Division of Human Genetics and Genome Research, Department of Clinical Genetics, National Research Centre, Cairo, Egypt.
Am J Med Genet A. 2012 Aug;158A(8):1823-31. doi: 10.1002/ajmg.a.35480. Epub 2012 Jul 11.
We describe two sibs with a lethal form of profound congenital microcephaly, intrauterine and postnatal growth retardation, subtle skeletal changes, and poorly developed brain. The sibs had striking absent cranial vault with sloping of the forehead, large beaked nose, relatively large ears, and mandibular micro-retrognathia. Brain magnetic resonance imaging (MRI) revealed extremely simplified gyral pattern, large interhemispheric cyst and agenesis of corpus callosum, abnormally shaped hippocampus, and proportionately affected cerebellum and brainstem. In addition, fundus examination showed foveal hypoplasia with optic nerve atrophy. No abnormalities of the internal organs were found. This profound form of microcephaly was identified at 17 weeks gestation by ultrasound and fetal brain MRI helped in characterizing the developmental brain malformations in the second sib. Molecular analysis excluded mutations in potentially related genes such as RNU4ATAC, SLC25A19, and ASPM. These clinical and imaging findings are unlike that of any recognized severe forms of microcephaly which is believed to be a new microcephalic primordial dwarfism (MPD) with developmental brain malformations with most probably autosomal recessive inheritance based on consanguinity and similarly affected male and female sibs.
我们描述了两例具有致命形式的严重先天性小头畸形的同胞，其表现为宫内和产后生长迟缓、细微的骨骼变化以及大脑发育不良。这些同胞具有显著的颅穹窿缺失，表现为额头倾斜、大钩鼻、相对较大的耳朵和下颌后缩。脑部磁共振成像（MRI）显示出非常简化的脑回模式、大脑半球间大囊肿和胼胝体发育不全、海马形状异常以及小脑和脑干不成比例地受累。此外，眼底检查显示黄斑发育不良伴视神经萎缩。未发现内脏器官异常。这种严重的小头畸形在 17 周妊娠时通过超声检查发现，胎儿脑部 MRI 有助于在第二例同胞中描述发育性脑畸形。分子分析排除了 RNU4ATAC、SLC25A19 和 ASPM 等潜在相关基因的突变。这些临床表现和影像学特征与任何已识别的严重小头畸形均不相同，这可能是一种新的小头原始侏儒症（MPD），具有发育性脑畸形，最有可能基于近亲婚配和同样受影响的男性和女性同胞的常染色体隐性遗传。
