Individuals with CLCN3-related neurodevelopmental disorder present with neurodevelopmental phenotype, often accompanied by additional neurological and neuroanatomical findings. Clinical severity can vary depending on variant type (homozygous loss-of-function vs heterozygous missense).
Main clinical features
• Global developmental delay / intellectual disability: Present in all reported individuals, with variable severity.
• Structural brain abnormalities (on MRI): Including partial or full agenesis of the corpus callosum, disorganized cerebellar folia, delayed myelination, decreased white matter volume, pons hypoplasia, and dysmorphic dentate nuclei.
• Seizures: Some individuals affected with structural brain abnormalities experience epilepsy, often requiring ongoing neurological care.
• Vision abnormalities: Includes strabismus, exotropia, hyperopia, esotropia, nystagmus, salt and pepper fundus pigmentation.
• Behavioral features: Mood disturbances, anxiety, hyperactivity, or other behavioral challenges.
• Hypotonia: Ranging from mild to severe.
• Progressive neurological decline: More pronounced in individuals with homozygous variants, with severe features of severe neurological disease.
• Dysmorphic features: Features including microcephaly, prominent forehead, hypertelorism, down-slanting palpebral fissures, full cheeks, and micrognathia have been described.
CLCN3