Ataxia and Congenital Muscular Dystrophy: the follow-up of a new specific phenotype

Cerebellar hypoplasia may, at neuroimaging studies, be found in association with congenital muscular dystrophy (CMD). although it is an extremely rare occurrence. We here report on three CMD patients who underwent a longitudi nal evaluation of clinical and neuroimaging features for a mean period of I S years. Case 1, a 22-year-old woman, and cases 2 and 3, brothers aged 70 a nd 20 years, respectively, had presented a mild to moderate muscular weakne ss and increased serum creatine kinase (CK levels since birth. All cases we re diagnosed in the first years of life, with identification of evident dys trophic changes at muscle biopsy and moderate to severe cerebellar hypoplas ia at brain computed tomography (CT) scan. Subsequently all the patients un derwent a second muscle biopsy, with immunostaining and immunoblot analysis , which showed normal values for merosin, dystrophin and dystrophin-related proteins. During the longitudinal study, the patients underwent repeated n eurological and psychiatric examinations, serum CK controls, intellectual a bility assessments and neuroimaging evaluations (CT and/or magnetic resonan ce imaging (MRI)). In all cases, these investigations indicated a mild to m oderate deficit in the proximal muscles and a clear-cut cerebellar syndrome which, it was assumed, had been present since the first years. The patient s also presented some intellectual difficulties, with an IQ of 0.69 in case 1, 0.83 in case 2 and 0.61 in case 3. The clinical course of all the patie nts was static, and all symptoms of the combined muscle and brain involveme nt persisted. Nor were any changes in the cerebellar hypoplasia observed at repeat MRIs. Findings obtained by us on the longitudinal study and a revie w of the literature indicate that cerebellar hypoplasia and merosin-positiv e CMD constitute a particular clinical phenotype, mainly characterized by a n ataxic syndrome associated with a nonsevere muscular involvement and a po ssible mild intellectual impairment. (C) 1001 Elsevier Science B.V. All rig hts reserved.