Microcephaly Associated with Abnormal Gyral Pattern

Abstract

Primary microcephaly is a heterogeneous group of cerebral malformations either with a relatively well-preserved or an abnormal gyral pattern. We describe the MRI findings and clinical features of 14 children with the combination of microcephaly and an abnormal gyral pattern. All children except one were Arabs and nine out of the 14 patients were born to consanguineous parents. Seven patients showed features of a simplified gyral pattern with relatively preserved posterior fossa structures. Two boys had a cortical malformation in the agyria-pachygyria spectrum; one of these two patients showed agenesis of the corpus callosum and severe cerebellar hypoplasia as well. The microcephaly was associated with polymicrogyria and leukoencephalopathy in two patients, with cortical dysplasia and hypogenesis of the corpus callosum in one patient, with agyria-pachygyria with callosal and pontocerebellar dysplasia in one patient, and a simplified gyral pattern with severe cerebellar hypoplasia in one case. One patient died in the neonatal period and three in infancy. All patients, who survived the neonatal period, had developmental delay, intellectual disability, and neurological deficits, and nine suffered from epilepsy.

Key words

Cerebral malformations - microcephaly - abnormal gyral pattern - cortical dysplasia

References

• 1 Abdulrazzaq Y M, Bener A, Al-Gazali L I, Al-Khayat A I, Micallef R, Gaber T. A study of possible deleterious effects of consanguinity.  Clin Genet. 1997;  51 167-173
• 2 Barkovich A J, Ferriero D M, Barr R M, Gressens P, Dobyns W B, Truwit C L. et al . Microlissencephaly: A heterogeneous malformation of cortical development.  Neuropediatrics. 1998;  29 113-119
• 3 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
• 4 Bittles A H. Consanguineous marriage and childhood health.  Dev Med Child Neurol. 2003;  45 571-576
• 5 Bond J, Roberts E, Mochida G H, Hampshire D J, Scott S, Askham J M. et al . ASPM is a major determinant of cerebral cortical size.  Nature Genet. 2002;  32 316-320
• 6 Bond J, Scott S, Hampshire J, Springell K, Corry P, Abramowicz M J. et al . Protein-truncating mutations in ASPM cause variable reduction in brain size.  Am J Hum Genet. 2003;  73 1170-1177
• 7 Chang B S, Piao X, Bodell A, Basel-Vanagaite L, Straussberg R, Dobyns W B. et al . Bilateral frontoparietal polymicrogyria: clinical and radiological features in 10 families with linkage to chromosome 16.  Ann Neurol. 2003;  53 596-606
• 8 Dobyns W B, Barkovich A J. Microcephaly with simplified gyral pattern (oligogyric microcephaly) and microlissencephaly: reply.  Neuropediatrics. 1999;  30 104-106
• 9 Jackson A P, Eastwood H, Bell S M, Adu J, Toomes C, Carr I M. et al . Identification of microcephalin, a protein implicated in determining the size of the human brain.  Am J Hum Genet. 2002;  71 136-142
• 10 Leal G F, Roberts E, Silva E O, Costa S MR, Hampshire D J, Woods C G. A novel locus for autosomal recessive primary microcephaly (MCPH6) maps to 13 q12. 2.  J Med Genet. 2003;  40 540-542
• 11 McCreary B D, Rossiter J P, Robertson D M. Recessive (true) microcephaly: a case report with neuropathological observations.  J Intellect Disabil Res. 1996;  40 66-70
• 12 Menkes J H, Sarnat H B. Malformations of the central nervous system; Part 2. Menkes JH, Sarnat HB Child Neurology. 6th ed. Philadelphia, Baltimore, New York, London, Buenos Aires, Hong Kong, Sydney, Tokyo; Lippincott Williams & Wilkin 2000: 305-400
• 13 Mochida G H, Walsh C A. Molecular genetics of human microcephaly.  Curr Opin Neurol. 2001;  14 151-156
• 14 Piao X, Hill R S, Bodell A, Chang B S, Basel-Vanagaite L, Straussberg R. et al . G protein-coupled receptor-dependent development of human frontal cortex.  Science. 2004;  303 2033-2036
• 15 Pilz D T, Matsumoto N, Minnerath S, Mills P, Gleeson J G, Allen K M. et al . LIS1 and XLIS (DCX) mutations cause most classical lissencephaly, but different patterns of malformation.  Hum Mol Genet. 1998;  7 2029-2037
• 16 Qazi Q H, Reed T E. A possible major contribution to mental retardation in the general population by the gene for microcephaly.  Clin Genet. 1975;  7 85-90
• 17 Roberts E, Hampshire D J, Pattison L, Springell K, Jafri H, Corry P. et al . Autosomal recessive primary microcephaly: an analysis of locus heterogeneity and phenotypic variation.  J Med Genet. 2002;  39 718-721
• 18 Sheen V L, Ganesh V S, Topcu M, Sebire G, Bodell A, Hill R S. et al . Mutations in ARFGEF2 implicate vesicle trafficking in neural progenitor proliferation and migration in the human cerebral cortex.  Nature Genet. 2004;  36 69-76
• 19 Sztriha L, Al-Gazali L I, Várady E, Goebel H H, Nork M. Autosomal recessive micrencephaly with simplified gyral pattern, abnormal myelination and arthrogryposis.  Neuropediatrics. 1999;  30 141-145
• 20 Sztriha L, Al-Gazali L, Várady E, Nork M, Varughese M. Microlissencephaly.  Pediatr Neurol. 1998;  18 362-365
• 21 Sztriha L, Guerrini R, Harding B, Stewart F, Chelloug N, Johansen J G. Clinical, MRI, and pathological features of polymicrogyria in chromosome 22 q11 deletion syndrome.  Am J Med Genet. 2004;  127 A 313-317
• 22 Sztriha L, Johansen J G, Al-Gazali L I. Extreme microcephaly with agyria-pachygyria, partial agenesis of the corpus callosum, and pontocerebellar dysplasia.  J Child Neurol. (accepted for publication); 
• 23 Sztriha L, Nork M. Bilateral frontoparietal polymicrogyria and epilepsy.  Pediatr Neurol. 2000;  22 240-243
• 24 Sztriha L, Nork M. Bilateral symmetrical frontoparietal polymicrogyria.  Eur J Paediatr Neurol. 2002;  6 229-232
• 25 Watemberg N, Silver S, Harel S, Lerman-Sagie T. Significance of microcephaly among children with developmental disabilities.  J Child Neurol. 2002;  17 117-122