In Honor of Jessi Pease:

In Honor of Jessica Ryley:

In Memory of Alex Kanter:

In Memory of Bernadette Burke:

In Memory of Sadie Cohen:

Condolences

Contributors

Thank You! The FSH Society wishes to acknowledge the following for their contributions to our efforts.

Let's Communicate!

Web Pals Wanted!
Greetings from OZ, I'm Ray, and I've got FSH, too. I'm in Melbourne Australia and I'd like to hear from you. The e-mail address is: rrev@webnet.com.au Cheers (or something)!!!
Mr. Ray Jordan
86 Barry Street
Reservoir
Victoria 3073
Australia

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

Genetic Testing for FSHD

In the last issue of the FSH Watch, an article was featured which detailed the progress which has been made in the search for the FSHD gene. The gene has still not been isolated, however, the EcoRI polymorphism which was linked to FSHD in affected individuals and families has recently been utilized to confirm the diagnosis of FSHD and also to predict the presence of FSHD both prenatally and presymptomatically. Diagnostic and prenatal testing for many genetic disorders has been an available procedure for several years. As gene products and DNA segments associated with a disorder are identified, tests are developed which allow the diagnosis or confirmation of the presence or absence of a genetic disease.

The type of test which is used for diagnosis depends on the nature of the disease. For example, a chromosomal disorder such as Down's Syndrome or Turner's Syndrome can be confirmed in an individual using a blood sample or skin biopsy by the presence of a portion of a specific chromosome or an entire chromosome. Prenatally these disorders can be diagnosed by testing samples obtained via amniocentesis or chorionic villa skin biopsy. In metabolic genetic disorders in which the gene product has been identified, a variety of tests have been developed which measure the level of the relevant enzyme or metabolite using an assortment of human tissues. Tay-Sach's Disease can be diagnosed from human tears as well as from blood, skin and hair samples. For other human genetic diseases, in which the DNA defect has been identified but not the gene product itself, blood samples or skin biopsies are required. As the Human Genome Project progresses, an enormous array of human diseases are falling into this latter category. In the case of FSHD, neither the DNA sequence nor the gene product responsible for the disease has been identified. However, recent developments in the search for the FSHD gene have identified a DNA polymorphism which appears to be tightly linked to the disease in most individuals and which has opened the window to diagnosis and prenatal testing in some FSHD families.

In order to explain the utility of this type of linkage information, it is important to understand some of the background involved in the development of the genetic test. It is also equally important to appreciate the limitations of this test-not all FSHD families are candidates for diagnostic testing. It is also critical to remember that gene testing of any kind in which there is diagnostic confirmation available but no treatment or cure at present presents both the patient and the diagnostician with many more and ethical delimmas.

An EcoRI restriction polymorphism associated with the chromosome 4 marker p13E-11 was identified which mapped to the long end of chromosome 4. Usually the size of the DNA fragments which are observed when human DNA is probed using this marker are between 50 and 300 kb in length. A deletion in this area of the chromosome has been observed which results in DNA fragments smaller than 35 kb in length. This deleted DNA has been linked to the presence of FSHD in most, but not all, FSHD families.

The diagnostic usefulness of this p13E-11 marker is limited by several factors. First, this marker, although it is tightly linked to the FSHD locus may not be within the gene itself. Second, while the majority of FSHD families show linkage of the disease to this marker, approximately 5 percent of "classical" FSHD families are not linked to this region of chromosome 4. Third, while this shortened EcoRI fragment has been demonstrated primarily in FSHD patients, it has also been observed in unaffected individuals. This shortened EcoRI fragment in unaffected individuals maps to the long arm of chromosome 10 (10q) and is not correlated with the presence or absence of this disease. Until recently, the only way to distinguish the chromosome 4 fragments from the chromosome 10 fragments was by linkage analysis using DNA samples from extended family members. Since many FSHD individuals come from families with small pedigrees they could not furnish the required information and would not be candidates for this diagnostic test. A recent report from a research group in Italy (J. Med. Genet., 1996) indicates that a novel test has been developed which eliminates the chromosome 10q fragments thus enhancing the general applicability of the EcoRI p13E-11 test and facilitating the interpretation of the test results. It would be most helpful for FSHD individuals from small families where FSHD is inherited and where linkage analysis discriminating between chromosome 10q and 4q35 markers is not possible.

Despite these difficulties, a research group in The Netherlands using very clearly defined criteria has recently utilized this probe for diagnostic, predictive and prenatal testing in some FSHD families. In order for the marker p13E-11 to be useful in diagnosis of FSHD, the family must meet two important criteria. One, the FSHD phenotype must show tight linkage to chromosome 4q35 and two, the family must demonstrate segregation of the small EcoRI-generated p13E-11 fragment associated with chromosome 4 and not demonstrate association with the chromosome 10 marker. The report mentioned above which would facilitate this discrimination would allow inclusion of additional families for diagnostic testing and enhance the reliability of the test.

Using these guidelines approximately 55 percent of the FSHD families tested met the criteria for diagnostic testing of FSHD. In those families, it was possible to offer presymptomatic and postsymptomatic testing with a fairly high degree of confidence (probability estimates of 99-100 percent). In candidate families, it would be possible to offer prenatal testing if it was desired. Patients with apparent de novo mutations of FSHD can also be analyzed using these parameters.

In the case of the sporadic (de novo) patients, DNA from both of the parents and that of the patient is required. If the small EcoRI fragment is detected in the patient and not in either of the parents, it is possible to confirm the diagnosis of FSHD. In 25 out of the 57 sporadic patients tested, the smaller p13E-11 marker was detected. Sixteen of these cases were proven to be de novo mutations after examination of both parents DNA. In other words, neither parent showed the smaller p13E-11 fragment. It was observed only in the patient's DNA. The FSHD diagnosis in the other nine patients could not be confirmed, either because one of the parents was not available for testing or because they also carried a marker polymorphism whose source could not be ascertained; i.e., whether the marker originated from chromosome 4 or from chromosome 10. Again, a reliable method which could easily ascertain the source of the markers would vastly enhance the reliability and general applicability of this diagnostic test. It is estimated that only about 10 percent of new cases of FSHD are the result of new mutations. Based on the recurrence risk estimates in families with Duchenne's muscular dystrophy, it is calculated that there is also a 10 percent risk for the sibling of a de novo patient with FSHD to be a carrier of the FSHD gene.

This DNA test has also been utilized for the first reported diagnosis of FSHD prenatally. An FSHD patient carrying a well characterized de novo mutation and his spouse requested prenatal testing to be done. The DNA from both of the parents was highly informative-the patient carried the smaller FSHD-related marker and his spouse demonstrated only the larger high molecular weight non-FSHD associated fragments. At eleven weeks of pregnancy, a chorionic villa biopsy was performed and the fetus was shown to carry the FSHD-related marker.

At the present time, the availability of this type of genetic testing for FSHD is severely limited. Only one basic research laboratory in The Netherlands is offering to use the EcoRI-generated p13E-11 fragment as a diagnostic tool and then only for FSHD families with very well defined genetic background and which meet all of the stringent criteria for testing. In addition, if the ratio of eligible families remains constant only about half of the FSHD families would be suitable for predictive testing. Obviously a more widely applicable test is needed, but that will have to await the identification of the gene itself.

-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.

Current Happenings in FSHD Research

It has been four years since the finding that a rearrangement on chromosome 4 showed a strong association with facioscapulohumeral muscular dystrophy. In fact, I think that most researchers believe that this rearrangement, which results in deletion of DNA sequences in patients that are normally present in unaffected individuals, represents the mutation responsible for the disease. The central dogma of molecular biology is predicated on the fact that DNA (the genetic starting block) is transcribed into RNA (the messenger) and translated into protein (the business end of the process). Typically, a mutation detected in the DNA would be expected to reveal itself in the function of the associated protein. For example, a protein might contribute to the structure of a muscle fiber and thereby contribute to the overall muscle's ability to perform work (like walking or lifting). Often mutations alter the normal structure of the protein and prevent it from doing its job. Many researchers have spent long hours in the laboratory looking for messengers that we hoped would be linked to the FSHD associated rearrangement and would allow us to begin to investigate the business of the normal FSHD protein. The situation has been complicated by the presence of the FSHD gene nested amongst a variety of DNA sequences that occur not only in the vicinity of the FSHD gene, but at a number of other locations as well. This has complicated not only the search for the gene but also, the development of diagnostic tests based on the rearrangement.

Nonetheless, the finding of the FSHD associated rearrangement was an important first step in this process. Had the subject of our investigations been a typical genetic disorder we would have simply reached into the geneticist's tool kit, pulled out the messenger and identified the associated protein. Unfortunately, FSHD is not typical and little if anything has been simple. In spite of intensive efforts in laboratories around the world no bona fide genes had been found in the vicinity of the FSHD associated rearrangement, until now. In an article in the May 1996 issue of the Journal of Human Molecular Genetics, researchers from The Netherlands report finding the first gene known to occur in the vicinity of the FSHD gene. The characterization of the gene called FRG1 for FSHD Region Gene 1, displays the difficulties of working with DNA sequences in the FSHD region. The gene FRG1 has related sequences on ten of the 24 different human chromosomes. The investigators had to go to rather extraordinary lengths to demonstrate that the gene was normally expressed from chromosome 4 near the FSHD associated rearrangement and to evaluate whether chromosome 4 specific expression was altered due to the FSHD associated rearrangement in patients when compared to unaffected individuals. While it is not likely that FRG1 is the FSHD gene itself, it has buoyed the spirits of the scientists by indicating that there are actual protein coding units in the vicinity of the FSHD associated rearrangement. Furthermore, the process by which FRG1 was characterized represents a model by which others, as they are isolated, will be evaluated.

Additional insights into the nature of the FSHD mutation has been published by researchers in Brazil, the United Kingdom, and the United States. In these studies two phenomena have been observed. First is a finding of anticipation in FSHD. This process is often noted as an increase in the severity of the disorder when passed from one generation to the next. While statistically significant, the finding is less clear than in other diseases like myotonic dystrophy or Huntington disease. However, these other diseases have characteristic mutations associated with them and the demonstration of anticipation suggests that certain strategies may be employed to identify the FSHD gene. Second is the finding that the size of the FSHD associated rearrangement is correlated with he severity of the disease. This observation is clouded by variation often observed between siblings carrying the same mutation but again suggests that certain strategies may be employed to facilitate the isolation of the FSHD gene.

Finally, contributions to the arena of diagnostic testing have been made by groups in Italy, Japan and The Netherlands. The Italians and Japanese groups have developed techniques to facilitate testing by clarifying the identification of chromosome 4 specific markers. Pending a publication of the Japanese findings, it may be possible to conduct pre-implantation analysis following in vitro fertilization. The Dutch have presented a paper describing the necessary criteria to conduct testing in familial cases. In short, their criteria are: i) that a sufficient number of family members are available to demonstrate that FSHD is genetically linked to DNA markers from chromosome 4; ii) that within the family the FSHD associated rearrangement falls within a specific size range is linked to FSHD and is not complicated by fragments originating from other locations. In most cases, prenatal diagnosis and disease diagnosis by molecular analysis is untenable.

In conclusion, a number of advances have been made in furthering our understanding of the molecular genetics of FSHD. Of particular importance is the identification of the FRG1 gene that maps near the FSHD associated DNA rearrangement. Routine molecular diagnosis is still beyond the horizon and may first require the identification of the specific gene product responsible for FSHD.

-Michael R. Altherr, Ph.D., Researcher, Life Sciences, GENOMICS, Los Alamos National Laboratory, Los Alamos, New Mexico, is a member of the Scientific Advisory Board of the FSH Society.

Brain and Tissue Banks for Developmental Disorders

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

Researchers

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
Researchers: 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
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

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:
A simple restriction assay for the direct detection of 4q35 rearrangements implicated in facioscapulohumeral muscular dystrophy (FSHD).
The p13E-11 probe has been shown to detect 4q35 DNA fragments ranging in size between 10 and 30 kb in sporadic and familial cases of FSHD. Its use, however, has been hampered by the fact that the probe detects at least two pairs of EcoRI alleles, one derived from the 4q35 region (D4F104SI), the other from 10q26 (d10F104S2). An Italian group working at the Institute of Cell Biology in Rome, Italy (Deidda et al J. Med.Genet, 1996, in press) set up a method of EcoRi-BinI digestion that allows differential cleavage of the KpnI units derived from 10q26, leaving intact the 4q35 pair of alleles. This method greatly facilitates the interpretation of Southern blots obtained from affected and unaffected subjects, with an important improvement in reliability for diagnosis and genetic counseling. The differential restriction will be particularly useful in isolated cases and small FSHD pedigrees, where linkage analysis with 10q26 and 4q35 markers are not feasible. Please see pages 14, 15 and 16 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
Researcher(s): Kiichi Arahata, 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

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

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
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 and Dr. Ted Abresch attended the Conference sponsored by the Center On Disabilities at California State University, Northridge. Ted Abresch, Research and Training Center on Neuromuscular Diseases, gave a presentation titled, "The Disability Times: A World Wide Web Electronic Journal and Resource Center" about a system we have been trying to develop on the electronic highway in response to our research. Our research indicates improved access to information is a major need for individuals with disabilities and their families. We described the development and implementation of a referred electronic journal and resource center. The conference provided many opportunities to learn about the cutting edge of technology. There were a vast number of exhibits, with exhibitors from all over the world. Exhibited at the conference is the reality of today and the dreams of tomorrow. The possibilities to improve people's lives are endless and technology is the key.
We are trying to develop an organized system on the Net for a quality of life study. We can share the information with individuals with disabilities and parents of children with disabilities and provide resource information on how to contact companies. The development of this technology and equipment increases our chances to live independently and to keep abreast of changes in our world.
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; 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
Update: High Protein and Exercise Study (HPET)
Dr. Shapiro and Dr. Preston's findings thus far: five patients have completed the study, although initially approximately 15 patients had enrolled. We are still waiting for 1-2 more patients to be completed. Of those who did not complete the study, some had trouble with tolerating the high protein diet (two patients), some moved, some could not stick to the strict dietary and exercise regimen, and some had other medical illnesses that prevented us from using their data.
As for the quantitative muscle testing, we unfortunately did not see improvement and on the subjective neuromuscular functional scale, the scores did not change much at all. However, on the functional tests that were performed (ambulating 20 feet, walking up and down four steps, arising from supine to standing, arising from a chair, putting on a hospital gown) we did see improvement in most patients except for one task, arising from a chair, where most worsened very slightly. The pulmonary tests did not change much, nor did the CPK (muscle enzyme) levels. We do not have the results as yet of the body fat analysis and some of the other urine chemistries that were done.
So it is kind of a mixed picture, by our preliminary look at the data, with no hard statistical analysis. But, interestingly, the functional tests improved. We would like to look at this a little more closely, and also caution that this was a very small sample, and it is hard to draw large inferences from this data. When we have more analysis completed, we will update you. Researcher(s): David C. Preston
Address: Brigham & Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115
Interest(s): Neuromuscular Service

Researchers: Barbara E. Shapiro, Neurology Service
Address: Massachusetts General Hospital, 15 Parkman Street, Acc #835, Boston, Massachusetts 02114
Interests: Clinical and nutritional

Waltham, MA
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
Update: We have continued to follow patients for the natural history study but the major emphasis has been on therapeutic trials. We continue to perform genetic studies in an effort to locate the gene lesion. A manuscript regarding the decline in muscle strength has been submitted for publishing.
The major portion of the FSH natural history study has been completed and a manuscript describing the results of the study will appear shortly. We have recently finished a small pilot study of the effects of Albuterol on FSH dystrophy. Albuterol is an asthma medication which has also been used illicitly by Olympic athletes to enhance their performance. After 12 weeks of treatment all the patients in the study has a significant increase in their muscle mass. Their strength, however, did not show significant improvement. The same patients will be followed for another three months at which time their strength will be reevaluated. These results were sufficiently encouraging that we have applied for a grant to perform a large controlled study of the effects of Albuterol in FSH dystrophy. If our study is funded, we expect to start enrolling patients in June of July 1996.

Durham, NC
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
Abstract:
This abstract was presented at the American Academy of Neurology Meeting in San Francisco on March 29, 1996 and accepted for the Work-In-Progress session.
The abstract describes the preliminary results of a clinical trial of albuterol, a B2 adrenergic agonist agent usually used in asthma, and FSH dystrophy. The FSH Dystrophy Group, which includes the Ohio State University and University of Rochester, enrolled 11 patients in an open-labeled trial of albuterol. As outlined in the abstract, albuterol resulted in a statistically significant increase in muscle mass as determined by dual energy x-ray absorptiometry )DEXA) testing. Although muscle strength did not improve in these patients, a further trial of longer term and higher dose therapy is planned.
Objectives. To determine the effects of B2-adrenergic agonist on muscle mass in facioscapulohumeral muscular dystrophy (FSHD).
Background. FSHD has been linked to locus 4q35 but neither the gene nor product are known. There is no treatment; previous trials of prednisone have shown no benefit. B2-agonists have numerous effects on muscle biochemistry and function. Two studies have shown that B2-agonists increase strength in normal human subjects, suggesting that they might be beneficial in FSHD.
Design. Eleven adult FSHD patients took sustained-release albuterol (8.0 mg q 12 hrs) for 12 weeks. Muscle mass was determined through dual-energy x-ray absorptimetry (DEXA) at baseline and weeks 3 and 12.
Results. There were no dose-limiting side effects. Total body mass increased in all patients (mean 1.56 kg, p=0.002). Lean body mass (skeletal muscle) increased by a mean of 1.74 kg (p=.00039) while fat declined by .175 kg. These results contrast with a prior study of prednisone in FSHD (Tawil et al, 1995) where increased body mass was due entirely to fat, and lean body mass declined.
Conclusions. Albuterol for 12 weeks increases muscle mass in FSHD. This is the first report of the use of a B2-agonist in a neuromuscular disease and is the first agent to have a positive effect in FSHD. The results suggest a new treatment strategy for FSHD and possibly other neuromuscular diseases as well.
Researcher(s): Jerry Mendell, John T. Kissel
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

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.

Kazakov VM, (1994). Affection of mimic muscles, simulating damage of facial nerve in patients with facioscapulohumeral muscular dystrophy. Eur Arch Otorhinolaryngology Suppl: S96-S101.

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.

1995

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.

Goto K, Lee JH, Matsuda C, Hiraayashi K, Kojo T, Nakamura A, Mitsunaga Y, Furukawa T, Sahashi K, Arahata K. (1995). DNA rearrangements in Japanese facioscapulohumeral muscular dystrophy patients: clinical correlations. Neuromuscular Disorders (1995) 5(3):201-08 Pergamon-Elsevier Science Ltd.

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.

Kazakov VM, Rudenko DI, (1995). Clinical variability of facioscapulohumeral muscular dystrophy in Russia. Muscle Nerve Suppl 2:S85-95.

Kilmer DD, Abresch RT, McCrory MA, Carter GT, Fowler, WM Jr., Johnson ER, McDonald CM, (1995). Profiles of neuromuscular diseases. Facioscapulohumeral muscular dystrophy. Am J Phys Med Rehabil (1995-Sep-Oct) 74(5 Suppl): S131-9.

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.

Matthews KD, Rapisarda D, Bailey HL, Murray JC, Schelper RI, Smith R, (1995). phenotypi and pathologic evaluation of the myd mouse. A candidate for facioscapulohumeral dystrophy. J Neuropath Exp Neur (1995 Jul) 54(4):601-06.

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.

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.

Tawil R Meyers, GJ Weiffenbach B, Griffs RC. (1995). Scapuloperoneal syndromes. Absence of linkage to the 4q35 FSHD locus. Arch Neurol (1995 Nov) 52(11):1069-72.

Upadhyaya M, Osborn M, Maynard J, Altherr M, Ikeda J, Harper PS, (1995). Towards the finer mapping of facioscapulohumeral muscular dystrophy at 4q35: construction of a laser microdissection library. Am J Med Genet (1995 Jun 19) 60(3):244-51.

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.

1996

Bakker E, Van Der Weilen MJR, Voorhoeve E., Ippel PF, Padberg GW, Frants RR, Wijmenga C, (1996). Diagnostic, predictive and prenatal testing for facioscapulohumeral muscular dystrophy; diagnostic approach for sporadic and familial cases. J Med GEnet (1996) 33:29-35.

Deidda G, Cacurri S, Piazzo N, Felicetti L, (1996). Direct detection of 4q35 rearrangements implicated in facioscapulohnumeral muscular dystrophy (FSHD). J Med Genet (1996) 33:361-65.

Tawil R, Forrester J, Griggs RC, Mendell J, Kissel J, McDermott M, King W, Weiffenbach B, Figlewicz D, FSH-DY Group, (1996). Evidence for anticipation and association of deletion size with severity in facioscapulohumeral muscular dystrophy. Ann Neurol (1996) 39:448-452.

Tupler R, Beradinelli A, Barbierato L, Frants R, Hewitt JE, Lanzi G, Maraschio P, Tiepolo L, (1996). Monosomy of distal 4q does not cause facioscapulohumeral muscular dystrophy. J Med Genet (1996):366-73.

Washington Update

This year John Porter, Chairman of the Labor-HHS subcommittee, did an outstanding job in getting an increase for NIH. NIH was one of the very few agencies to see any increase. However, the likelihood that future budgets will contain truly significant new funds for expanded research appears very slight.

Even with the increase in the current appropriations, hundreds of important, scientifically worthy grants for brain research are going unfunded. Yet, there is no political visibility of this crisis. Part of the problem is that the advocates seek more government spending when the political forces are demanding less government spending.

Other efforts to increase NIH funding by imposing taxes on cigarettes or health insurance premiums have been unsuccessful.

The issue is how to create a significant, additional pool of money for funding research on neurological, mental and addictive disorders. The FSH Society is a member of the National Council for Research in Neurological Disorders (NCR). Recently NCR has been exploring one avenue toward this goal.

The NCR concept starts from the premise that any new source of funding must be (a) voluntary, (b) revenue neutral, i.e. not increase the federal deficit, (c) likely to create a sufficiently large pool of funding for brain research to be worth the effort and (d) supplement not supplant appropriations.

NCR is considering a legislative initiative to change the tax code for individual filers which would:

• Allow individuals to reduce their refund or add extra funds to their payment for a trust fund on neurological, mental and addictive disorders research,

• Provide that such a fund would be administered by trustees composed of the directors of institutes at NIH with significant brain research portfolios,

• Prohibit Congress from appropriating less funds than the average NIH appropriation for these institutes for a period of time such as six years.

The proposal is revenue neutral, completely voluntary and does not put current NIH funding at risk.

The concept has received strong support from NCR member organizations. However, many are concerned that it could not remain limited to research on brain disorders but would have to include other disease areas as well. The issue could be fixed but it might become difficult if the proposed system ended up being a laundry list of politically attractive diseases while others were left off entirely.

In addition, there are some very practical problems. First, would taxpayers devote additional monies above and beyond their tax liability to such a fund? Would the community of organizations supporting such a fund direct their attention to getting the public to utilize such a mechanism? Would Congress stick with a commitment to treat such funds as additional to future appropriations or would Congress cut NIH and hope that this fund would make up the difference, leaving the net increase to NIH the same? Other questions abound. However, for NCR, the issue now is not the technical answers to such questions. Rather, the issue is how to focus on creating a large pool of funds to support all the valuable research now sitting unfunded. The FSH Society needs to continue to be part of this ongoing debate.

-Morgan Downey,General Counsel, FSH Society

Our Miracle . . . Caroline

After 15 years of waiting for an answer to the dilemma of how we were going to start our family, my husband and I took a giant leap of faith last year.

From the moment I said "I do" on June 7, 1980, I knew I wanted to be a mom. But there was one huge barrier in my way: A 50 percent chance of passing on FSHD to my child. I agonized over this problem to the point that I could think of nothing else. I watched my friends go through pregnancy after pregnancy as they created their families without a care in the world. And, although Joe and I became God parents to several wonderful children, the void was not filled. When will I have a child of my own to love? As my friends' children grew, I attended lots of birthday parties, I smiled through each party and felt genuinely happy for my friends and their blessings. Afterward, I would get back into my lonely car and drive to my quiet house where I would crawl into bed and cry for hours. My husband suggested that I stop going to these parties, but I was afraid to let my friends know of my misery. It was not just birthday parties that became difficult; the topic of conversation with all my friends always seemed to work its way around to children.

For years, my husband and I waited for genetic testing of this disease or some available treatment. And, although advancements in research were made, it was not going to happen soon. At the age of 37, my biological clock sounded like a gong of our grandfather clock. We needed to make a decision now.

Adoption was a serious consideration and in fact we signed up at the local center for independent adoption. However, halfway through the process, Joe and I confessed to each other that neither of us had overcome the desire to have our own genetic child. So, we resigned from the adoption program.

I first heard about surrogacy from a magazine article on an infertile couple who used the Center for Surrogate Parenting in Beverly Hills to assist them with the birth of their child. The couple used the wife's ovum and the husband's sperm and then placed the embryos in another woman who was pregnant for them. What a bizarre idea, I thought. But, it would avoid the risks associated with my being pregnant, such as increased falling due to the added weight and almost certain bed rest during the last trimester of the pregnancy which could accelerate the weakening of my muscles. Joe and I immediately signed up for an orientation with the Center for Surrogate Parenting. The concept sounded intriguing, although I was a little skeptical about the idea of another woman being pregnant with my husband's baby. I felt a little bit like a failure as a wife since I was now considering asking another woman to perform a basic and fundamental task that was supposed to be reserved for me.

Deciding to use a surrogate was the solution to only half the problem. What about the fact that my ovum carried a 50 percent chance of passing FSHD on to our child? Was I willing to take such a chance? Then I thought, what if I didn't use my ovum? What if I used another woman's ovum? Someone who looked like me and could serve as my substitute? Is this thought too outlandish? Am I so desperate to have a baby that I'm not thinking clearly? One day, during an annual gynecological exam, I mentioned to my doctor my idea of using another woman's ovum. I was delighted when he told me that this was actually quite common and that his office specialized in this process known as ovum donation through in vitro fertilization. He gave me the name of several fertility centers to contact.

I began sharing my idea with several friends to hear their reactions. I explained how this option would allow the child to be linked to my husband whose genetic makeup I knew and trusted and I could personally choose my ovum donor with all the qualities and characteristics that I felt were good substitutes for me. I would have a sense of involvement in the genetic creation of our child, but without the risk of being pregnant myself. Most importantly, our child would not have muscular dystrophy. The overwhelming response from my friends was "go for it"!

One afternoon I met a special friend at Taco Bell for lunch. While we munched on burritos, I told her my plan to use a surrogate and ovum donor to help me have a baby. When I finished my story, my friend looked at me with her brown eyes and endearing smile and said, "I could do this for you...I can have your baby." I choked for a minute on my burrito. I hadn't planned on a friend being pregnant for me. I was going to use someone I didn't know. "You are so sweet," I said, "but that's just too weird." This friend was also a good friend of my husband. In fact, they worked together in the same office. I told her I would consider it, but I really didn't think it would be right.

Over the next couple weeks, I thought a lot about my friend's offer to be pregnant for me. With her as my surrogate, I wouldn't have to worry about another surrogate deciding to try to keep my child once it was born. I knew my friend already had a son and a daughter and had made it very clear that she would not and could not handle any more of her own children. Joe and I had planned on paying someone to be our surrogate anyway, and I knew my friend could really use the money. I could be part of the pregnancy by feeling it kick with my hand and watching its little limbs poke through my friend's big belly as it moved around. I could talk to my baby and watch it grow. Best of all, I trusted my friend and knew she would take care of my precious baby during those nine months. "OK," I told her on the phone one day, "let's do it!"

Convincing our husbands was a little tougher than we thought. Her husband was worried about the added strain her pregnancy would place on their already hectic lives. But eventually they realized that my friend and I had already decided we were going to do this and they had better just get on board.

My friend, my husband, and I set out to find the perfect ovum donor. After a two month search, our beautiful, talented, bright and healthy donor walked through the door of our fertility center. The counselor called us immediately and said, "I have a star for you." Joe and I met her at the fertility center the next day and we loved everything about her. She seemed to like us, too. We then introduced her to our friend. Everyone seemed excited and a little nervous about this incredible project that we were about to undertake. After lots of paperwork, blood tests, fertility drugs and sonograms, the day came for our donor to have ova removed from her ovaries. Joe and I, along with our friend, went to the hospital to be with her during the recovery from surgery. She did great! The hospital mixed the ova and sperm in a Petri dish and two days later we had nine embryos growing. We then drove our friend to the hospital for the embryo transfer. Six of the nine embryos were of sufficient quality to transfer into my friend's uterus. The following ten days were the most anxious of our lives. On the tenth day, my doctor, who had performed the blood test, called me at home. My friend and I were expecting his call and we each had a telephone extension. She and I stared at each other and with hearts pounding as we listened to his words. "Well," he said, "we got the results back from the pregnancy test and it looks like we've got a pregnancy here." Screams and laughter filled the room. My friend and I hugged each other and just could not believe that we had actually nailed it on the first try!

The following nine months were a textbook pregnancy for my friend. All of my expectations for this pregnancy had come true. Placing my hand on my friend's belly, I felt the baby kick and we got to see every detail of our child on a high resolution ultrasound. When the baby was two weeks past due, we decided to take my friend for an evening walk in the park. So, one hot summer night, my friend and her husband and my husband and I walked around the lake in the park until my friend couldn't waddle any longer. We laughed at how silly this must look. Joe held one arm while her husband held the other arm. I paced everyone while riding my scooter. We wondered, does anyone at this park have any idea what an incredible accomplishment this has been for the four of us? We felt so proud of ourselves.

The next night we went into labor and all four of us were in the delivery room. The doctors and nurses, aware of the situation, were excited for Joe and me. At 12:46 a.m. on the following morning, our friend delivered our 8 lb. 6 oz. baby girl. The nurses cleaned our baby and instinctively began to place her on my friend's stomach. "No," said my friend, "hand her to her parents." The nurses placed this tiny, wrapped bundle in my lap and I could feel the tears roll down my cheeks. I looked at my friend lying there and said, "Thank you, Gena. I love you."

Caroline Elizabeth Conron is about to turn one. She has been such a blessing to our family. Out of the six embryos, she is the one who survived. Her strong will and happy spirit is a reflection of her love for life and determination to survive. My friends who now have pre-teen children come by frequently for big hugs from Caroline. She loves people and has a smile and a wave for everyone. I believe she knows how long her mommy and daddy waited for her. She truly is our little miracle.

I share my personal story with you in hopes that it will help someone else who faces the same or similar challenges that Joe and I faced in starting our family. There are several alternative methods available to assist in the creation of families. This is just one of them. -Betsy Conron

The Impact of FSHD in Couple Relationships

It is the intent, that a regular column on the impact of FSHD in couple relations, can address the issues couples face, as well as provide specific suggestions and strategies that would be helpful to those dealing with such issues. It is also hoped that this column will stimulate discussion between couples on the impact FSHD has had on their own marriage. Open communication is key, as it is when these topics and associated feelings cannot be discussed, that the potential for these emotions be be expressed in other ways, such as emotional withdrawal and escalating conflict, increases significantly.

Some topics for discussion include:

• What issues do individuals with FSHD face while dating? Are dating issues different between males and females? When and how should one disclose to a potential mate the diagnosis of FSHD?

• What are the different issues when FSHD is diagnosed before or after marriage? What about the issue of having children. If you have children with FSHD, when and how do you tell them about the disease?

• What about parenting issues, such as the concern some parents have about their grown children leaving home and functioning on their own, versus grown children that are resistant to leaving home?

• What are the issues regarding intimacy and sexuality?

• How do couples plan around the uncertainty of the chronic progression of FSHD?

Your input in the form of questions, comments, or personal experience is welcomed and encouraged. Please address correspondence to Cory Koch, FSH Watch, FSH Society, Inc., 3 Westwood Road, Lexington, MA 02420

-Cory Koch received his M.A. in Marriage and Family Therapy from Pacific Lutheran University, Tacoma, Washington. He is a State Certified Marriage and Family Therapist and Clinical Member of the American Association for Marriage and Family Therapy. His private practice, Couples Clinic, in Seattle, is dedicated exclusively to marital and couples issues. Married 15 years, Mr. Koch, a member of the FSH Society, was diagnosed with FSHD at the age of 16.

World Wide Web/Internet Update

There has been considerable traffic on the internet with over 100 'hits' per day on the web home page maintained by our friends and colleagues at the University of California, Davis, Division of Physical Medicine and Rehabilitation. A hit is simply a connection made with the home page. We are expanding our efforts to transform more of those hits into educational and useful interactions. Currently, the web site contains information submitted by both the FSH Society and the Research Training Center that is germane to disabilities of all types, including muscular dystrophy.

To access the web page, you must connect to the World Wide Web. Most major service provides, i.e., Compuserve, America On-Line, Prodigy, etc., currently provide this access. Once connected, there are several web browsers (software programs) such as Netscape, Mosiac, or Microsoft's Internet Explorer. These browsers are the tools to locate the addressees of the thousands of home pages now available. Whatever software you use, the old home page address is: http://medpmr.ucdavis.edu. If it no longer works the new web home page address is: http://disability.ucdavis.edu.

Once you have reached the web page, you will find back issues of the FSH Watch and the newsletter from the UC Davis Research Training Center. Also, by clicking the appropriate link on the web page, you can transfer to the bulletin board service, bbs. At this location, you can post messages to or read messages from the FSH Society bulletin board.

You can also chat with others by entering a chat room supported by the bulletin board. Unfortunately, this cannot be accessed via the World Wide Web address above. It must be accessed via a telnet session. Once into the telnet service, the site address is either: medpmr.ucdavis.udu or: 128.120.223.215.

Type bbs at the log-in prompt, and then fsh at both the user ID prompt and the password prompt. From there, typing help will guide you through the commands to the chat room. Many people using America On-Line have had trouble running a telnet session, but one individual recently told me that they have found a way to circumvent the problem. If this works, the solution will be posted to the bbs.

Future features of the web page will include a topical database. Besides newsletters of the FSH Society and the Research Training Center, this database will include published scientific articles that will be of interest. The result will be that you can search this database for a subject such as "exercise" and retrieve all the related information on this subject that is in the database. A project of this scope will take many months and will by nature grow over time.

Finally, please submit questions that you have for the scientific advisory board via the bbs. Frequently asked questions will be answered on a monthly basis and posted to the bbs and published in the FSH Watch.

-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.

Internet Fishing

I recently had an interesting experience while surfing the Net. I would like to share it with you all, but first let me introduce myself. My name is Troy Calverley from West Texas. I was diagnosed with Facioscapulohumeral Muscular Dystrophy when I was sixteen. With a B.A. degree in marketing with a minor in management, I am now 28 and, as my father would say, I'm an educated rancher. I work on the family-owned ranch where we raise Brangus cattle. Yes, "Beef, it's what's for dinner" around our house. (Thought I would throw in a little promotion here so I can say I used my marketing degree!)

Back to my adventure on the Net. I frequently use the Internet to keep in touch with a friend of mine in Connecticut. This friend of mine is a pretty crafty fellow and he always tries to catch me off guard. He's quite a joker. This particular day we had decided to use the Internet Relay Chat (IRC). If you are not familiar with the IRC, it allows you to communicate with others on a real time basis. You can actually carry on a conversation by typing in your responses. The IRC has many different topics or rooms you can enter, or you can start a room of your own. My friend and I planned to meet in the FSH room. I signed on and waited for my friend to join me.

Not long after I signed on to the FSH room, I got a message that asked how I was doing and what type of bait I used. This person thought that FSH stood for fishing, obviously. I liked fishing so I thought I would play along for a while until my friend signed on. We talked about the general stuff; swapped fishing stories; a few tall tales about the big fish we caught. This went on for about ten minutes. I still didn't know if this person was a male or female, where he or she lived, how old he or she was, etc., so I asked. I found out the person was a female, 35, single and lived in Iceland.

I started to get a little more interested. I told her I was male, 28, single and lived in Texas, USA. She asked about the U.S. I asked about Iceland. She told me I needed to visit Iceland and go fishing. I thought about getting a little flirtatious, so I replied, "only if she would be my personal guide." To my amazement, she replied she would love to be my personal guide and I could stay with her as long as I desired. I didn't know what to reply back. I started to wonder where my friend was. It had been twenty minutes since he was supposed to sign on.

Suddenly, it hit me like a ton of bricks. This wasn't a lady and she didn't live in Iceland. This had to be my friend, knowing the joker he is. I thought I might as well play along for a while and see how far he would take it. I started asking questions like, "How soft is your bed?" and "What side do you like to sleep on?" I kept getting the appropriate responses. Finally, I replied, "the jig is up. I know who you are, fess up!" No response for a little while, then a reply, "What? I told you who I am."

My friend had done it again. He had gotten the last laugh, didn't even know it and still doesn't, until now.

I had a lot of explaining to do to her, but the offer still stands. So, if you can't reach me on the Net this summer, I'm in Iceland with my personal fishing guide. I may have the last laugh after all!

-Troy Calverley, internet address:troyc@ix.netcom.com

FSH Groups Welcome New Members and Offer New Resources

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 new groups, the Michigan FSH Support Group and the South Central Pennsylvania FSH Support Group.

With pleasure, we announce the formation of the Michigan Support Group in May 1996. Members come from Michigan, Indiana and Ohio and welcome anyone who wishes to attend from any area. Under the leadership of James Partridge and Linda Shain Vanek, they meet near Detroit.

We are pleased to welcome the formation of the South Central Pennsylvania FSH Support Group led by Ranae Beeker. As a member of the Mid Atlantic Support Group, Ranae, a nurse, provides a unique perspective and interesting projects for participants. Ranae looks forward to hearing from you.

Realizing that our network if farflung, we have introduce three new services:

• Meeting notes from the New England FSHD Support Group are posted on the FSH Society Bulleting Board on the Internet at UC Davis.

• Copies of meeting notes from the New England FSHD Support Group are also available from Carol Perez, East Coast Office of the FSH Society.

• Videotapes of selected meetings from the Mid Atlantic FSHD Support Group and New England FSHD Support Group are available on loan ($3.00 postage charge per tape). Tapes currently available include presentations on physical therapy, occupational therapy, massage therapy and a discussion with a physician. Contact Carol Perez, East Coast Office of the FSH Society for further details.

We are grateful to Mary Grady, Karen Johnsen and Robert Smith for making these materials available.

*Groups meet in accessible locations.

Michigan FSH Support Group
James Partridge and Linda Shain Vanek
Call James Partridge at 313/568-6885 for meeting date and location. This May, James Partridge and Linda Shain Vanek initiated the Michigan FSH Support Group which includes Indiana and Ohio to develop a schedule and agenda to meet local needs. James and Linda welcome your call to join them and plan now.

Mid Atlantic FSH Support Group
Karen Johnsen
12203 Foxhill Lane
Bowie, MD 20715
301/262-0701
Call Karen Johnsen for June meeting date and location. There will be a guest speaker.
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. With many new members starting this year, the first three meetings were group discussions. On April 28, Dr. Trent Nichols discussed the relationship of molecular biology and FSHD.

New England FSH Support Group
Carol A. Perez
Lexington, MA 02420
617/860-0501
Meeting: June 2, 1996-Guest Speaker, Connie Roberts, Nutritionist, 1-3:30 p.m.
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 Lahey Clinic Board Room in Burlington , MA from 1-3:30 p.m. Presentations are followed by an informal social hour and discussion. Guest speaker, Dr. Lillian Grayson, discussed "Health and Humor" at the April meeting. Andrew Eycleshymer gave a presentation on exercise and massage therapy in February and Dr. James Russell, Department of Neurology, Lahey Hitchcock Clinic, addressed questions from group members about FSHD at the December 1995 meeting.

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.

Tri State (New York) FSH Support Group
Marilyn Meisel
Fresh Meadows, New York
718/357-5079
Meeting: June 23, 1-3:30 p.m. Guest speaker will be Alfred Spiro, M.D., Neurologist.
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 established this group in 1994. Speakers at the 1995-96 meets were Dr. Roberta Shapiro, Physiatrist, and Dr. Alfred Slonim, Endocrinologist.

FSHD Local Networks
Colorado: Duane 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.

Canada
James & Linda Dobson
Society for Muscular Dystrophy International (S.M.D.I.)
PO Box 470
Bridgewater, Nova Scotia
Canada B4V 2X6
Phone: 902-682-3086
Fax: 902-682-3086
Update: The S.M.D.I. International Newsletter and Access-Able Information are published quarterly. The Winter 1995 newsletter included the FSH Society patient brochure. Thanks to the Dobsons, we are receiving requests from Canada for information about FSHD. The S.M.D.I. Newsletter provides an international forum for disorder/disability information, news and opinion relevant to the field of neuromuscular disorders.

England
Mr. Robin Brown
FSHMD Support Group
1 Hobart Close
Whetstone
London
N20 OTT
England
Phone: 081 361 0089

Mrs. Lorraine Jonas
FSHMD Support Group
2, Hamlyn Close
Edgeware, Middlesex
HA8 8DB
England
Update: Norman and Lorraine Jonas have published the first FSH-MD News Sheet, Issue 1, February 1996. They report that the English group has 150 members. At their 1995 meeting in Oxford, Dr. Peter Lunt reported on progress being made in research, and introduced Dr. Mark Rogers who recently commenced a FSH research project in Cardiff. The newsletter has autobiographical reports on living with FSHD, helpful hints and resources. Their 1996 meeting is scheduled in Oxford in October.

France
Ms. Catherine LHeureux-Rouslin (fluent in English)
16, Rue du Parc Royal
75003 Paris, France
Phone: (H) 42 74 14 65

Mr. Daniel Mennetret
9, route de Preuilh
"Lilaire" 33830 Belin-Beliet
France
Update: The French FSH Group established a cellbank under Professor Jean-Claude Kaplan and completed a survey of medical and health issues for individuals with FSHD in France. Mr. Claude Diaz, Association Francaise Contre Les Myopathies (AFM), is completing the report. More than 60 families are part of the French FSHD cellbank and close to 200 individuals responded to the survey.

Netherlands
Mr. Albert Gielis (fluent in English)
International Contact FSHD working group
C. Beerninckstraat 102
3641 DE Mijdrecht
Netherlands
Phone: (H) 31 2979 86126
(W) 31 2979 73774
Fax: 31 2979 83530
Update:The Netherlands FSHD working group meets annually and publishes four newsletters. At the national FSHD contact day in September, Dr. Judith van Deutekom presented an update on gene location and FSHD. Dr. G. Padberg, Nijmegen, answered questions from FSHD patients about pain, therapy, fatigue, sensitivity to cold temperature, sudden loss of balance and eye problems. In addition, Dr. Padberg explained the use of the "flake" test in prenatal testing with chromosome 4 families.
In the VSN FSHD newsletter, Number 12 November 1995, Dr. G. Padberg's responses to patient questions were published. Dr. Padberg reported that there were about 700 gene carriers in The Netherlands of whom two thirds have symptoms. Therefore, most doctors have no experience dealing with FSHD. Dr. Padberg pointed out that there are 500 neurologists in the Netherlands who see an average of one person with FSHD.

Russia
Tatiana Gorokhova, Information Oficer
SIRIUS
St. Petersberg Branch
Prof. Popova Street 47,
Office 807
171337 St. Petersburg, Russia
Phone: 812 511 2260
Fax: 812 225 2509
Update: SIRIUS is a branch of a newly formed organization aimed at helping children and families with neuromuscular diseases. Their threefold activities are research, recreational programs, and treatment. Currently, they are seeking space for a clinic and welcome information on adaptations, rehabilitation, counseling and current information regarding research on FSHD.

East Coast Update

The challenge ahead is to develop resources to impact directly on research. With all we have accomplished in place, we need to raise monies now to raise visibility in all areas and directly impact the focus on FSHD research. In 1995, the National Institutes of Health (NIH) spent $17 per person with FSHD as compared with $70 for individuals with Charcot-Marie-Tooth disease. ALS research received almost $1,000 per affected person. We need to assure critical work continues. We need to develop our resources to fill in the gaps for those of us living with FSHD every day.

Join us in San Diego and Boston to attend the workshops, presentations, plan the priorities for your organization and meet with your fellow members from all over.

-Carol A. Perez, M.Ed., C.R.C.

West Coast Office Update

Please call with any questions. If possible, put it on your calendar. I look forward to renewing acquaintances and meeting many of you for the first time.

Stephen J. Jacobsen, Ph.D.,, FSH Society, Inc.1507 Traske Road, Encinitas, CA 92024