Rett syndrome is an X-linked dominant neurodevelopmental disorder manifesting with severe intellectual disability in females caused by various mutations in the MECP2 gene.
Rett syndrome (RTT) is a pervasive neurodevelopmental disorder mainly caused by mutations in the X-linked MECP2 gene associated with severe intellectual disability, movement disorders, and autistic-like behaviors.
Duplications of the X-linked MECP2 gene are associated with moderate to severe intellectual disability, epilepsy, and neuropsychiatric illness in males, while triplications are associated with a more severe phenotype.
Duplications encompassing the MECP2 gene on the Xq28 region have been described in male patients with moderate to severe mental retardation, absent speech, neonatal hypotonia, progressive spasticity and/or ataxia, recurrent severe respiratory infections, gastrointestinal problems, mild facial dysmorphisms (midface hypoplasia, depressed nasal bridge, large ears) and epilepsy.
Xq28 duplications including MECP2 are a well-known cause of severe mental retardation in males with seizures, muscular hypotonia, progressive spasticity, poor speech and recurrent infections that often lead to early death.
We propose to implement DNA copy number testing for MECP2 in the current diagnostic testing in all males with moderate to severe mental retardation accompanied by (progressive) neurological symptoms.
MECP2 mutations have subsequently been identified in patients with a variety of clinical syndromes ranging from mild learning disability in females to severe mental retardation, seizures, ataxia, and sometimes neonatal encephalopathy in males.
However, the recent identification of mutations in the MECP2 gene in affected males indicates that screening of the MECP2 gene should be considered also in males with severe mental retardation (MR) in whom the most common forms of MR have been excluded.
The two males and the two obligate carrier females presented a mutation in the MECP2 gene, demonstrating that, in males, MECP2 can be responsible for severe mental retardation associated with neurological disorders.