Work

Delineating the Clinical and Brain Imaging Characteristics of the Neonatal Form of CSTB ‐Related Neurodevelopmental Disorders

Year: 2025

Type: article

Abstract: Cystatin B gene (CSTB) is responsible for the most common childhood onset type of progressive myoclonic epilepsy (EPM1A). More recently, biallelic CSTB variants were described in four patients with a neonatal onset phenotype of microcephaly, diffuse hypomyelination, brain atrophic changes, and dyskinesia. Herein, we describe the clinical and molecular characterization of five additional patients in whom exome sequencing detected a splice variant (c.67-1G>C) in Family I and II and a missense variant (c.10G>C, p.Gly4Arg) in Family III and IV. Interestingly, these variants were described before in patients with EPM1A. However, all our patients had progressive microcephaly, developmental delay, and dyskinesia. In addition, only one patient developed seizures. Brain imaging showed mainly diffuse hypomyelination and progressive cerebral and cerebellar atrophy of variable severity. Interestingly, one patient showed intracranial calcification and another showed congenital distal arthrogryposis. Our findings support the association between CSTB variants and the neonatal form as a distinct neurodevelopmental phenotype. This newly characterized neonatal onset of the CSTB shares many overlapping features with genetic disorders encompassing microcephaly and hypomyelination.

Source: Clinical Genetics

DOI: 10.1111/cge.14720

Authors: Mohamed S. Abdel‐Hamid, Sherif F. Abdel‐Ghafar, Inas S. M. Sayed, Maha S. Zaki, Ghada M. H. Abdel‐Salam

Institution: National Research Centre

Language: English

Topic: Genetics and Neurodevelopmental Disorders

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

Funder: Science and Technology Development Fund