MECP2-Duplication Syndrome

Lubs X-Linked Mental Retardation Syndrome, MRXSL

Klinische Symptomatik

Duplications in Xq28 involving the methyl CpG binding protein 2 gene (MECP2) have been described only in male patients males manifesting a progressive neurodevelopmental syndrome. (Deletions and mutations of MECP2 are associated with Rett Syndrome.) Because MECP2 is located on the X chromosome and affected patients do not exhibit specific dysmorphic features the disease is classified as NS-XLMR (non syndromic X-linked mental retardation). Female carriers usually are asymptomatic.

 

Clinical features are:

• postpartal und infantile hypotonia
• swallowing problems
• slow motor development
• progressive spasticity predominantly of lower limbs
• severe mental retardation, without any or loss of speech
• proneness to infections, mainly respiratory
• epilepsy (50%), mostly generalised, possibly atonic or absence seizures
• no walking in about 30% , if walking ataxic gait
• mild facial dysmorphias:
  • brachycephaly
  • midface hypoplasia
  • large ears
• bodyhight und headcircumference usually normal (except in very large deletions, here possibly also urogenital abnormalities)
• Limited life expectancy in 50%, presumably due to recurrent severe infections
• Rare symptoms:
  • constipation
  • corpus callosum hypoplasia
  • stereotyped hand movements

Genetik

The the methyl CpG binding protein 2 gene (MECP2) is located on chromosome Xq28. The duplication affects 0,3 - 2,3 Mb. Additional clinical symptoms may be present in patients with rarely ocurring larger deletions. For affected males there is a 100% penetrance. Most females heterozygous for MECP2 duplication show extreme to complete skewing of X-chromosome inactivation and thus are asymptomatic.

Häufigkeit

No reliable data so far

 

Diagnostik