Bonneau Dominique, Toutain Annick, Laquerrière Annie, Marret Stéphane, Saugier-Veber Pascale, Barthez Marie-Anne, Radi Sophie, Biran-Mucignat Valérie, Rodriguez Diana, Gélot Antoinette
Service de Génétique Médicale, Centre Hospitalier Universitaire d'Angers, Angers, France.
Ann Neurol. 2002 Mar;51(3):340-9. doi: 10.1002/ana.10119.
X-linked lissencephaly with absent corpus callosum and ambiguous genitalia is a newly recognized syndrome responsible for a severe neurological disorder of neonatal onset in boys. Based on the observations of 3 new cases, we confirm the phenotype in affected boys, describe additional MRI findings, report the neuropathological data, and show that carrier females may exhibit neurological and magnetic resonance imaging abnormalities. In affected boys, consistent clinical features of X-linked lissencephaly with absent corpus callosum and ambiguous genitalia are intractable epilepsy of neonatal onset, severe hypotonia, poor responsiveness, genital abnormalities, and early death. On magnetic resonance imaging, a gyration defect consisting of anterior pachygyria and posterior agyria with a moderately thickened brain cortex, dysplastic basal ganglia and complete agenesis of the corpus callosum are consistently found. Neuropathological examination of the brain shows a trilayered cortex containing exclusively pyramidal neurons, a neuronal migration defect, a disorganization of the basal ganglia, and gliotic and spongy white matter. Finally, females related to affected boys may have mental retardation and epilepsy, and they often display agenesis of the corpus callosum. These findings expand the phenotype of X-linked lissencephaly with absent corpus callosum and ambiguous genitalia, may help in the detection of carrier females in affected families, and give arguments for a semidominant X-linked mode of inheritance.
伴有胼胝体缺如和生殖器模糊的X连锁无脑回畸形是一种新发现的综合征，可导致男孩新生儿期严重的神经障碍。基于3例新病例的观察，我们证实了患病男孩的表型，描述了更多的MRI表现，报告了神经病理学数据，并表明携带者女性可能存在神经学和磁共振成像异常。在患病男孩中，伴有胼胝体缺如和生殖器模糊的X连锁无脑回畸形的一致临床特征为新生儿期难治性癫痫、严重肌张力低下、反应性差、生殖器异常和早期死亡。在磁共振成像上，始终发现由前部巨脑回和后部无脑回组成的脑回形成缺陷，脑皮质中度增厚，基底神经节发育异常以及胼胝体完全缺如。对大脑的神经病理学检查显示，皮质为仅含锥体细胞的三层结构，存在神经元迁移缺陷、基底神经节结构紊乱以及胶质化和海绵状白质。最后，与患病男孩相关的女性可能有智力障碍和癫痫，且她们常表现为胼胝体缺如。这些发现扩展了伴有胼胝体缺如和生殖器模糊的X连锁无脑回畸形的表型，可能有助于在患病家庭中检测携带者女性，并为X连锁半显性遗传模式提供依据。
