MECP2 duplication as a cause of mental retardation and neurological impairment in males. Case report.

The loss of MECP2 gene function in Xq28 is associated to Rett’s syndrome in females and to syndromic and non-syndromic mental retardation (MR) in males. Array CGH analysis showed that MECP2 duplication determines a phenotype characterized by MR, hypotonia, progressive spasticity, absence of speech, recurrent respiratory infections and seizures (Van Hesch, 2005). To date a small number of affected males have been reported, probably due to the recent discovery of the syndrome and to phenotype variability resulting from the size of the duplicated region (Xq28 contains several genes besides MECP2). We observed a 2y8m-old male, firstborn following normal pregnancy. Neurological examination: hypotonia, hypomimia, drooling, ataxia with initial independent walking, poor relationship, absence of speech. Age at Bayley Scale: 12m. Cranial MRI: delayed myelination. EEG: abnormalities during sleep. At the age of 3, severe bronchopneumonia. Slight improvement of neuropsychic competences was observed during subsequent examinations. At the age of 4, array-CGH revealed MECP2 and IRAK1 duplication of Xq28 (this picture is associated to a milder phenotype than one with a larger duplication). Carrier testing demonstrated that the mother is heterozygote for the same duplication. During a second pregnancy, prenatal testing revealed that this male fetus was also affected.