Limb-Girdle Muscular Dystrophy (LGMD): Diagnosis in An Arab Country

Abstract

Limb-girdle Muscular Dystrophies (LGMD) are heterogeneous inherited muscle disorders characterized by progressive weakness and muscle wasting. They show a wide spectrum of clinical courses, varying from very mild to severe. It is a genetically heterogeneous group of diseases with dominant (LGMD1) and recessive (LGMD2) inheritance. To date, at least 31 loci have been identified. The different subtypes can be distinguished by immunohistochemical analysis in a muscle biopsy specimen in order to guide and abbreviate the molecular genetic investigations. There is a geographical difference in their incidence. LGMD2 are prevalent in Arabic countries because of the high rates of consanguinity. Many genes were identified in these countries, especially in Maghreb. LGMD type 2C, or δ- sarcoglycanopathy, is the most frequent in North African populations as a result of the founder c.525delT mutation in the Sarcoglycan gene. It was firstly described in Tunisia, in 1977, by Ben Hmida in a large consanguineous Tunisian family with Duchenne like phenotype affecting both girls and boys. It is characterized by a childhood onset of progressive muscular dystrophy. The mean age of onset is between 5 and 6 years, and half of these patients lose ambulation by age 12 years. Calf hypertrophy and lumbar lordosis are common. Diagnosis confirmation is based on muscle biopsy and molecular study. The scarcities of specialized centers and difficulties that can prevent patients from benefitting from immunohistochemical analysis complicate their diagnosis, management, and genetic counseling. We therefore propose, in our context, that screening for c.525delT could be the first test for AR-LGMD, with a good cost/benefit ratio in public health strategies, until access to immunohistochemical analysis will be generalized. This might be useful not only for management of patients, genetic counseling, and prenatal diagnosis in families but also for novel therapeutic approaches and future clinical trials.