Compound heterozygosity in a South African patient with Facioscapulohumeral muscular dystrophy

Facioscapulohumeral muscular dystrophy (FSHD) is characterised by weakness and atrophy of the facial and shoulder girdle muscles. The FSHD phenotype segregates as an autosomal dominant trait and is caused by a deletion of an integral number of 3.3 kilobase pair (kb) repeat units on chromosome 4q35. Haplotype and Southern blot analyses of chromosome 4 resulted in the detection of two BlnI resistant deletion fragments, of 24 kb and 34 kb respectively, in a single individual from a South African FSHD family. The patient had moderate facial weakness and marked winging and high-riding of the scapulae with prominent pectoral and proximal arm muscle atrophy and weakness. Quadriceps and anterior tibial muscles were weak and the patient had bilateral foot drop. Although none of his children were symptomatic yet and only two showed very mild clinical signs, one had inherited the 24 kb deletion fragment, while the other two had the 34 kb deletion fragment. Molecular analysis conclusively identified the first compound heterozygous case in the South African FSHD population. However, in accordance with other studies of compound heterozygotes and clinical findings, no direct correlation between the clinical severity of this patient and the number of deletion fragments was observed.