Abdel-Salam Ghada M H, Abdel-Hamid Mohamed S, El-Khayat Hamed A, Eid Ola M, Saba Soliman, Farag Mona K, Saleem Sahar N, Gaber Khaled R
Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
Am J Med Genet A. 2015 May;167A(5):1089-99. doi: 10.1002/ajmg.a.37010. Epub 2015 Mar 10.
The term fetal brain disruption sequence (FBDS) was coined to describe a number of sporadic conditions caused by numerous external disruptive events presenting with variable imaging findings. However, rare familial occurrences have been reported. We describe five patients (two sib pairs and one sporadic) with congenital severe microcephaly, seizures, and profound intellectual disability. Brain magnetic resonance imaging (MRI) revealed unique and uniform picture of underdeveloped cerebral hemispheres with increased extraxial CSF, abnormal gyral pattern (polymicrogyria-like lesions in two sibs and lissencephaly in the others), loss of white matter, dysplastic ventricles, hypogenesis of corpus callosum, and hypoplasia of the brainstem, but hypoplastic cerebellum in one. Fetal magnetic resonance imaging (FMRI) of two patients showed the same developmental brain malformations in utero. These imaging findings are in accordance with arrested brain development rather than disruption. Molecular analysis excluded mutations in potentially related genes such as NDE1, MKL2, OCLN, and JAM3. These unique clinical and imaging findings were described before among familial reports with FBDS. However, our patients represent a recognizable phenotype of developmental brain malformations, that is, apparently distinguishable from either familial microhydranencephaly or microlissencephaly that were collectively termed FBDS. Thus, the use of the umbrella term FBDS is no longer helpful. Accordingly, we propose the term fetal brain arrest to distinguish them from other familial patients diagnosed as FBDS. The presence of five affected patients from three unrelated consanguineous families suggests an autosomal-recessive mode of inheritance. The spectrum of fetal brain disruption sequence is reviewed.
术语“胎儿脑发育中断序列征（FBDS）”用于描述由多种外部干扰事件引起的一系列散发性疾病，这些疾病具有多样的影像学表现。然而，也有罕见的家族性发病报道。我们描述了5例患者（两对同胞和1例散发病例），他们患有先天性严重小头畸形、癫痫和严重智力残疾。脑磁共振成像（MRI）显示出独特且一致的图像，即大脑半球发育不全，脑外脑脊液增多，脑回模式异常（两例同胞为多小脑回样病变，其他为无脑回畸形），白质丢失，脑室发育异常，胼胝体发育不全，脑干发育不全，但其中1例小脑发育不全。两名患者的胎儿磁共振成像（FMRI）显示子宫内存在相同的脑发育畸形。这些影像学表现符合脑发育停滞而非发育中断。分子分析排除了潜在相关基因如NDE1、MKL2、OCLN和JAM3中的突变。这些独特的临床和影像学表现在之前的FBDS家族报告中已有描述。然而，我们的患者代表了一种可识别的脑发育畸形表型，明显有别于统称为FBDS的家族性脑穿通畸形或微小无脑回畸形。因此，使用笼统的术语FBDS已不再有用。相应地，我们提出“胎儿脑停滞”这一术语，以将他们与其他诊断为FBDS的家族性患者区分开来。来自三个无亲缘关系的近亲家庭的5例受累患者提示为常染色体隐性遗传模式。本文对胎儿脑发育中断序列征的范围进行了综述。
