Atypical onset in a series of 122 cases with FacioScapuloHumeral Muscular Dystrophy

Abstract

IntroductionFacioScapuloHumeral Muscular Dystrophy (FSHD), a disease linked to a heterozygous D4Z4 deletion on chromosome 4q35, typically starts with shoulder-girdle and facial muscle involvement. Atypical presentations have occasionally been reported, but their frequency has still not been defined.Patients and methodsWe studied the occurrence rate of FSHD with atypical onset in 122 symptomatic subjects from 76 unrelated families with genetically confirmed FSHD. These 75 males and 47 females, with a mean age of 49 years (range: 11–85), had a mean EcoRI fragment of 25 kb (range: 11–38).ResultsTypical shoulder-girdle or facial weakness at onset was reported by 88 patients (72%). Unusual presentations included: foot drop in 16 (13%) and proximal lower limb weakness in eight patients (7%). Two cases at onset manifested quite atypical, apparently non-FSHD-related syndromes: a 42-year-old woman presented with infantile epilepsy and a 41-year-old man with myoglobinuria. In the latter patient, DNA analysis detected a 4q35 deletion associated to an heterozygous CAPN3 mutation.ConclusionFSHD presentation with foot drop or lower limb proximal weakness appeared to be more frequent than expected. This type of weakness at onset has to be considered premature, but still representative of disease-related muscle involvement. Quite atypical onset appears very rare and calls for further investigation on non-FSHD-related etiology.

Diagnostic evaluation of rhabdomyolysis

“…In a series of 122 cases of fascioscapulohumeral muscular dystrophy (FSHD), 1 patient was described with myoglobinuria 190 .…”

What's in a name? The clinical features of facioscapulohumeral muscular dystrophy

“…In one observational study (122 patients), 20% presented with lower limb weakness 14. The sequence of involvement of the leg muscles differs between patients.…”

SORBS2transcription is activated by telomere position effect–over long distance upon telomere shortening in muscle cells from patients with facioscapulohumeral dystrophy

“…FSHD symptoms appear during adolescence, with 95% of the individuals carrying the genetic defect affected by the age of 20 (Pastorello et al 2012;Deenen et al 2014). Although the underlying genetic alteration is present at birth, additional factors or epigenetic changes may trigger disease onset and participate in disease variability and penetrance.…”

“…FSHD is an autosomal dominant myopathy associated with a variable age of onset (Padberg et al 1995;Pastorello et al 2012). Clinical manifestations are heterogeneous; and in 90%-95% of FSHD cases, the disease onset is linked to contraction of multiple 3.3-kb tandem D4Z4 repeats located in the subtelomeric region of the long arm of Chromosome 4 (FSHD1A; 4q35 locus).…”