Abstract：
Pontocerebellar hypoplasia is a heterogeneous group of rare genetic neurodevelopmental disorders marked by early degeneration of the cerebellum and brainstem. Intellectual developmental disorder with microcephaly and pontine and cerebellar hypoplasia (MICPCH; MIM#300749) is a disorder caused by pathogenic loss-of-function variants in CASK CASK gene plays a critical role in brain development by controlling neuronal development and synapse formation. This report describes a 6-month-old Korean female infant with global developmental delay, sensorineural hearing loss, axial hypotonia with hypertonia of extremities, progressive microcephaly, and pontocerebellar hypoplasia. On whole exome sequencing, the patient had a novel heterozygous frameshift CASK variant, NM_003688.3:c.535del (NP_003679.2:p. Arg179Valfs*22). This report highlights the importance of considering CASK pathogenic variants in patients with global developmental delay, progressive microcephaly, and pontocerebellar hypoplasia and the genotype-phenotype relationships.
摘要：
前脑小脑发育不全是一组罕见的遗传性神经发育障碍，其特征是小脑和脑干的早期变性。具有小头畸形和脑桥和小脑发育不全的智力发育障碍（MICPCH;MIM#300749）是由CASK基因中的致病性功能丧失变体引起的疾病CASK通过控制神经元发育和突触形成在脑发育中起关键作用。本报告描述了一名6个月大的韩国女婴，患有全球发育迟缓，感觉神经性听力损失,轴向低张力伴四肢高张力，进行性小头畸形,桥小脑发育不全.在整个外显子组测序中，患者有一个新的杂合移码CASK变异体，NM_003688.3：c.535del（NP_003679.2：p。Arg179Valfs*22）。本报告强调了在全球发育迟缓患者中考虑CASK致病变异的重要性。进行性小头畸形,桥小脑发育不全和基因型-表型关系。
