Phenotypic and Genetic Characterization of 64 Egyptian Children With Neuronal Ceroid Lipofuscinosis.

Abstract

BACKGROUND: Neuronal ceroid lipofuscinoses (NCLs) are the most common neurodegenerative diseases in childhood. This study aimed to investigate the phenotypic and genetic spectrum of NCLs in Egypt. METHODS: This descriptive study involved children with NCLs diagnosed and managed at five Egyptian centers between 2019 and 2024. Demographic, clinical, brain imaging, and genetic data were systematically evaluated. Identified variants in NCL-related genes were classified following the American College of Medical Genetics and Genomics guidelines. RESULTS: The cohort included 64 Egyptian children (from 57 families) with eight NCL types. The most commonly identified genotype was CLN2 (17/64, 27%), followed by CLN1 and CLN7 (12/64, 19% each). Patients generally exhibited the classic manifestations of NCLs, particularly motor regression (64/64, 100%), cognitive decline (64/64, 100%), language impairment (64/64, 100%), epilepsy (57/64, 89%), and vision loss (47/64, 73%). Notably, developmental regression (12/17, 71%) was the predominant presenting symptom for CLN2. Brain imaging generally showed typical cerebral and cerebellar atrophy in 95% (61/64) and 84% (54/64) of cases, respectively. Nevertheless, thalamic abnormalities were observed in only 16% (10/64) of cases. A total of 46 distinct variants were identified across eight NCL-related genes, including 23 novel ones, with the majority (33/46, 72%) being private. There was a median diagnostic delay of 2 years, and none of the patients received specific therapy. CONCLUSIONS: This study reports the largest cohort of children with NCLs from Egypt, including 12 patients with the less-commonly reported CLN7 subtype, which expands the demographic, clinical, and molecular spectrum of these diseases.