FSHD is the most prevalent of the nine primary types of muscular dystrophy affecting adults and children

About FSHD

Diagnosis of FSHD Type 1B Non-Chromosome-4-Linked


Facioscapulohumeral Muscular Dystrophy 1B; FSHMD1B

Facioscapulohumeral muscular dystrophy type 1B (FSHD2 or FSHD1B or FSHMD1B) is a much rarer type of FSHD, occurring in several dozen well documented families. FSHD1B is clinically identical to FSHD1A but genetically distinct. FSHD1B is sometimes referred to as FSHD type 2 (FSHD2). The incidence of FSHD1B is not known at this time, but is unlikely to exceed 5% of all cases of FSHD. In FSHD1B the disease is NOT associated with the deletion of 3.3-kb repeats from a chromosomal tandem repeat called D4Z4 located near the end of chromosome 4 at the 4q35-qter location. FSHD1B may be caused by different genes, located on the same or different chromosomes.

The notable difference between FSHD1A and FSHD1B patients is that FSHD1B patients do not have contractions in the 4q35 D4Z4. However, in a similar manner to FSHD1A, in FSHD1B the chromatin structure of the D4Z4 repeats is more open, and at least one 4q35 allele is an A variant. Molecular genetic testing for such patients is available.

FSHD1B is caused the inheritance of two independent genetic variations e.g. by digenic inheritance. In 80% of the FSHD1B patients the disease is caused by heterozygous loss-of-function mutations in the encoding Structural Maintenance of Chromosomes flexible Hinge Domain containing 1 (SMCHD1) gene, a chromatin modifier, brought about by two concurrently occurring genetic variations. The first being the mutation of the SMCHD1 gene on chromosome 18p which in turn causes D4Z4 chromatin relaxation; and, the second variation being an FSHD-permissive haplotype on chromosome 4 such as 4qA161 allele needed for DUX4 expression. SMCHD1 mutations are not connected to the FSHD-permissive DUX4 alleles and they segregate independently. Complicating matters, about 20% of FSHD1B individuals with hypomethylation at D4Z4, a SMCHD1 mutation, and a permissive D4Z4 haplotype were asymptomatic, indicating an incomplete penetrance.

A FSHD1B diagnosis may also be caused by proximal and distal deletions that extend into D4Z4 that cause the standard genetic test to be “negative” even though the patient has the requisite number of deletions to cause FSHD. FSHD1B is also referred to as non-chromosome 4 linked FSHD. A common misconception is that FSHD1B is linked to the D4Z4 that is also present on the sub-telomere of chromosome 10. In fact, however, a shortened D4Z4 repeat on 10q26 does not cause FSHD or have anything to do with FSHD1B.

The online database Online Mendelian Inheritance in Man (OMIM) is an excellent source for further information on the science and medicine of FSHD 1B. OMIM was designed for use by physicians and other professionals concerned with genetic disorders, by genetics researchers, and by advanced students in science and medicine. OMIM is developed and maintained by the National Center for Biotechnology Information (NCBI). This database is a catalog of human genes and genetic disorders and has hyperlinks to MEDLINE and sequence records in the Entrez system, and links to additional related resources at NCBI and elsewhere.

To see the Online Mendelian Inheritance in Man pages on facioscapulohumeral muscular dystrophy 1B; FSHMD1B please click HERE.


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