Article

Diagnosis of facioscapulohumeral dystrophy type 1 (FSHD1) is
supported by a suggestive clinical presentation and associated with a
heterozygous contraction of the D4Z4 repeat array on chromosome 4q35. STATE OF THE ART : The FSHD1 phenotype has a widely variable course with great inter- and
intrafamilial heterogeneity. Three clinical forms can be distinguished: the
classical phenotype associated with four to seven repeat units (RU) and a
variable course, a severe infantile form with one to three RU, and a mild
phenotype associated with borderline UR (8 to 10 RU). At the molecular level, for
D4Z4 contraction to be pathogenic, it needs to occur on a specific chromosomal
background, namely on the 4qA allelic variant of chromosome 4. In most cases,
once FSHD is clinically suspected, the diagnosis can be genetically confirmed
with a DNA test using Southern Blotting and hybridization to a set of probes.
However, diagnosis of FSHD1 remains challenging. Firstly, some patients may
present with an atypical phenotype with highly focal or unusual symptoms.
Secondly, there are potential pitfalls in the genetic diagnosis of FSHD resulting
in false positive or false negative results. In the absence of genetic
confirmation, other investigations, mainly EMG and muscle biopsy, are needed to
rule out another diagnosis. In cases with no clear diagnosis and a permissive
chromosome without contraction, FSHD2 may be suspected. PERSPECTIVES: Molecular
combing is a new technique which permits visualization and sizing of the D4Z4
repeat array on its genetic background on stretched single DNA fibers by
fluorescence microscopy. This tool will improve genetic diagnosis in FSHD
patients. CONCLUSION: Diagnosis of FSHD1 is mainly supported by clinical
features. Clinicians need to be aware of unusual presentations of this disease.
The wide spectrum of intrafamilial variability and the lack of good correlation
between genotype and phenotype present challenges for genetic counseling and
prognostication. More studies are needed concerning penetrance and
genotype-phenotype correlation.
CI - Copyright (c) 2013 Elsevier Masson SAS. All rights reserved.

Langue : FRANCAIS