Clinical and radiological features of Japanese patients with a severe phenotype due to CASK mutations
Clinical and radiological features of Japanese patients with a severe phenotype due to CASK mutations
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DOI：
10.1002/ajmg.a.35640
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发表时间：
2012-12-01
影响因子：
2
通讯作者：
Inazawa, Johji
中科院分区：
文献类型：
--
作者：
Takanashi, Jun-ichi;Okamoto, Nobuhiko;Inazawa, Johji
女性CASK基因Xp11.4杂合性功能缺失突变可导致严重智力残疾（ID）和伴有脑桥和小脑发育不全的小头畸形（MICPCH）。然而，受影响的患者的纵向临床和放射学过程，包括出生后的生长模式，还没有被描述。回顾性收集了16名日本（15名女性和1名男性）与CASK突变相关的ID和MICPCH患者的神经发育和影像学信息。对所有记录进行分析;最近一次检查时，患者年龄范围为2 - 16岁。15例女性患者的生长模式、神经系统发育、神经系统体征/症状和面部特征相似。他们出生时的头围约有一半在正常范围内，身高和体重通常也正常。其次是早期发展严重的小头畸形和出生后生长迟缓。患者在3至6个月内获得了几乎正常的头部控制，随后出现运动延迟。超过一半的女性患者患有癫痫。他们的核磁共振成像显示婴儿早期有小头畸形、脑干和小脑发育不全，胼胝体正常或较大。男性患者表现出更严重的临床表型。这些统一的临床和放射学特征应有助于早期诊断，并有助于与CASK突变相关的ID和MICPCH女性的医疗护理。(C)2012 Wiley Periodicals，Inc.
Heterozygous loss of function mutations of CASK at Xp11.4 in females cause severe intellectual disability (ID) and microcephaly with pontine and cerebellar hypoplasia (MICPCH). However, the longitudinal clinical and radiological course of affected patients, including patterns of postnatal growth, has not been described. Neurodevelopmental and imaging information was retrospectively accrued for 16 Japanese (15 female and 1 male) patients with ID and MICPCH associated with CASK mutations. All records were analyzed; patient age ranged from 2 to 16 years at the time of the most recent examinations. The growth pattern, neurological development, neurological signs/symptoms, and facial features were similar in the 15 female patients. Their head circumference at birth was within the normal range in about half, and their height and weight were frequently normal. This was followed by early development of severe microcephaly and postnatal growth retardation. The patients acquired head control almost normally between 3 and 6 months, followed by motor delay. More than half of the female patients had epilepsy. Their MRIs showed microcephaly, brainstem, and cerebellar hypoplasia in early infancy, and a normal or large appearing corpus callosum. The male patient showed a more severe clinical phenotype. These uniform clinical and radiological features should facilitate an early diagnosis and be useful for medical care of females with ID and MICPCH associated with CASK mutations. (C) 2012 Wiley Periodicals, Inc.