Kleefstra syndrome

Kleefstra syndrome (also known as 9q34 deletion syndrome or 9q subtelomeric deletion syndrome) is a rare genetic neurodevelopmental disorder characterized primarily by intellectual disability, childhood hypotonia (low muscle tone), and a distinctive facial appearance. The condition is caused either by a microdeletion of the 9q34.3 chromosomal region or by loss-of-function mutations in the EHMT1 gene (euchromatic histone methyltransferase 1), which encodes a histone methyltransferase important for normal brain development and function. The syndrome affects multiple body systems. Neurological features include moderate to severe intellectual disability, speech and language delay (with expressive language often more severely affected), and behavioral characteristics such as autism spectrum features, apathy, and intermittent aggression. Seizures occur in a significant proportion of patients. The characteristic facial features include microcephaly, flat midface, hypertelorism, arched eyebrows, short nose with anteverted nares, everted lower lip, and a protruding tongue. Congenital heart defects are present in approximately 30-50% of individuals, with a range of structural anomalies reported. Other features may include renal and urogenital anomalies, hearing loss, obesity, and sleep disturbances. Some patients experience a regression-like phenotype in adolescence or adulthood, characterized by severe apathy, catatonia-like features, and behavioral deterioration. There is currently no cure or disease-specific treatment for Kleefstra syndrome. Management is supportive and multidisciplinary, involving early intervention programs, speech and occupational therapy, behavioral support, and monitoring for associated complications such as cardiac defects, epilepsy, and sleep apnea. Psychiatric symptoms, including catatonia-like episodes, may require careful pharmacological management. Regular developmental assessments and screening for comorbidities are essential components of long-term care.

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