Genotype-phenotype correlations in FSHD

BMC Med Genomics. 2019 Mar 13;12(Suppl 2):43. doi: 10.1186/s12920-019-0488-5.


Background: Facial-scapular-humeral myodystrophy Landouzy-Dejerine (FSHD) is an autosomal dominant disease, the basis of its pathogenesis is ectopic expression of the transcription factor DUX4 in skeletal muscle. There are two types of the disease: FSHD1 (MIM:158900) and FSHD2 (MIM: 158901), which have different genetic causes but are phenotypically indistinguishable. In FSHD1, partial deletion of the D4Z4 repeats on the 4th chromosome affects the expression of DUX4, whereas FSHD2 is caused by the mutations in the protein regulating the methylation status of chromatin - SMCHD1. High variability of clinical picture, both intra - and inter-family indicates a large number of factors influencing clinical picture. There are key genetic, epigenetic and gender factors that influence the expressivity and penetrance of the disease. Using only one of these factors allows just a rough prediction of the course of the disease, which indicates the combined effect of all of the factors on the DUX4 expression and on the clinical picture.

Results: In this paper, we analyzed the impact of genetic, epigenetic and gender differences on phenotype and the possibility of using them for disease prognosis and family counselling.

Conclusions: Key pathogenesis factors have been identified for FSHD. However, the pronounced intra - and inter-family polymorphism of manifestations indicates a large number of modifiers of the pathological process, many of which remain unknown.

Keywords: Anticipation; D4Z4; FSHD; Genotype-phenotype correlation; Inherited disease; Methylation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Chromosomes, Human, Pair 4
  • Epigenesis, Genetic
  • Genetic Association Studies*
  • Homeodomain Proteins / genetics
  • Humans
  • Muscular Dystrophy, Facioscapulohumeral / genetics
  • Muscular Dystrophy, Facioscapulohumeral / pathology*
  • Severity of Illness Index


  • DUX4L1 protein, human
  • Homeodomain Proteins