Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

You are here: Molecular Genetics » Rett Syndrome (RTT)

Rett Syndrome (RTT) [F84.2]

OMIM numbers: 312750, 300005 (MECP2)

Dr. rer. biol. hum. Soheyla Chahrokh-Zadeh, Dr. med. Imma Rost

Scientific Background

The Rett syndrome is an X chromosomal dominant neurodegenerative disease (frequency 1 in 10,000), which mainly occurs in females. After normal development, the children typically lose already acquired skills between the 6th and 18th month of life, especially skills such as using the hands purposefully, social interaction and speech. A major sign is development of stereotypic hand movements. Other signs and symptoms include growth impairment, microcephaly, gait ataxia, episodes of apnea or hyperpnea, sleeping difficulties, increasing scoliosis and seizures. The small number of affected boys predominantly displays severe neonatal encephalopathy.

The disease is caused by mutations in the MECP2 gene, which encodes a protein involved in the regulation of gene expression by methylation. Severity of the disease is influenced by the pattern of the X inactivation and type of mutation. Most mutations are de novo; therefore, the recurrence risk is low. In some rare cases, the mutation is present in combination with a non-random X-inactivation in mothers who do not display any clinical signs or symptoms; therefore, examination of the mother of an affected child is indicated. Since germ cell mosaics are occasionally observed, prenatal diagnostics may be indicated also if no mutation is detected in the mother. Some patients suffering from the non-classical form of the Rett syndrome, which is characterized by early onset of seizures, have mutations in the CDKL5 gene.