A de novo variant in CASK gene causing intellectual disability and brain hypoplasia: a case report and literature review

• Published in: Italian journal of pediatrics 2022-05, Vol.48 (1), p.73-73, Article 73
• Main Authors: Zhang, Ying, Nie, Yanyan, Mu, Yu, Zheng, Jie, Xu, Xiaowei, Zhang, Fang, Shu, Jianbo, Liu, Yang
• Format: Article
• Language: English
• Subjects: Amino acids; Bioinformatics; Brain - diagnostic imaging; Brain dysplasia; Case Report; CASK gene; Cerebellum; Children & youth; Diagnosis; Disease; Families & family life; Gene expression; Gene variant; Genetic screening; Growth rate; Guanylate Kinases - chemistry; Guanylate Kinases - genetics; Humans; Hypoplasia; Intellectual disabilities; Intellectual disability; Intellectual Disability - diagnosis; Intellectual Disability - genetics; Kinases; Literature reviews; Male; Mental disorders; Mental Retardation, X-Linked - complications; Mental Retardation, X-Linked - diagnosis; Mental Retardation, X-Linked - genetics; Microcephaly; Microcephaly - complications; Microcephaly - diagnosis; Microcephaly - genetics; Microencephaly; Mutation; Nystagmus; Phenotypes; Proteins; Signal transduction
• ISSN: 1824-7288; 1720-8424; 1824-7288
• DOI: 10.1186/s13052-022-01248-z

The pathogenic variation of CASK gene can cause CASK related mental disorders. The main clinical manifestations are microcephaly with pontine and cerebellar hypoplasia, X-linked mental disorders with or without nystagmus and FG syndrome. The main pathogenic mechanism is the loss of function of related protein caused by variant. We reported a Chinese male newborn with a de novo variant in CASK gene. We present an 18-day-old baby with growth retardation and brain hypoplasia. Whole-exome sequencing was performed, which detected a hemizygous missense variant c.764G > A of CASK gene. The variant changed the 255th amino acid from Arg to His. Software based bioinformatics analyses were conducted to infer its functional effect. In this paper, a de novo variant of CASK gene was reported. Moreover, a detailed description of all the cases described in the literature is reported. CASK variants cause a variety of clinical phenotypes. Its diagnosis is difficult due to the lack of typical clinical symptoms. Genetic testing should be performed as early as possible if this disease is suspected. This case provides an important reference for the diagnosis and treatment of future cases.