Limb-girdle muscular dystrophy with apparently different clinical courses within sexes in a large inbred kindred

Editor—The autosomal recessive limb-girdle muscular dystrophies (AR-LGMD) are clinical entities characterised by primary and progressive muscle degeneration, mainly at the pelvic and shoulder girdles, with great variability in the clinical course. Some patients present a severe course similar to Duchenne muscular dystrophy, while others maintain the capacity to walk even in adult life.1-3 At least eight autosomal recessive genes have been mapped. The chromosome localisation of these genes and their products, and a brief comment on the clinical course of each type of AR-LGMD are summarised in table 1. Of these mapped genes, six have been cloned: the gene responsible for LGMD2A which encodes calpain 3, a muscle specific protease,30 the genes that cause the known sarcoglycanopathies (LGMD2C-LGMD2F),11 15 20 22 26and, recently, the gene for LGMD2B which encodes a protein called “dysferlin” by the investigators.8

LGMD2C is a Duchenne-like muscular dystrophy particularly prevalent in North Africa,10-12 31 32 but rare in other geographical regions; its prevalence in north eastern Italy was estimated to be 1.72 × 10^-6 inhabitants.33 This phenotype, which affects both sexes equally, was first described by Ben Hamidaet al 12 in 93 patients belonging to 28 Tunisian families. A few large kindreds, with many affected persons, have been described. Here we report the results of a clinical and molecular study in a large inbred kindred from the north east of Brazil with LGMD2C, which is unusual because the male patients appear to have a more severe clinical course than the affected females.

The genealogical data from five generations (fig 1) were obtained and confirmed by different family members. The dates of birth, marriage, and death, causes of death, and abortions were documented. A total of 56 subjects, including …