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facioscapulohumeral muscular dystrophy

Wednesday 13 October 2004

Autosomal dominant facioscapulohumeral muscular dystrophy (FSHD) is mainly characterized by progressive wasting and weakness of the facial, shoulder, and upper-arm muscles.

FSHD is caused by contraction of the macrosatellite repeat D4Z4 on chromosome 4q35.

The D4Z4 repeat is very polymorphic in length, and D4Z4 rearrangements occur almost exclusively via intrachromosomal gene conversions.

Several disease mechanisms have been proposed, but none of these models can comprehensively explain FSHD, because repeat contraction alone is not sufficient to cause disease.

Almost-identical D4Z4-repeat arrays have been identified on chromosome 10q26 and on two equally common chromosome 4 variants, 4qA and 4qB.

Yet only repeat contractions of D4Z4 on chromosome 4qA cause FSHD; contractions on the other chromosomes are nonpathogenic.

Repeat contractions in two of the nine haplotypes, one of which is a 4qA haplotype, are not associated with FSHD. Each of these haplotypes has its unique sequence signature.


- FSHD is associated with contractions of the D4Z4 repeat in the subtelomere of chromosome 4q (15467981, 15674778)
- Specific sequence variations within the 4q35 region (17924332)


- Clapp J, Mitchell LM, Bolland DJ, Fantes J, Corcoran AE, Scotting PJ, Armour JA, Hewitt JE. Evolutionary conservation of a coding function for D4Z4, the tandem DNA repeat mutated in facioscapulohumeral muscular dystrophy. Am J Hum Genet. 2007 Aug;81(2):264-79. PMID: 17668377

- Lemmers RJ, Wohlgemuth M, van der Gaag KJ, van der Vliet PJ, van Teijlingen CM, de Knijff P, Padberg GW, Frants RR, van der Maarel SM. Specific Sequence Variations within the 4q35 Region Are Associated with Facioscapulohumeral Muscular Dystrophy. Am J Hum Genet. 2007 Nov;81(5):884-94. PMID: 17924332