locus) derived from chromosome 4q35, detects
EcoRI-rearranged fragments less than 28 kb in both sporadic and familial cases
of facioscapulohumeral muscular dystrophy (FSHD). These fragments are smaller
than those observed in healthy individuals. The interpretation of Southern
blots is complicated by the fact that p13E-11 reveals two pairs of polymorphic
alleles, one 4q35-specific and the other unlinked to 4q35, that sometimes
overlap each other. We cloned a non-4q35 35-kb fragment not related to the
disease from a sporadic FSHD patient of Italian origin. Haplotype analysis and
in situ hybridization experiments showed that this fragment was located on the
10qter region. Restriction mapping of the 10qter clone, when compared with the
4q35 fragment, indicates a similar arrangement of KpnI tandemly repeated units
and flanking sequences. However, 4q35 and 10q26 EcoRI clones can be
distinguished by restriction analysis with SfiI and StyI. This observation
could be exploited for future application in the field of molecular diagnosis
and genetic counseling. In addition, the isolation of two 10q26 cosmid clones
(D10S1484 and D10S1485) from a human genomic library and the construction of a
detailed physical map, spanning about 40kb, showed that the structural homology
extended upstream of the EcoRI sites, suggesting that a duplicated FSHD locus
resided in the subtelomeric region of the long arm of chromosome 10. We cannot
exclude the involvement of the duplicated locus in the molecular mechanism of
the disease and in the genetic heterogeneity of FSHD syndromes. Please see
pages 14 and 15 for bibliography.
Researcher(s):Giancarlo Deidda, Luciano Felicetti
Address:Istituto di Biologia Cellulare, CNR, Viale Marx 43, 1-00137, Rome,
Italy
Interest(s):Molecular genetics
Tokyo, Japan
Abstract:
Clinical Genetic Analysis and Cloning of the FSHD Gene. Facioscapulohumeral
muscular dystrophy (FSHD) is a dominantly inherited muscular disorder and the
gene for FSHD has been mapped to the subtelomeric region of chromosome 4q35,
using polymorphic markers including D4S139, D3S163 and D4F35S1 (Wijmenga, 1990,
1991; Upadhyaya, 1990, 1991; Mills, 1992; Sarfarazi, 1992). The probe p13E-11
(D4F104S1) has been subcloned from the cosmid 13E, which contained
homeobox-like sequences (Wijmenga, 1992). Importantly, this probe detects
specific smaller (10-28 kb) EcoRI fragment that cosegregates with the disease.
In most patients with FSHD, deletions of integral copies of the 3.3 kb tandemly
repeated unit (D4Z4) within the EcoRI fragment have been identified (Winokur,
1993; Wright, 1993; van Deutekom, 1993). Thus, the p13E-11 probe is considered
to have an immediate diagnostic value for FSHD, although the probe recognizes
chromosomes other than 4, such as Y.
To examine FSHD-associated DNA rearrangements in the Japanese population, we
performed Southern blot analysis of the genomic DNA, using the p13E-11 and
pFR-1 probes, in over 300 Japanese individuals, including 75 FSHD patients from
43 families. Most of the Japanese FSHD patients (>95%) had specific smaller
(<28kb) EcoRI fragments which cosegregated with the disease. This included
six patients who had severe inflammatory changes in the muscle and patients
with 14 de novo DNA rearrangements. The increased number of necrotic muscle
fibers was paralleled by an increased number of inflammatory cells (r=0.783,
P=0.0001). These results suggest that, in FSHD, inflammatory changes in muscle
are closely related with the intrinsic part of the disease process, and that
the p13E-11 and pFR-1 probes are tightly linked markers of FSHD.
We cloned the FSHD-associated 10kb EcoRI fragments from three severely affected
patients (unrelated). Restriction enzyme maps of the genomic fragments in the
three patients revealed that the 10kb fragments were identical and contained
only one 3.3kb KpnI repeat unit. The 10kb fragments may provide a means of
understanding the molecular details involved at the site of the chromosomal
rearrangements in FSHD. We further sequenced a 3.3kb KpnI repeat unit within
the tandem repeat locus and its upstream 2.5kb HincII/KpnI fragment of the FSHD
gene region. The 3.3kb KpnI unit contained two homeodomain sequences, one
Lsau-like sequence, and several microsatellites. The GC content in the 3.3kb
unit was very high (73%), while it was only 35% in the non-repeated region of
the 2.5kb fragment.
Although we still do not know whether truncation deletion of the D4Z4 region
could produce FSHD directly of indirectly (position effect), we are now
beginning to understand FSHD. In the next step, FSHD gene product (mRNA or
protein, or both) responsible for the disease should be investigated. We thank
Dr. Hideo Sugita (President, NCNP, Japan) for his helpful discussion and
advice. Please see pages 14 and 15 for bibliography.
Researcher(s):Kiichi Arahata, Hideo Sugita, J.H. Lee
Address:Department of Neuromuscular Research, National Institute of
Neuroscience, NCNP, 4-1-1 Ogawa-higashi, Kodiara, Tokyo, 187, Japan
Interest(s):Molecular genetics and clinical
Leiden, Netherlands
Researcher(s):Oebo F. Brouwer
Address:Department of Neurology, University Hospital Leiden, P.O. Box 9600,
2300 RC Leiden, The Netherlands
v v v
Researcher(s):Rune R. Frantz, Nicole Datson, Judith C.T. van Deutekom, Marten
Hofker, Egbert Bakker, Cisca Wijmenga*
Address:Institute for Anthropogenetica, MGC-Department of Human Genetics,
Leiden University
Wassenaarseweg 72, 2333 AL Leiden, The Netherlands
Notes:*Cisca Wijmenga is currently with The National Center for Human Genome
Research, Laboratory of Gene Transfer, National Institutes of Health, Building
4G, Room 3A14, 9000 Rockville Pike, Bethesda, MD 20892
Nijmegen, Netherlands
Researcher(s):George W.A.M. Padberg
Address:University Hospital Nijmegen St Radboud, Department of Neurology,
Reinier Postlaan 4, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands
Interest(s): Molecular genetics and clinical
ST. Petersburg, Russia
Abstract:
We are studying the clinical peculiarities of facioscapulohumeral muscular
dystrophy (FSHD). 142 patients (66 men and 76 women) from 20 autosomal dominant
pedigrees and three families including five sporadic cases were examined by V.
Kazakov. The age of patients ranged from 4 to 85 years, the duration of the
disease from one year to more than 46. Among the 142 patients, 32 from six
pedigrees were examined in 1969 and 24 of them were reexamined, as well as an
additional 51 patients from six old (25 men) and eight new (26 men) pedigrees
(total of 75) were examined in 1993 according to diagnostic criteria for
FSHD.
Among the 107 patients from 14 pedigrees examined and reexamined in 1969 and
1993, 32 patients were less than 20 years old, 37 were between 20 and 40, and
30 patients were over 40; 28 (26%) patients had a severe form of the disease,
and 67 (63%) were presymptomatic. Additionally, 35 patients from the other six
autosomal dominant pedigrees and three families and five sporadic cases were
examined by V. Kazakov in 1969, but were not reexamined.
Also, the dynamic of the distribution of muscle weakness in 25 probands and
some of their relatives were analyzed using the case histories for 6, 10, 30
and even 40 years.
Besides this, the results received by V. Kazakov in 1969-1970 on analysis of
the patterns of muscle affections in 145 cases taken from the world literature
(108 were hereditary cases, belonging to 62 families and 37 were sporadic) were
used for discussion and conclusion, but these cases weren't included
in the present investigation.
The aim of the investigation was to clarify the pattern of muscle weakness
during the separate phases of FSHD.
In each pedigree and sporadic case the diagnosis of FSHD was supported by
myopathic EMG and normal motor nerve conduction velocity, as well as myopathic
changes on muscle biopsy. Manual muscle strength, trophics, and function of
muscles were examined according to specially developed methods. Mimic muscle
strength and degree of severity of the disease were measured according to the
criteria compiled by V. Kazakov.
A great similarity of clinical manifestations among the members of the
pedigrees was noted. The same muscles and muscle groups were affected in
hereditary and sporadic cases. Clinical variability of phenotypes, namely the
different degree and frequency of affection of the same muscles, reflecting
various phases of the diseases and different expressivities of the mutant gene,
were always in the limits of the identical final phenotype.
Thus, we examined the clinically and genetically homeogeous group of patients
with autosomal dominant descending with a "jump" form of FSHD,
called facioscapuloperoneal dystrophy (FSPD).
Among patients observed we did not come across any cases having the autosomal
dominant gradually descending form of FSHD, called facioscapulolimb dystrophy
(FSLD), in which the upper arm as well as the pelvic and proximal lower limb
muscles get weak earlier than those in the peroneal group (anterior tibial)
muscles.
In FSPD, when the process is progressing, the muscles of the thighs (namely,
posterior groups, but not quadriceps) and then pelvic girdle (namely, gluteus
maximus, but not gluteus medius and iliopsoas) and later to a lesser degree the
upper arms (biceps brachii) are involved. Thus, FHPD (jumping form) in the
latter phase will be presented with facio-scapulo-peroneal-femoro (posterior
group of the muscles)-gluteo (gluteus maximus)-(humeral) phenotype. This is
almost a final phenotype of this muscular dystrophy.
Speaking of FSLD all the gluteal muscles and iliopsoas in the limits of pelvic
girdle are involved, and then when the generalization process goes on muscles
of thighs (namely, quadriceps) and later to a lesser degree the peroneal group
of the shines are involved. Thus FSLD (gradually descending form) in the later
phase will be presented with facio-scapulo-humero-pelvic-femoro-(peroneal)
phenotype. This is almost a final phenotype of this muscular dystrophy.
In both forms (FSPD and FSLD) when the process is progressing the same muscles
of the forearms extensors of hands and fingers), the thenar and hypothenar,
abdomen and trunk can be involved. Yet, in patients with FSPD these muscles as
well as those of the upper arms, as a rule, were involved later and less
severely than in FSLD.
We could not reveal the "pure" FSH and SH phenotypes of muscle
weakness among examined patients. The weakness of upper arm muscles in FSPD
appears when peroneal groups of shin muscles (anterior tibial) were severely
affected. From the other side, the scapuloperoneal phenotype of muscle weakness
with very minimal (or rarely without) affection of facial muscles in the
majority of our observations predominated the clinical picture for a very long
time (on average 11 to 16 years).
In conclusion, we would like to stress that "pure" FSHD does not
exist as a nosological entity. It is merely a syndrome (the special topography
of muscle weakness) which characterizes the initial phase of FSLD, but not the
FSPD itself.
It is quite probable that FSPD and FSLD, which may be differentiated
clinically, are two different diseases connected with a mutation of allelic or
even different genes.
We would like to remark that the point of view discussed herein was first
expressed by V. Kazakov in 1971 in his thesis, and then in 1974 in European
Neurology when Prof. H.E. Kaeser published his work. In 1995 in Muscle and
Nerve, V. Kazakov has offered additional clinical criteria for differential
diagnosis of these two types of muscular dystrophy and, as 23 years ago, V.
Kazakov supposes that these types of dystrophy are distinct genetic entities.
Please see pages 14 and 15 for bibliography.
Researcher(s):Valery M. Kazakov, Dimitry Rudenko
Address:Department of Neurology, Pavlov's Medical Institute, L. Tolstoy Str.
6/8, 197089 St., Petersburg, Russia
Interest(s):Clinical
United States of America:
Davis, CA
Update: Nancy Seyden welcomes your participation in a quality of life study of
individuals with neuromuscular diseases. She can be reached at 916/752-2903 or
TDD/Fax: 916/752-3468 or by mail: Research and Training, Med. PM&R, TB 191,
UC Davis, Davis CA 95616
Dr. Ted Abresch is seeking participants in an internet information study
(see page 18 for details). He is pleased to report that the FSH Society
Bulletin Board at UC Davis has been very active.
Researcher(s):M. Brewer; D.D. Kilmer; R. T. Abresch; S.G. Aitkens; G.T.
Carter; W.M. Fowler; E.R. Johnson; C.M. McDonald; N.J. Wright
Address: Research and Training Center on Neuromuscular Disease, Department of
Physical Medicine and Rehabilitation, University of California, Davis, TB 191.
Davis, CA 95616-8665; and National Institute on Disability & Rehabilitation
Research
Interest(s): Rehabilitation, Occupational and Clinical
Irvine, CA
Researcher(s):Sara T. Winokur; Ulla Bengtsson; John Wasmuth; Michael
Altherr*
Address:Department of Biological Chemistry, University of California, Irvine,
Irvine, CA 92717
Interest(s): Molecular genetics
Notes:*Michael Altherr is currently with the Genomics and Structural Biology
Group, LANL, Los Alamos, NM
Los Angeles, CA
Researcher(s):Stanley F. Nelson
Address:University of California, Room 3256, RNRC, 710 Westwood Plaza, UCLA
Medical School, Los Angeles, CA 90024
Interest(s): Molecular Genetics
Iowa City, IA
Researcher(s):Kathrine Mathews; Brian Shute; Kate Mills; Julie Fedderson;
Holly Bailey; Jeff Murray
Address:Department of Pediatrics, 216 MRC, University of Iowa Hospitals and
Clinics, Iowa City, Iowa 52242
Interest(s): Molecular genetics , clinical and mouse model
Boston, MA
Reseacher(s):David C. Preston
Address:Brigham & Women's Hosptial, 75 Francis Street, Boston,
Massachusetts 02115
Interest(s):Neuromuscular Service
v v v
Researchers:Barbara E. Shapiro, Neurology Service
Address:Massachusetts General Hospital, 15 Parkman Street, Acc #835, Boston,
Massachusetts 02114
Interests: Clinical and nutritional
Waltham, MA
Note:Dr. Weiffenbach is looking for new participants in an ongoing research
study on genetics of FSHD. Please call Dr. Weiffenbach at 617/893-5007 if you
are interested in helping with this study.
Researcher(s):Barbara Weiffenbach, Susan Manning, Zying Liu
Address:Genome Therapeutics, Corp., 1365 Main Street, Waltham, Massachusetts
02154
Interest(s): Molecular genetics
Los Alamos, NM
Researcher(s):Michael R. Altherr
Address:Life Sciences, Group LS 2, M880, Los Alamos National Laboratory, Los
Alamos, New Mexico 87545
Interest(s): Molecular genetics
Rochester, NY
Researcher(s):Robert Griggs; Rabi Tawil; Denise Figlewicz; Lynn Cos; James
Forrester; Michael McDermott
Address:University of Rochester School of Medicine, Department of Neurology,
601 Elmwood Avenue;, P.O. Box 673, Rochester, New York 14642
Interest(s): Molecular genetics and clinical
Updates: Robert C. Griggs, M.D., Chair, Neurology: We are currently embarking
on a pilot trial of albuterol and anticipate continuing our search for nontoxic
agents that have at least a theoretical basis for trial in FSHD. We continue to
recruit subjects for the study of natural history and anticipate new trials in
the coming year.
Rabi Tawil, M.D., Neuromuscular Disease Center: The University of Rochester
continues to follow our natural history patients on at least an annual basis
with our local patients coming every six months.
We completed a small trial using prednisone on eight of our patients to test
for improvement in strength and changes in the rate of muscle protein
synthesis, and will compare them to eight FSH patients who did not take
prednisone. The results so far indicate that there is no improvement in
strength after 12 weeks of prednisone.
We are currently treating a pilot group of approximately 10 patients divided
between the University of Rochester and Ohio State University with albuterol.
The patients will take the medication for three months and we will then compare
their muscle strength pre- and post-drug. We hope to have preliminary results
by the end of 1995 and, if promising, will open the trial to the entire
population of FSH patients.
Durham, NC
Update:Our efforts have focused on determining the location of the
non-chromosome 4 gene responsible for FSHMD. Our studies to date indicate that
FSHMD in up to 50 percent of families is caused by a gene other than the one on
chromosome 4. Currently, we have excluded about 80 percent of the genome as a
possible location for this yet to be discovered gene.
Researcher(s):Margaret Pericak-Vance, John R. Gilbert, Marcy Speer
Address:Duke University Medical Center, 227D Bryan Research Building, P.O. Box
2900, Durham, North Carolina 27710
Interest(s):Molecular genetics
Note: The Center for the Study of Inherited Disorders (CSINDS) at Duke
University Medical Center is actively soliciting the cooperation of families
for participation in on-going research in FSH muscular dystrophy. The purpose
of the study is to identify all chromosomal locations of the disease gene(s).
Ideally, families would be composed of three or more living generations with
multiple members in each generation and should not have participated with
another institution in similar studies. Please call Jeffrey M. Stajich at
919/286-6515 or send him an e-mail message at:
stajich@dnadoc.mc.duke.edu
Columbus, OH
Researcher(s):Jerry Mendell
Address:Department of Neurology, Ohio State University, Columbus, Ohio
43210
Interest(s): Clinical
Marburg, West Germany
Researcher(s):Manuela Koch
Address:Institut for Humangenetic der, Philipps-Universitat, Bahnhofstr. 7A,
D-3550 Marburg, West Germany
Interest(s): Molecular genetics
Research Bibliography
1994 n n n
Bengtsson U, Altherr MR, Wasmuth JJ, Winokur ST, (1994). High resolution
fluorescence in situ hybridization to linearly extended DNA visually maps a
tandem repeat associated with facioscapulohumeral muscular dystrophy
immediately adjacent to the telomere of 4q. Hum Mol Genet 3(10):1801-5.
Brouwer OF, Padberg GW, Wijmenga C, Frants RR, (1994). Facioscapulohumeral
muscular dystrophy in early childhood. Arch Neurol 51(4):387-94.
Cacurri S, Deidda G, Piazzo N, Novelletto A, La Cesa I, Servidei S, Galluzzi
G, Wijmenga C, Frants RR, Felicetti L, (1994). Chromosome 4q35 haplotypes and
DNA rearrangements segregating in affected subjects of 19 Italian families with
facioscapulohumeral muscular dystrophy (FSHD). Hum Genet 94(4):367-74.
Deidda GC, Cacurri S, La Cesa I, Scoppetta C, Felicetti L, (1994). 4q35
molecular probes for the diagnosis and genetic counseling of
facioscapulohumeral muscular dystrophy [letter]. Ann Neurol 36(1):117-8.
Fitzsimons RB, (1994). Facioscapulohumeral dystrophy: the role of inflammation.
Lancet 344(8927):902-3.
Goto K, Sugihara R, (1994). [A case of facioscapulohumeral muscular atrophy
presenting unusual squatting gait, associated with tongue atrophy and
sensorineural hearing loss]. Rinsho Shinkeigaku 34(11):1157-61 (Published in
Japanese).
Hewitt JE, Lyle R, Clark LN, Valleley EM, Wright TJ, Wijmenga C, van Deutekom
JCT, Francis F, Sharpe PT, Hofker M, Frants RR, Williamson, R, (1994). Analysis
of the tandem repeat locus D4Z4 associated with facioscapulohumeral muscular
dystrophy. Hum Mol Genet 3(8) 1287-1295.
Jardine PE, Koch MC, Lunt PW, Maynard J, Bathke KD, Harper PS, Upadhyaya M,
(1994). De novo facioscapulohumeral muscular dystrophy defined by DNA probe
p13E-11 (D4F104S1). Arch Dis Child 71(3):221-7.
Jardine PE, Upadhyaya M, Maynard J, Harper P, Lunt PW, (1994). A scapular onset
muscular dystrophy without facial involvement: possible allelism with
facioscapulohumeral muscular dystrophy. Neuromuscul Disord 4(5-6):477-82.
Lunt PW, (1994). Report of the sixth International Workshop on
Facioscapulohumeral Muscular Dystrophy: San Francisco, 11 November 1992; and
current guidelines for clinical application of DNA rearrangements at locus
D4S810. Muscular Dystrophy Group of America. Neuromuscul Disord 4(1):83-6.
Masuda Y, Hayashi M, Obara H, (1994). [Sevoflurane anesthesia for a patient
with facioscapulohumeral muscle dystrophy]. Masui 43(4):580-3 (Published in
Japanese).
Personius KE, Pandya S, King WM, Tawil R, McDermott MP, (1994).
Facioscapulohumeral dystrophy natural history study: standardization of testing
procedures and reliability of measurements. The FSH DY Group. Phys Ther
74(3):253-63.
Sanchez-Alcon MD, Perez Garrigues H, Vilchez J, Casanova B, Morera C, (1994).
[The study of deafness in patients with facioscapulohumeral dystrophy].
Estudio de la hipoacusia en los pacientes con distrofia facioescapulohumeral.
Acta Otorrinolaringol Esp 45(2):79-82 (Published in Spanish).
Tawil R, McDermott MP, Mendell JR, Kissel J, Griggs RC, (1994).
Facioscapulohumeral muscular dystrophy (FSHD): design of natural history study
and results of baseline testing. FSH-DY Group. Neurology 44(3 Pt 1):442-6.
Weiffenbach B, Dubois J, Manning S, Ma NS, Schutte BC, Winokur ST, Altherr MR,
Jacobsen SJ, Stanton VP Jr., Yokoyama K, et al, (1994). YAC contigs for 4q35 in
the region of the facioscapulohumeral muscular dystrophy (FSHD) gene. Genomics
19(3):532-41.
Wijmenga C, van Deutekom JC, Hewitt JE, Padberg GW, van Ommen GJ, Hofker MH,
Frants RR, (1994). Pulsed-field gel electrophoresis of the D4F104S1 locus
reveals the size and the parental origin of the facioscapulohumeral muscular
dystrophy (FSHD)-associated deletions. Genomics 19(1):21-6.
Winokur ST, Bengtsson U, Feddersen J, Mathews KD, Weiffenbach B, Bailey H,
Markovich RP, Murray JC, Wasmuth JJ, Altherr MR, et al, (1994). The DNA
rearrangement associated with facioscapulohumeral muscular dystrophy involves a
heterochromatin-associated repetitive element: implications for a role of
chromatin structure in the pathogenesis of the disease. Chromosome Res
2(3):225-34.
Kazakov VM, (1994). Affection of mimic muscles, simulating damage of facial
nerve in patients with facioscapulohumeral muscular dystrophy. Eur Arch
Otorhinolaryngology Suppl: S96-S101.
1995 n n n
Altherr MR, Bengtsson, U, Markovich RP, Winokur ST, (1995). Efforts toward
understanding the molecular basis of facioscapulohumeral muscular dystrophy.
Muscle Nerve Suppl 2:S32-8.
Arahata K, Ishihara T, Fukunaga H, Orimo S, Lee JH, Goto K, Nonaka I, (1995).
Inflammatory response in facioscapulohumeral muscular dystrophy (FSHD):
immunocytochemical and genetic analyses. Muscle Nerve Suppl 2:S56-66.
Bakker E, Wijmenga C, Vossen RH, Padberg GW, Hewitt J, van der Wielen M,
Rasmussen K, Frants RR, (1995). The FSHD-linked locus D4F104S1 (p13E-11) on
4q35 has a homologue on 10qter. Muscle Nerve Suppl 2:S39-44.
Brouwer OF, Padberg GW, Bakker E, Wijmenga C, Frants RR, (1995). Early onset
facioscapulohumeral muscular dystrophy. Muscle Nerve Suppl 2:S67-72.
Deidda, G., Cacurri, S., Grisanti, P., Vigneti, E., Piazzo, N. and Felicetti,
L. (1995). Physical mapping evidence for a duplicated region on chromosome
10qter showing high homology with facioscapulohumeral muscular dystrophy locus
on chromosome 4qter. Eur. J. Hum. Genet. 3: 155-167.
Furukawa T, (1995). Neurogenic FSH muscular atrophy. Muscle Nerve Suppl
2:S96-7.
Griggs RC, Tawil R, McDermott M, Forrester J, Figlewicz D Weiffenbach B,
(1995). Monozygotic twins with facioscapulohumeral dystrophy (FSHD):
implications for genotype/phenotype correlation. FSH-DY Group. Muscle Nerve
Suppl 2:S50-5.
International Symposium on Facioscapulohumeral Muscular Dystrophy, Clinical and
Molecular Genetic Aspects of the Disease. Kyoto, Japan, July 10, 1994. (1995).
Muscle Nerve Suppl 2:S1-109.
Lee JH, Goto K, Matsuda C, Arahata K, (1995). Characterization of a tandemly
repeated 3.3-kb KpnI unit in the facioscapulohumeral muscular dystrophy (FSHD)
gene region on chromosome 4q35. Muscle Nerve Suppl 2:S6-13.
Lee JH, Goto K, Sahashi K, Nonaka I, Matsuda C, Arahata K, (1995). Cloning and
mapping of a very short (10-kb) EcoRI fragment associated with
facioscapulohumeral muscular dystrophy (FSHD). Muscle Nerve Suppl 2:S27-31.
Lunt PW, Jardine PE, Koch M, Maynard J, Osborn M, Williams M, Harper PS,
Upadhyaya M. (1995). Phenotypic-genotypic correlation will assist genetic
counseling in 4q35-facioscapulohumeral muscular dystrophy. Muscle Nerve Suppl
2:S103-9.
Lunt PW, Jardine PE, Koch MC, Maynard J, Osborn M, Williams M, Harper PS,
Upadhyaya M, (1995). Correlation between fragment size at D4F104S1 and age of
onset or at wheelchair use, with a possible generational effect, accounts for
much phenotypic variation in 4q35-facioscapulohumeral muscular dystrophy
(FSHD). Hum Mol Genet 4(5):951-958.
Lyle R Wright TJ Clark LN Hewitt JE (1995). The FSHD-associated repeat,
D4Z4, is a member of a dispersed family of homeobox-containing repeats, subsets
of which are clustered on the short arms of the acrocentric chromosomes.
Genomics 28:389-97.
Padberg GW, Brouwer OF, de Keizer RJ, Dijkman G, Wijmenga C, Grote JJ, Frants
RR, (1995). On the significance of retinal vascular disease and hearing loss in
facioscapulohumeral muscular dystrophy. Muscle Nerve Suppl 2:S73-80.
Padberg GW, Frants RR, Brouwer OF, Wijmenga C, Bakker E, Sandkuijl LA, (1995).
Facioscapulohumeral muscular dystrophy in the Dutch population. Muscle Nerve
Suppl 2:S81-4.
Kazakov VM, Rudenko DI, (1995). Clinical variability of facioscapulohumeral
muscular dystrophy in Russia. Muscle Nerve Suppl 2:S85-95.
Mathews KD, Mills KA, Bailey HL, Schelper RL, Murray JC. (1995). Mouse
myodystrophy (myd) mutation: refined mapping in an interval flanked by homology
with distal human 4q. Muscle Nerve Suppl 2:S98-102.
Mathews KD, Rapisarda D, Bailey HL, Murray JC, Schelper RL, Smith R, (1995).
Phenotypic and pathologic evaluation of the myd mouse. A candidate model for
facioscapulohumeral dystrophy. J Neuropathol Exp Neurol 54(4):601-6.
Mills KA, Mathews KD, Scherpbier-Heddema T, Schelper RL, Schmalzel R, Bailey
HL, Nadeau JH, Buetow KH, Murray JC, (1995). Genetic mapping near the myd locus
on mouse chromosome 8. Mamm Genome 6:278-80.
Upadhyaya M, Maynard J, Osborn M, Jardine P, Harper PS, Lunt P, (1995).
Germinal mosaicism in facioscapulohumeral muscular dystrophy (FSHD). Muscle
Nerve Suppl 2:S45-9.
van Deutekom JC, Hofker MH, Romberg S, van Geel M, Rommens J, Wright TJ, Hewitt
JE, Padberg GW, Wijmenga C, Frants RR, (1995). Search for the FSHD gene using
cDNA selection in a region spanning 100 kb on chromosome 4q35. Muscle Nerve
Suppl 2:S19-26.
Wijmenga C, Dauwerse HG, Padberg GW, Meyer N, Murray JC, Mills K, van Ommen GB,
Hofker MH, Frants RR, (1995). Fish mapping of 250 cosmid and 26 YAC clones to
chromosome 4 with special emphasis on the FSHD region at 4q35. Muscle Nerve
Suppl 2:S14-8.
Zatz M, Marie SK, Passos-Bueno MR, Vainzof M, Campiotto S, Cerqueira A,
Wijmenga C, Padberg G, Frants R, (1995 Jan). High proportion of new mutations
and possible anticipation in Brazilian facioscapulohumeral muscular dystrophy
families. Am J Hum Genet 56(1):99-105.
Goto K. Lee JH, Matsuda C, Hirabayashi K, Kojo T, Nakamura A, Mitsunaga Y,
Furukawa T, Sahashi K, Arahati K, (1995). DNA rearrangements in Japanese
facioscapulohumeral muscular dystrophy patients; clinical correlations.
Neuromuscul Disord 5(3):201-8.
Washington Update
On Oct. 1, the federal government's new fiscal year will begin. Rarely
has a fiscal year begun with such uncertainty. Several important pieces of
legislation affecting millions of persons with neurological disorders remain in
political gridlock.
First, the budget for the National Institute on Neurological Disorders and
Stroke, part of NIH, remains undecided. The generous increase engineered by
Labor HHS Subcommittee Chairman John Porter (R-IL) was not matched by the
Senate subcommittee in spite of the Senate's support for a budget
amendment earlier in the year restoring funding for NIH.At stake is $16 million
as a conference committee of the House and Senate will try to reconcile their
budget figures in the coming weeks. Compounding the problem are riders attached
to the House bill which the Senate struck, especially one involving research on
fetal tissue.
Second, the Republicans are expected shortly to release details of their
proposal for changing Medicare. Congressional Democrats are waiting in the
wings, remembering how the Republicans attacked Clinton's health care
plan in 1993-94. It is true that the Republicans need to make major cuts in
Medicare if they are to come close to meeting their promise to cut taxes and
balance the budget. A major lesson of the Clinton struggle appears to be
forgotten: people do not like dramatic changes in how they receive health care
services.
The direction of the Republican efforts are not clear. Earlier in the summer,
there was much talk of vouchers for the elderly to purchase health care on the
private market. This idea met with little enthusiasm. Next, it was financial
incentives to join managed care plans. This may well be part of the eventual
proposal but it does not appear enough to reach the savings the Republican
leadership promised. The alternatives are going to be higher premiums by
well-to-do elderly, higher copayments and deductibles, and lower reimbursement
to physicians and hospitals.
Whatever happens, Congressional Democrats are likely to vigorously fight the
proposal. The White House has been giving some mixed signals about Medicare
reform.
A sleeper issue is Medicaid reform. Medicaid finances the bulk of government
supported nursing homes and health care services to both the poor and the
disabled. A large number of Medicaid recipients have neurological, mental or
addictive disorders. The legislation changing Medicaid from an entitlement
program to a block grant to the states is currently bogged down over issues of
how to allocate payments to the state. The bigger issue may not arise for some
time after passage, i.e., will Medicaid continue to pay for nursing home and
other health services for persons with disabilities?
--Morgan Downey,
General Counsel, FSH Society
New Director at NIAMS
On August 1, 1995, Stephen I. Katz, M.D., Ph.D., was appointed Director of the
National Institute of Arthritis and Musculoskeletal and Skin Disease (NIAMS).
In his letter of August 24, 1995, to the FSH Society, Dr. Katz states,
"I view my appointment as a tremendous challenge and rare opportunity to
help set research priorities and policies that address the chronic and often
disabling diseases with which the institute is concernedÉI view
organizations such as yours as important voices for individuals who are
affected with the diseases with which NIAMS is concerned and for the scientists
in our many fields."
(Note: NIAMS currently funds an FSHD research grant.)
Society for Neuroscience Presents Decade of the Brain Award
On May 16, 1995, the Society for Neuroscience (SFN) presented its sixth annual
"Decade of the Brain" award to Representative John Porter
(R-Ill). The award pays tribute to an individual in Congress who has made an
outstanding contribution to the advancement of brain research. The Decade of
the Brain was initiated in 1990 through a congressional resolution aimed at
providing an impetus for this vital area of biomedical research.
Porter, who serves as Chairman of the House Appropriations Subcommittee that
oversees funding for the National Institutes of Health (NIH), has distinguished
himself as the leading congressional champion of biomedical research. SFN
president, Dr. Carla Shatz, praised Congressman Porter for vigorously making
the case that "health care reform should not simply be about how to pay
medical bills, but how to prevent and cure disease through medical
research."
The FSH Society presented testimony in March 1995 to Chairman Porter to support
research and increase funding for FSHD research in The National Institutes of
Health.
Brain and Tissue Banks for Developmental Disorders
The Brain and Tissue Banks for Developmental Disorders at the University of
Maryland in Baltimore and the University of Miami are tissue resources
established to further research aimed at improved understanding, care and
treatment of developmental disorders. The Brain and Tissue Banks were funded by
the National Institute of Child Health and Human Development to serve as
intermediaries between people who wish to have tissue donated for research upon
the time of their death and the researchers who need this tissue for their
vital work.
The Banks have set up a National Registry of donors so that information
necessary for the rapid recovery of tissue at the time of a donor's
death is available to us. It is very important to register in advance. In order
for tissue to be viable for research, retrieval must be enacted within eight,
or at most 24-hours after death. Time is therefore of the essence and without
some advance planning the Banks may find it impossible to retrieve tissue.
The Banks can work with families and individuals from all areas of the United
States. Please consider registration with the Banks nearest you. It is
important, however, to register with only one Bank.
If you are interested in becoming a registered donor, or if you have any
questions or concerns regarding the donation process, please contact Sally
Wisniewski, Project Coordinator, at 1-800-847-1539. This number is answered on
a 24-hour basis so that we are able to respond swiftly to emergencies. You may
leave a message at any hour, and we will respond as soon as possible. All
inquiries are important to us, and no question is too small.
Thank you for taking the time to consider the possibilities offered to humanity
through the great gift of tissue donation. Internet site:
gopher://gopher.btbank.ab.umd.edu:1070
University of Maryland
Department of Pediatrics, Room 10-035 BRB
655 W. Baltimore Street
Baltimore, MD 21201-1559
1-800-847-1539 FAX: 410/706-0020
e-mail: btbumab@umabnet.ab.umd.edu
H. Ronald Zielke, Ph.D., Director
Sally Wisniewski, B.A., Project Coordinator
University of Miami
Department of Neurology (D 4-5), Room
427A Fox Building
1550 NW 10th Avenue
Miami, FL 33136
1-800-59-BRAIN, FAX: 305/547-6970
Stuart A. Stein, M.D., Director
Elsa Robinson, R.N., Project Coordinator
Access to FSH Society Electronic Bulletin Board
In cooperation with the University of California,
Davis, Division of Physical Medicine and Rehabilitation, we have an FSH Society
electronic bulletin board that is accessible via the Internet.
Access to the bulletin board can be made through either Telnet or the World
Wide Web, which are essentially two different ways of routing your call. Telnet
provides the easiest access and simply requires that you follow the directions
of your local area service provider to Telnet to our address at
medpmr.ucdavis.edu. This will, in essence, ring the computer at the other end
of the line. To get the computer to answer, you must type bbs at the log-in
prompt, and then fsh at both the user ID prompt, and the password prompt.
Reaching our computer through the World Wide Web (WWW) requires a direct
Internet connection or a service which provides an Internet web browser. For
users with a direct connection, a web browser like Netscape or Mosaic, will
allow access to our page. The command to connect to a WWW page is usually Open
Location or Open URL. After issuing this command, type in
http://medpmr.ucdavis.edu. At the
log-in prompt, type bbs and then fsh at both
the user ID and password prompts.
Once you have gained access to the bulletin board, a menu will offer you
several choices. There is a read only menu that contains information and news
from the FSH Society. There is also a read/write bulletin board where you can
read messages left by others or post your own message for others to read. The
bulletin board will be monitored and inappropriate or misleading messages will
be removed. There is also "chat", which allows you to carry on a
live conversation with anyone in the world who is also in chat at the same time
as you are. This may be very useful for support groups or individuals to hold
meetings, and access to the "room" can be restricted or open.
After giving the bulletin board a try, let us know what you think by leaving a
message for the sysop (system operator).
--William R. Lewis, III, M.D., Cardiologist, Cardiovascular Medicine,
School of Medicine, University of California, Davis, is an FSH Society board
member and member of the Scientific Advisory Board of the FSH Society.
Research Project on WWW/Internet Seeks Volunteers
Hi. My name is Ted Abresch. I work for the Research and Training Center for
Neuromuscular Diseases at the University of California at Davis. I am
interested in investigating ways to improve dissemination of disability-related
information to consumers and service providers. I am in the process of
developing a handbook on disabilities with the intent of providing users with
information and referral phone numbers regarding various aspects of
disabilities. The goal of the project is to provide consumers with information
about health care, independent living, financial assistance, transportation,
laws and rights, access, employment, education, new technologies, psychological
and social issues, parenting issues, recreational issues, and research on the
world wide web.
I am trying to develop an electronic handbook on disabilities that presents
information that is most needed by the consumers and is easy to use. To build
this system, I need your help. First, I need to know what your experience is
using the internet and world wide web. I also need to know what you would like
to see in a web site, what web sites you like, what you do not like about the
web, and how you would like information presented. I am also looking for
subjects and information that people would like to see in this handbook.
You can help me by volunteering to become part of an electronic participatory
action research group that would analyze existing web sites and help me develop
a new system.
If you are interested, please contact Ted Abresch, Department of Physical
Medicine and Rehabilitation, School of Medicine, UC Davis, Davis CA 95616. Or
you can e-mail me at rtabresch@ucdavis.edu.
Surfing with FSHD!
In 1981 I was diagnosed with FSHD (facioscapulohumeral dystrophy). I
immediately had the urge to speak to someone in my age group who had this
dreadful disease. I was living in New York City at the time and thought surely
I would be able to find at least one person among 8 million with FSHD. I
contacted the Muscular Dystrophy Association and they were not able to locate
anyone.
Then along came Internet. When I moved to California last year, I discovered
America Online (AOL) and the Equal Access Cafe with a muscular dystrophy room
on Friday nights at 9 p.m. EST. The first night I was in the room I met Karen
Johnsen, board member of the FSH Society and Ms. Wheelchair Maryland, as well
as three other women in my age group with FSHD. I thought that this was the
greatest thing since cherry pie! I have been in contact with these women for a
while now and it has given me a better understanding of my disease. We had our
first on-line chat in a private room and it was really great.
When you are on line, you have a screen aid and a profile that gives
information about the person you are chatting with, i.e., geographic location,
age, marital status, interest, hobbies, etc. As I am a curious soul (and
usually don't bother chatting with people who don't have
profiles), I went into KJay1's profile and discovered that she was
from Bowie, Maryland, and ran a support group. I was beside myself. I know this
woman--well, not exactly. I am originally from Maryland and my mother put
my name on Karen Johnsen's Mid Atlantic FSH Society Support Group
mailing list. My mom, who has lunched with Karen and her mother, always
encouraged me to attend Karen's group when I visited her from New
York. The time never seemed to be right. I had seen Karen in a videotaped
segment of an MDA Telethon and thought how much she reminded me of myself. I
had the pleasure of meeting Karen in person at the Ms. Wheelchair America
Pageant in California this August. It's a small world!
AOL is beta testing the Worldwide Web and I have been able to post a message on
the bulletin board. Two other FSHDers contacted me, one of whom had never met
or spoken with anyone with FSHD. If you have AOL, use keyword disabilities to
find the Equal Access Cafe. Anyone can contact me at Jillpf@aol.com. Karen
Johnsen may be contacted at KJay1@aol.com. Happy surfing!
--Jill Fleisher
Jillpf@aol.com
Palo Alto, CA
Let's Communicate!
Don Burke, Alice Springs, Australia welcomes your contact along the
superhighway. His e-mail address is: 74244.2577@compuserve.com
Don was profiled in our Spring 1995 FSH Watch and would enjoy your contacting
him down under! Inadvertently, we omitted Don's e-mail address in the
last newsletter.
Pen Pal Wanted!
Craig is 14-years-old, and would like to hear from others with FSHD. You can
reach him at:
Craig Eynon, PO Box 1152, Mead, WA 99021. 509/466-1956
Meet Marilyn Meisel
Marilyn Meisel, leader of the Tri-State (New York, New Jersey and Connecticut)
FSH Society Support Group in Fresh Meadows, New York, brings a wealth of
experience to individuals with FSHD (facioscapulohumeral muscular dystrophy).
Marilyn's family has a history of FSHD going back several generations.
Family members have FSHD in varying degrees.
In the late 1940s, Marilyn's parents, Belle and David Meisel, driven
by a desire to bring muscular dystrophy (MD) out of the shadows, founded the
Muscular Dystrophy Association (MDA) to get funding for research and develop a
sense of community for those with MD. A doctor put a number of his MD patients
in touch with the Meisels and the MDA was born. Meetings were held in the
Meisel home in Queens and later in the Manhattan office of Paul Cohen, another
founder who also has FSHD. An automobile was raffled off in the first
fundraising event circa 1950. One of the early members had a relative who
worked in the entertainment business with Jerry Lewis and got him involved.
A few years after getting the MDA off the ground, the Meisels and others
founded another organization, the National Foundation for Neuromuscular
Diseases. This organization focused more on providing services to those with
neuromuscular diseases. "My parents' goal for this organization
was to do something for children with neuromuscular diseases. The Foundation
took them to ball games and parties just so the kids could enjoy
themselves."
In keeping with the family tradition, Marilyn saw a need for a sense of
community among FSHD patients. After reading the FSH Watch, Marilyn contacted
Carol Perez, FSH Society Director, to begin an FSHD support group in the
Tri-State area. Founding the Tri-State Group of the FSH Society continues her
family tradition of community involvement. The Tri-State group, based in
Marilyn's home in Queens, New York, meets once every two months to
discuss what is happening in FSHD and share information, problems and
solutions. The group, now 14 families, is growing as the FSH Society expands in
the New York area.
"Respecting confidentiality, the FSH Society, physicians and clinics
inform people with FSHD about the Tri-State FSH Society Support Group.
Interested people are put in touch with us and members share information among
themselves," Marilyn said. She added that the biggest bonus of having
formed the Tri-State FSH Society Support Group is "meeting with other
people who understand what we go through on a daily basis living with FSHD. We
don't sit around and whine about our troubles. We share information
and talk about what is happening. Many people with MD, especially FSHD, have
never met another person with their disease, so getting together is really
helpful."
Marilyn emphasizes that many group members work and are active in their
community. Marilyn is a supervisor with the Child Welfare Administration in New
York City. In her spare time, Marilyn enjoys theater, cooking, reading and
watching tennis with her "neurotic dog." Marilyn's
brother, who lived to age 38, had an early onset of FSHD and was severely
disabled. Although by the age of 16 he required a wheelchair, her brother
graduated from college and went to work for the City of New York full time as
an accountant. With acquaintances and coworkers pitching in when he needed
assistance, his resilience was an example of how people with FSHD can be
productive in our society. "We know it's (FSHD) there, but most
of us choose to ignore it and go on with life."
Marilyn Meisel is the product of a long line of family members who make a
difference in our world. Professionally and personally, she is caring and
giving. And, fortunately for the FSH Society, she has followed the family
tradition by joining our organization and founding the Tri-State FSH Society
Support Group. The tradition has come full circle with group meetings in her
home under Marilyn's leadership, hard work and to her credit. To
Marilyn's delight, the FSH Society, which was founded by clinicians,
researchers and families, is consistent with the Meisel family tradition: to
educate, advocate and support research in FSHD.
--Marilyn Meisel and
Mary J. Field
IFSHD National Network Launches New Initiatives
The response to the FSH Society's formation of the Infantile
Facioscapulohumeral Dystrophy (and early onset) (IFSHD) has been very positive.
In just six months, we have heard from nearly a dozen families, one from as far
away as the Netherlands. We have seen that we are not alone and that we share
so many similar experiences, challenges, and opportunities. We are delighted to
have this network up and rolling as we continue to learn and grow together.
One common need is that of information and education. The majority of families
feel that there exists a great void in availability of literature to address
this. The Society is interested in surveying your needs and experience to
accumulate information on early onset and IFSHD. We have identified a number of
families affected with early onset and IFSHD. With your assistance, we may be
able to supply answers to many unanswered questions.
We have had a wonderful suggestion to form a pen pal network for our children.
Anyone interested may contact Carol Perez or me for the name, age, and address
of those involved. Please let us know if you would be interested in receiving
correspondence. Once again, I would like to thank those who have offered
support and acceptance of the IFSHD network. You have all touched my heart. I
would like to invite any of you who have not yet responded to do so.
--Mary Redick, Coordinator, IFSHD Network, W11149 County Road M, River
Falls, WI 54022, 715/425-5302
FSH Groups Welcome New Members
The Mid Atlantic FSH Support Group, New England FSH Support Group and Tri State
(New York Area) FSH Support Group offer the unique opportunity to meet others
and share information and support on FSHD issues.
Meetings* are generally held every other month on Sunday afternoons, covering
topics specific to FSHD. The groups are fortunate to have leading researchers
and clinicians present the current genetic and clinical information.
Experts address nutrition, exercise and coping strategies specific to FSHD.
Individuals, family members and professionals concerned with FSHD are welcome
to attend. There are two groups now forming in Pennsylvania, the Philadelphia
FSH Support Group and the South Central Pennsylvania FSH Support Group.
Please call Carol Perez, FSH Society Director, East Coast Office, 617/860-0501,
with any questions or interest in forming a local group, telephone network or
pen pal group. In order to preserve confidentiality, the FSH Society will
contact members and inform them of groups in their area. We have requests to
form groups in San Diego, San Francisco and Los Angeles, CA; Denver, CO; Palm
Beach, FL; New Orleans, LA; Kansas City, MO; Rochester, NY. Information about
support groups and networks is published in the FSH Watch.
*Groups meet in accessible locations.
Mid Atlantic FSH Support Group:
Karen Johnsen
12203 Foxhill Lane
Bowie, MD 20715
301/262-0701
Call Karen Johnsen for December open discussion meeting date and location.
Karen Johnsen has led the Mid Atlantic FSH Support Group that includes
Maryland, Virginia, Washington DC, Delaware and Pennsylvania since 1990. The
group alternates presentations and open discussion. On October 15, 1995, guest
speaker, Allison Auclair, Disabilities Option Consultant and group member
presented "Practical Solutions in Coping with FSH and the Department of
Rehabilitation Services, Insurance, Physicians, School Systems, etc.,
etc.!"
New England FSH Support Group:
Carol A. Perez
Lexington, MA 02420
617/860-0501
Meeting: Dec. 3, 1995 and Feb. 4, April 14, June 2, 1996
Since 1989, Carol Perez has facilitated the New England FSH Support Group that
covers Connecticut, Maine, Massachusetts, New Hampshire, Rhode Island and
Vermont and meets at the Days Inn, 19 Commerce Way, Woburn MA from 1 to 3:30
p.m. The December meeting is tentatively scheduled at the Days Inn. Please call
to confirm all meeting locations. Presentations are followed by an informal
social hour. Guest speaker, Jacqueline Dobson, OT, consultant, discussed
"Options and Resources for Independence and Accessibility" at the
October meeting.
Tri State (New York) FSH
Support Group:
Marilyn Meisel
Fresh Meadows, New York
718/357-5079
Call Marilyn Meisel for meeting dates and location.
The Tri State (New York Area) FSH Support Group members come from New York, New
Jersey and Connecticut and meet in Queens, New York. Marilyn Meisel, profiled
in this newsletter, established this group in 1994. On Sept. 17, 1995, the
group met for an open discussion of FSHD concerns.
South Central Pennsylvania FSH
Support Group:
Renae Beeker
Hanover, PA
717/632-4803
Call Renae Beeker for meeting date and location.
The South Central Pennsylvania FSH Support Group, coordinated by Renae Beeker,
welcomes your participation. As a member of the Mid Atlantic Support Group,
Renae, a nurse, provides experience and personal knowledge to this forum.
FSH Local Networks:
Colorado:Duanne Dotson, 303/426-9180
4140 W. 74th Ave.
Westminster, CO 80030
Kansas and Oklahoma:
Richard Snow, 316/251-7663
402 Cheyenne
Coffeyville, KS 67337
International FSH Group Updates
As of this edition, the FSH Society has links to FSH Groups in England, France
and the Netherlands. Their Coordinators and updates on activities are listed
below. The French and Dutch Coordinators are fluent in English.
England:Mr. Robin Brown
FSHMD Support Group
1 Hobart Close
Whetstone
London
N20 OTT
England
Phone: 081 361 0089
FranceMs. Catherine LHeureux-Rouslin (fluent in English)
16, Rue du Parc Royal
75003 Paris, France
Phone: (H) 42 74 14 65
Mr. Daniel Mennetret
17, rue Jules Michelet
92170 Vanves, France
Phone: (H) 40 95 17 95
NetherlandsMr. Albert Gielis (fluent in English)
International Contact FSHD working group
C. Beerninckstraat 102