Occipito-Temporal Polymicrogyria and Subclinical Muscular Dystrophy

Abstract

We report a two-year-old Caucasian boy who had neonatal seizures and was found to have bilateral occipito-temporal polymicrogyria on neonatal brain MRI. The child had no additional neurological abnormality other than the neonatal seizures, but serum CK was found to be elevated (5 - 7 times normal values) and the muscle biopsy showed evidence of early muscular dystrophy. Detailed protein and genetic studies did not allow the identification of a known form of muscular dystrophy. The boy has been followed regularly and he currently has mild global developmental delay but no clinical signs of muscle involvement. The association of polymicrogyria and muscular dystrophy is known to occur in Fukuyama and Walker Warburg muscular dystrophies, in muscle-eye-brain disease and in some patients with merosin deficient CMD. However the absence of weakness and of eye involvement, the normal expression of merosin and alpha dystroglycan and the pattern of brain involvement make it very unlikely that the child is affected by one of these forms. As the pattern of brain involvement and the muscle pathology is not typical of one of the forms of neuronal migration disorders secondary to a known gene defect, we suspect that the combination of muscle and brain involvement found in this child is not coincidental. Our findings suggest that serum CK should be determined in children with undiagnosed polymicrogyria, even in the absence of weakness. This may lead to an expansion of our understanding of muscle dystrophies and cortical dysplasias.

Muscular dystrophy - polymicrogyria - brain MRI

References

• 1 Barkovich A J, Kuzniecky R I, Jackson G D, Guerrini R, Dobyns W B. Classification system for malformations of cortical development: update 2001.  Neurology. 2001;  57 2168-2178
• 2 Couillard-Despres S, Winkler J, Uyanik G, Aigner L. Molecular mechanisms of neuronal migration disorders, quo vadis?.  Curr Mol Med. 2001;  1 677-688
• 3 Kitamura K, Yanazawa M, Sugiyama N. et al . Mutation of ARX causes abnormal development of forebrain and testes in mice and X-linked lissenecephaly with abnormal genitalia in humans.  Nature Genetics. 2002;  32 359-369
• 4 Mercuri E, Muntoni F. Congenital muscular dystrophies. Emery AEH The Muscular Dystrophies. Oxford; Oxford University Press 2001: 10-38
• 5 Moro F, Carrozo R, Veggiotti P, Tortorella G, Toniolo D, Volzone A, Guerrini R. Familial periventricular heterotropia: missense and distal truncating mutations of the FLN1 gene.  Neurology. 2002;  58 916-921
• 6 Muntoni F, Brockington M, Blake D, Torelli S, Brown S C. Defective glycosylation in muscular dystrophy.  Lancet. 2002;  360 1419-1421
• 7 Ruggieri V, Lubieniecki F, Diaz D, Ferragut E, Saito K, Fukuyama Y. et al . Merosin-positive congenital muscular dystrophy and central nervous system abnormalities unlinked to Fukuyama muscular dystrophy and muscular-eye-brain loci: report of three siblings.  Neuromuscul Disord. 2001;  11 570-578
• 8 Topaloglu H, Brockington M, Yuva Y, Talim B, Haliloglu G, Blake D, Torelli S, Brown S, Muntoni F. Mutations in the FKRP gene cause congenital muscular dystrophy 1 C, mental retardation and cerebellar cysts.  Neurology. 2003;  60 988-992
• 9 van der Flier A, Kuikman I, Kramer D, Geerts D, Kreft M, Takafuta T, Shapiro S S, Sonnenberg A. Different splice variants of filamin-B affect myogenesis, subcellular distribution, and determine binding to integrin [beta] subunits.  J Cell Biol. 2002;  156 361-376
• 10 Villanova M, Mercuri E, Bertini E, Sabatelli P, Morandi L, Mora M. et al . Congenital muscular dystrophy associated with calf hypertrophy, microcephaly and severe mental retardation: A new CMD syndrome.  Neuromusc Disord. 2000;  10 541-547
• 11 Mercuri E, Cowan F, Rutherford M, Acolet D, Pennock J, Dubowitz L. Haemorrhagic and ischaemic brain lesions in newborns with seizures and normal Apgar scores.  Arch Dis Child. 1995;  73 F67-74