Mega-Corpus Callosum, Polymicrogyria, and Psychomotor Retardation: Confirmation of a Syndromic Entity

Abstract

A mega-corpus callosum (CC) is not a common manifestation of neurological disease. Previous reports of patients with a constellation of findings including megalencephaly, perisylvian polymicrogyria, distinct facies, psychomotor retardation and mega-corpus callosum were designated as having megalencephaly, mega-corpus callosum, and complete lack of motor development [OMIM 603387; also referred to as megalencephaly-polymicrogyria-mega-corpus callosum (MEG-PMG-MegaCC)] syndrome. Three patients were initially reported with this syndrome, and a fourth was reported recently. Another case had similar findings in utero and upon autopsy. We present an additional patient who conforms to this phenotype; however, he is not megalencephalic, but has a normal head circumference in the setting of short stature. This patient is also noted to have abnormal saccades and mask-like facies. His motor function is more developed than in the other reported patients and was further improved by treatment with l-DOPA/carbidopa, which was started because of his extrapryramidal symptoms and signs which were associated with low cerebral spinal fluid (CSF) catecholamine levels.

mega-corpus callosum - megalencephaly - delayed motor function - MEG-PMG-MegaCC

References

• 1 Assmann BE, Robinson RO, Surtees RA. et al . Infantile Parkinsonism-dystonia and elevated dopamine metabolites in CSF.  Neurology. 2004;  62 1872-1874
• 2 Barkovich AJ, Kjos BO. Normal postnatal development of the corpus callosum as demonstrated by MR imaging.  AJNR Am J Neuroradiol. 1988;  9 487-491
• 3 Barkovich AJ, Kjos BO, Jackson  Jr  DE, Norman D. Normal maturation of the neonatal and infant brain: MR imaging at 15.T.  Radiology. 1988;  166 173-180
• 4 Barkovich AJ, Maroldo TV. Magnetic resonance imaging of normal and abnormal brain development.  Top Magn Reson Imaging. 1993;  5 96-122
• 5 Cavicchioni O, Gomes DM, Leroy B. et al . Prenatal diagnosis of de novo (7;19)(q11.2;q13.3) translocation associated with a thick corpus callosum and Wilms tumor of the kidneys.  Prenat Diagn. 2005;  25 876-878
• 6 Dagli AI, Stalker HJ, Williams CA. A patient with the syndrome of megalencephaly, mega-corpus callosum and complete lack of motor development.  Am J Med Genet A. 2008;  146 204-207
• 7 DiMario  Jr  FJ, Ramsby GR, Burleson JA. Brain morphometric analysis in neurofibromatosis 1.  Arch Neurol. 1999;  56 1343-1346
• 8 Dubovsky EC, Booth TN, Vezina G. et al . MR imaging of the corpus callosum in pediatric patients with neurofibromatosis type 1.  AJNR Am J Neuroradiol. 2001;  22 190-195
• 9 Giedd JN, Blumenthal J, Jeffries NO. et al . Development of the human corpus callosum during childhood and adolescence: a longitudinal MRI study.  Prog Neuropsychopharmacol Biol Psychiatry. 1999;  23 571-588
• 10 Gohlich-Ratmann G, Baethmann M, Lorenz P. et al . Megalencephaly, mega-corpus callosum, and complete lack of motor development: a previously undescribed syndrome.  Am J Med Genet. 1998;  79 161-167
• 11 Hyland K, Surtees RA, Heales SJ. et al . Cerebrospinal fluid concentrations of pterins and metabolites of serotonin and dopamine in a pediatric reference population.  Pediatr Res. 1993;  34 10-14
• 12 Kier EL, Truwit CL. The normal and abnormal genu of the corpus callosum: an evolutionary, embryologic, anatomic, and MR analysis.  AJNR Am J Neuroradiol. 1996;  17 1631-1641
• 13 Kivitie-Kallio S, Autti T, Salonen O, Norio R. MRI of the brain in the Cohen syndrome: a relatively large corpus callosum in patients with mental retardation and microcephaly.  Neuropediatrics. 1998;  29 298-301
• 14 Kivitie-Kallio S, Norio R. Cohen syndrome: essential features, natural history, and heterogeneity.  Am J Med Genet. 2001;  102 125-135
• 15 Kolehmainen J, Black GC, Saarinen A. et al . Cohen syndrome is caused by mutations in a novel gene, COH1, encoding a transmembrane protein with a presumed role in vesicle-mediated sorting and intracellular protein transport.  Am J Hum Genet. 2003;  72 1359-1369
• 16 Malinow MR, Nieto FJ, Kruger WD. et al . The effects of folic acid supplementation on plasma total homocysteine are modulated by multivitamin use and methylenetetrahydrofolate reductase genotypes.  Arterioscler Thromb Vasc Biol. 1997;  17 1157-1162
• 17 Mirzaa G, Dodge NN, Glass I. et al . Megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus: a rare brain malformation syndrome associated with mental retardation and seizures.  Neuropediatrics. 2004;  35 353-359
• 18 Northrup H, Volcik KA. Spina bifida and other neural tube defects.  Curr Probl Pediatr. 2000;  30 313-332
• 19 Poyhonen MH, Peippo MM, Valanne LK. et al . Hypertrichosis, hyperkeratosis, abnormal corpus callosum, mental retardation and dysmorphic features in three unrelated females.  Clin Dysmorphol. 2004;  13 85-90
• 20 Rakic P, Yakovlev PI. Development of the corpus callosum and cavum septi in man.  J Comp Neurol. 1968;  132 45-72
• 21 Rosenbaum T, Kim HA, Boissy YL, Ling B, Ratner N. Neurofibromin, the neurofibromatosis type 1 Ras-GAP, is required for appropriate P0 expression and myelination.  Ann N Y Acad Sci. 1999;  883 203-214
• 22 Rypens F, Sonigo P, Aubry MC. et al . Prenatal MR diagnosis of a thick corpus callosum.  AJNR Am J Neuroradiol. 1996;  17 1918-1920
• 23 Put NM van der, Gabreels F, Stevens EM. et al . A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects?.  Am J Hum Genet. 1998;  62 1044-1051
• 24 Ward BA, Gutmann DH. Neurofibromatosis 1: from lab bench to clinic.  Pediatr Neurol. 2005;  32 221-228
• 25 Yamanouchi H, Kato T, Matsuda H. et al . MRI in neurofibromatosis type I: using fluid-attenuated inversion recovery pulse sequences.  Pediatr Neurol. 1995;  12 286-290

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