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

Marcello Villanova, Eugenio Mercuri, Enrico Bertini, Patrizia Sabatelli, Lucia Morandi, Marina Mora, Caroline Sewry, Martin Brockington, Susan C. Brown, Ana Ferreiro, Nadir M. Maraldi, Tatsushi Toda, Pascale Guicheney, Luciano Merlini, Francesco Muntoni

Research output: Contribution to journalArticle

Abstract

We describe four Italian patients (aged 3, 4, 12, and 13 years) affected by a novel autosomal form of recessive congenital muscular dystrophy. These patients were from three non-consanguineous families and presented an almost identical phenotype. This was characterized by hypotonia at birth, joint contractures 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 muscles. Ophthalmologic examination revealed no structural ocular abnormalities in any of the children; one patient had severe myopia. In all cases a magnetic resonance imaging of the brain showed an abnormal posterior cranial fossa with enlargement of the cisterna magna and variable hypoplasia of the vermis of the cerebellum. Abnormality of the white matter was also present in all patients, in the form of patchy signal most evident in the periventricular areas. Serum CK was grossly elevated in all. The muscle biopsy from all cases showed dystrophic changes compatible with congenital muscular dystrophy. Immunofluorescence studies showed mild to moderate partial deficiency of laminin α2 chain. Linkage analysis in the only informative family excluded the known loci for congenital muscular dystrophy, including laminin α2 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 dystrophy, with associated central nervous system involvement. (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)541-547
Number of pages7
JournalNeuromuscular Disorders
Volume10
Issue number8
DOIs
Publication statusPublished - 2000

Keywords

  • Congenital muscular dystrophy
  • Immunofluorescence
  • Italian families
  • Magnetic resonanace imaging

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health
  • Developmental Neuroscience
  • Neurology

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    Villanova, M., Mercuri, E., Bertini, E., Sabatelli, P., Morandi, L., Mora, M., Sewry, C., Brockington, M., Brown, S. C., Ferreiro, A., Maraldi, N. M., Toda, T., Guicheney, P., Merlini, L., & Muntoni, F. (2000). Congenital muscular dystrophy associated with calf hypertrophy, microcephaly and severe mental retardation in three Italian families: Evidence for a novel CMD syndrome. Neuromuscular Disorders, 10(8), 541-547. https://doi.org/10.1016/S0960-8966(00)00139-5