X-linked intellectual disability, Najm type

X-linked intellectual disability, Najm type (also known as XLID-Najm type or lissencephaly X-linked type 2) is an extremely rare genetic disorder caused by mutations in the CASK gene (calcium/calmodulin-dependent serine protein kinase), located on the X chromosome. The condition is characterized by severe brain malformation, specifically microcephaly with pontine and cerebellar hypoplasia (MICPCH), and in some cases lissencephaly or pachygyria. The ICD-10 code Q04.3 reflects the associated brain malformations (other reduction deformities of the brain). The disorder primarily affects the central nervous system, leading to profound intellectual disability, severe developmental delay, and seizures. Affected individuals typically present in the neonatal or infantile period with microcephaly, hypotonia, and failure to achieve developmental milestones. The condition predominantly affects males more severely, though heterozygous females can also be significantly affected due to the nature of CASK mutations. Clinical features include severe to profound intellectual disability, epilepsy, disproportionate pontine and cerebellar hypoplasia visible on brain MRI, optic nerve hypoplasia, and sensorineural hearing loss. Some patients may also exhibit nystagmus and feeding difficulties. Growth retardation and dysmorphic facial features may be present in some cases. There is currently no cure or disease-specific treatment for X-linked intellectual disability, Najm type. Management is supportive and symptomatic, focusing on seizure control with antiepileptic medications, physical and occupational therapy to optimize motor function, speech therapy, nutritional support for feeding difficulties, and early intervention programs. Regular monitoring by a multidisciplinary team including neurologists, geneticists, ophthalmologists, and audiologists is recommended to address the various manifestations of the disease.

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