A novel form of familial congenital muscular dystrophy in two adolescents

We report on two brothers (the product of first-degree consanguineous marri age; aged 15 and 12 years) who presented with severe hypotonia at birth, pr oximal muscle weakness associated with delayed motor milestones but normal cognitive function. Investigations (at 4 years of age) revealed mildly elev ated serum creatine kinase (CK) levels (300 and 824 IU/I; N less than or eq ual to 210). Muscle biopsies showed minimal change myopathy, no neurogenic atrophy but remarkable type-1 fibre predominance (up to 85.5 %) without fib re-type disproportion. Clinical examination at 12 and 9 years, respectively, showed mild facial we akness and high-arched palate in both patients. The younger sibling also ha d ptosis but otherwise normal external ocular muscles. They showed symmetri c proximal muscle weakness and wasting associated with calf-muscle hypertro phy. They could walk independently. A repeat muscle biopsy showed advanced dystrophic changes in the younger patient at the age of 10 years. Virtually all the remaining fibres were type 1. Immunohistochemistry revealed normal expression of the dystrophin-glycoprot ein complex (DGC), including dystrophin, beta-dystroglycan, alpha-(adhalin) , beta-, gamma-, and delta-sarcoglycan, laminin-alpha 2 chain (merosin) and syntrophin. Mild dystrophic features and type-1 fibre predominance (92.5 % ) were seen in the biopsy of the older patient, whereas immunohistochemistr y showed normal expression of the DGC. Both cases also showed clear express ion of integrin alpha 7 at the muscle fibre surface and in the blood vessel s. Three years later, they could still walk, but with difficulty, and the o lder brother showed enlargement of the tongue and echocardiographic feature s of left ventricular dilated cardiomyopathy.