MECP2duplicationssyndrom

MECP2 duplication syndrome (MECP2DS) is a genetic disorder caused by duplication of the MECP2 gene on Xq28, leading to overexpression of the MeCP2 protein in neurons. It is an X-linked dominant condition in which affected males typically demonstrate more severe impairment, while females who carry the duplications often have milder or no symptoms due to skewed X-inactivation.

Clinical features usually appear in infancy and include generalized hypotonia, poor head control, feeding difficulties, and recurrent respiratory infections. Developmental delay is common, with little or no functional speech. Movement disorders such as spasticity, ataxia, tremor, and reduced motor milestones are frequent. Seizures occur in a substantial proportion of individuals. Other findings may include dysmorphic facial features, scoliosis, and progressive neurologic impairment.

Diagnosis is suspected from the early presentation and confirmed by genetic testing showing a copy-number gain duplicating MECP2 on Xq28. Array-based methods (array CGH or MLPA) are commonly used; standard sequencing may miss duplications. Parental testing helps distinguish de novo cases from maternally inherited duplications and informs genetic counseling.

Management is supportive and multidisciplinary. It focuses on improving feeding and growth, preventing and treating infections, and addressing motor, communication, and developmental needs through physical, occupational, and speech therapies. Seizures are treated with anticonvulsants when present. Regular medical follow-up and vaccination are important.

Prognosis is variable and generally reflects the degree of neurologic involvement. There is no cure, but research is exploring therapeutic approaches aimed at normalizing MECP2 dosage or function.