Résumé :
|
Distal myopathies are rare muscular disorders clinically characterized by a predominantly distal muscular involvement. In France, among recessive forms, the myopathy resulting from mutations in the UDP-N-acetylglucosamine-2-epimerase/N-aetlymannosamine kinase (GNE) gene, often designated as Nonaka myopathy, occur in a minority of cases, far behind Miyoshi myopathy. However, the diagnosis is easily suspected on an weakness predominating on the anterior compartment of the leg and respecting the quadriceps muscle. In the Salpi, 7 patients with Nonaka myopathy have been genetically confirmed so far. Two of the patients are of Indian descent, two stem from North Africa, one from Senegal, and the 3 others were born in French Caucasian families. The mean age of onset in our patients was 24 years (range : 17-33 y). The first symptoms included pain in the calves in one patient and walking difficulties in all patients. The predominant involvement of the anterior compartment was conspicuous in all patients on examination, but in at least one patient, the first symptom noticed was a difficulty to get on tiptoes. The course of the disease is rather variable, ranging from mild forms with no gait loss after decades of progression of the disease to severe forms leading one patient to the wheelchair within 5 years; the quadriceps muscle was spared in all our cases. The distal upper limbs and axial muscles were involved in 4 cases. None of our patients showed any cardiac or respiratory involvement. CK levels were usually mildly elevated, with a mean level of 371 U/l (range : normal to 961 U/l. Muscle imaging plays a major part to confirm the predominant impairment of the anterior compartment of the leg and above all quadriceps sparing, which may be complete and contrast with severe fatty degeneration of the posterior muscles of the thigh. Electromyography is also of interest, but may be misleading: one of our patients was considered for years as having spinal CMT, as a consequence of equivocal neurogenic traces on the anterior compartments of the legs, a situation also found in other cases of distal myopathies. Muscle biopsy, avoiding the quadriceps and focusing on a distal muscle, can be of major help, showing rimmed vacuoles in 6 out of 7 of the patients in our series. The search for mutations yielded compound heterozygous mutations in 6 cases, and one homozygous mutation in the woman who displayed the most severe phenotype in our series. Interestingly, one patient required two genetic screenings before the mutation was confirmed.
|