Congenital muscular dystrophy associated with calf hypertrophy, microcephaly and severe mental retardation in three Italian families: evidence for a novel CMD syndrome

We describe four Italian patients (aged 3, 4, 12, and 13 years) affected by a novel autosomal form of recessive congenital muscular dystrophy. These p atients were from three non-consanguineous families and presented an almost identical phenotype. This was characterized by hypotonia at birth, joint c ontractures associated with severe psychomotor retardation, absent speech, inability to walk and almost no interest in their surroundings. In addition , all patients had a striking enlargement of the calf and quadriceps muscle s. Ophthalmologic examination revealed no structural ocular abnormalities i n any of the children; one patient had severe myopia. In all cases a magnet ic resonance imaging of the brain showed an abnormal posterior cranial foss a with enlargement of the cisterna magna and variable hypoplasia of the ver mis of the cerebellum. Abnormality of the white matter was also present in all patients, in the form of patchy signal most evident in the periventricu lar areas. Serum CK was grossly elevated in all. The muscle biopsy from all cases showed dystrophic changes compatible with congenital muscular dystro phy. Immunofluorescence studies showed mild to moderate partial deficiency of laminin alpha2 chain. Linkage analysis in the only informative family ex cluded the known loci for congenital muscular dystrophy, including laminin alpha2 chain on chromosome 6q2, the Fukuyama congenital muscular dystrophy locus on 9q3 and the muscle-eye-brain disease on chromosome 1p3. We propose that this represent a novel severe variant of congenital muscular dystroph y, with associated central nervous system involvement. (C) 2000 Elsevier Sc ience B.V. All rights reserved.