title: [Clinical and molecular diagnosis of facioscapulohumeral dystrophy type 1 (FSHD1) in 2012].
abstract: BACKGROUND
  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.
  
  
  BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centre de référence des maladies neuromusculaires et de la SLA, hôpital La-Timone, avenue Jean-Moulin, 13005 Marseille, France; Inserm UMR_S 910 de génétique médicale et de génomique fonctionnelle, faculté de médecine secteur Timone, université Aix-Marseille, 27, boulevard Jean-Moulin, 13385 Marseille cedex 5, France. Electronic address: emmanuelle.salort-campana@ap-hm.fr.
authors.forename: E
authors.initials: E
authors.lastname: Salort-Campana
authors.forename: K
authors.initials: K
authors.lastname: Nguyen
authors.forename: N
authors.initials: N
authors.lastname: Lévy
authors.forename: J
authors.initials: J
authors.lastname: Pouget
authors.forename: S
authors.initials: S
authors.lastname: Attarian
mesh_terms: D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D025202:Molecular Diagnostic Techniques; D020391:Muscular Dystrophy, Facioscapulohumeral / Q000145:classification / Q000175:diagnosis* / Q000235:genetics; D019683:Penetrance; D010808:Physical Examination
keywords: Corrélation génotype–phénotype; Dystrophie facioscapulo-humérale; FSHD1; Facioscapulohumeral dystrophy; Genotype–phenotype correlation; Molecular combing; Peignage; Penetrance; Pénétrance