EHMT2-related Kleefstra-like Syndrome

EHMT2-related Kleefstra-like Syndrome is an emerging neurodevelopmental disorder that phenocopies key features of Kleefstra syndrome, including developmental delay or intellectual disability, severe speech impairment, hypotonia, behavioral abnormalities, dysmorphic features and variable congenital anomalies. More info

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Genetics

This pipeline entry refers to pathogenic EHMT2 variants, not classic EHMT1-related Kleefstra syndrome. De novo heterozygous catalytic-domain variants support an autosomal dominant disorder; very rare biallelic loss-of-function cases have also been reported.

Molecular Mechanism

EHMT2 (G9a) forms a histone H3 lysine-9 methyltransferase complex with EHMT1. Disease-associated variants impair nucleosomal methylation and transcriptional repression; catalytically inactive complexes may exert dominant-negative effects on chromatin regulation during neurodevelopment.

Therapy

Treatment is supportive and individualized, including developmental, communication, behavioral, neurologic and organ-specific care. No disease-modifying treatment is established for EHMT2-related disease.

CCP Activity

CCP has developed and characterized an EHMT2 disease model to define neurodevelopmental, behavioral and systemic phenotypes and to establish molecular readouts of altered H3K9 methylation suitable for future therapeutic testing.

Mouse Models Mouse Models & Gene Cards

This section is currently in development.