BACKGROUND MICPCH is manifested as microcephaly associated with pontocerebellar hypoplasia and global developmental delay but developmental regression has never been reported. We describe the detailed clinical history of a woman with intellectual disability and microcephaly with pontine and cerebellar hypoplasia (MICPCH) with a CASK mutation who exhibited gross motor regression after adolescence. CASE The patient experienced severe motor and intellectual developmental delay with microcephaly from infancy. The initial diagnosis was Rett syndrome based on her clinical features, including hand stereotypes and the absence of structural abnormality on magnetic resonance imaging (MRI) performed at the age of 5 years. Although gross motor abilities developed slowly and she could walk independently, she never acquired speech or understanding of languages. After adolescence, her motor ability gradually regressed so that she was unable to stand without support and moved with a wheelchair. At the age of 31 years, because of her atypical clinical course for Rett syndrome, whole exome sequencing was performed, which revealed a de novo heterozygous c.2068 + 1G > A mutation in the CASK gene (NM_001126055). Brain MRI revealed mild pontocerebellar hypoplasia compatible with the clinical phenotype of MICPCH. DISCUSSION This case suggests that MICPCH with a CASK mutation might cause developmental regression after adolescence and might be regarded as a neurodegenerative disorder.

中文翻译：

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具有 CASK 突变的 MICPCH 的最老病例表现出粗大运动退化

背景MICPCH表现为与脑桥小脑发育不全和整体发育迟缓相关的小头畸形，但从未报道过发育倒退。我们描述了一名患有脑桥和小脑发育不全 (MICPCH) 并伴有 CASK 突变的智力障碍和小头畸形女性的详细临床病史，她们在青春期后表现出粗大运动退化。案例 该患者从婴儿时期就经历了严重的运动和智力发育迟缓，并伴有小头畸形。根据她的临床特征，包括手的刻板印象和 5 岁时进行的磁共振成像 (MRI) 中没有结构异常，初步诊断为雷特综合征。虽然粗大运动能力发展缓慢，她可以独立行走，但她从未学会说话或理解语言。青春期后，她的运动能力逐渐退化，以至于她无法独立站立，只能靠轮椅移动。31岁时，由于她的非典型Rett综合征临床病程，进行了全外显子组测序，结果显示CASK基因（NM_001126055）中有一个de novo杂合c.2068 + 1G > A突变。脑部 MRI 显示轻度脑桥小脑发育不全，符合 MICPCH 的临床表型。讨论 本病例表明，带有 CASK 突变的 MICPCH 可能会导致青春期后的发育倒退，并可能被视为一种神经退行性疾病。进行了全外显子组测序，结果显示 CASK 基因 (NM_001126055) 中存在一个 de novo 杂合 c.2068 + 1G > A 突变。脑部 MRI 显示轻度脑桥小脑发育不全，符合 MICPCH 的临床表型。讨论 本病例表明，带有 CASK 突变的 MICPCH 可能会导致青春期后的发育倒退，并可能被视为一种神经退行性疾病。进行了全外显子组测序，结果显示 CASK 基因 (NM_001126055) 中存在一个 de novo 杂合 c.2068 + 1G > A 突变。脑部 MRI 显示轻度脑桥小脑发育不全，符合 MICPCH 的临床表型。讨论 本病例表明，带有 CASK 突变的 MICPCH 可能会导致青春期后的发育倒退，并可能被视为一种神经退行性疾病。