Résumé :
|
Fukuyama congenital muscular dystrophy (FCMD) is the second most common muscular dystrophy in Japan, usually due to a founder mutation of the fukutin gene. FCMD is characterized by severe congenital muscular dystrophy and mental retardation (MR). Out of Japan, fukutin mutations have been only reported in a few patients with Walker Warburg syndrome or a limb girdle muscular dystrophy (LGMD). We report four new Caucasian patients of three unrelated families. All showed high CK levels and dystrophic features in muscle. A 7 year-old French boy had calf hypertrophy, myalgia after effort and proximal motor weakness. Intelligence and brain MRI were normal. A Turkish 19 year-old girl, whose parents were consanguineous, required repeated ankle surgery at 3 and 7 years age and lost ambulation at 11 years. Intelligence and MRI were normal. Two Portuguese sisters presented congenital muscular dystrophy and MR. Facial weakness was observed in both. The older sister was able to walk a few steps until the age of 8 years and had a severe MR. Brain MRI showed cerebellar hypoplasia. She presented epileptic seizures at 13 years. Her younger sister never walked unaided, had muscle hypertrophy and developed a cardiomyopathy at the age of 15. She had mild MR. Brain MRI showed pontine hypoplasia and cerebellar malformation (vermis hypoplasia and polymicrogyria). Both sisters developed a respiratory insufficiency and required mechanical ventilation in the second decade. Skeletal muscle from the two LGMD patients showed markedly reduced glycosylation of ?-dystroglycan. Sequencing of fukutin gene identified three already described mutations (Y371C, R307Q, R47X) and two novel missense mutations (A170E, R246G). Fukutin mutations may be found in non-Japanese patients with muscular dystrophy and with or without MR. Epilepsy and cardiac involvement are particular findings. Among alpha-dystroglycanopathies, FCMD phenotype outside Japan has a clear overlap with that of FKRP mutated patients.
|