MECP2-Related Disorders - Classic or Atypical Rett Syndrome
MECP2-related disorders include classic Rett syndrome, atypical (or variant) Rett syndrome, and mild learning disabilities. Classic Rett syndrome is a rare, severe, X-linked neurodevelopmental disorder that most frequently affects females. It is characterized by normal development in the first 6-18 months of life, followed by regression of language and motor skills. Other features include stereotypic hand movements, intellectual disability, autistic characteristics, microcephaly, and seizures. In males, the disease presents as MECP2-related severe neonatal encephalopathy, with intellectual disability and death typically occurring before 2 years of age. Rett syndrome usually occurs as the result of a de novo mutation in the MECP2 gene, although inherited forms do exist. A rare neuropsychiatric phenotype that results from MECP2 duplications has also been documented. The clinical severity of MECP2 disorders is influenced by the specific MECP2 variant, and in females, the pattern of X inactivation. MECP2 genetic testing is used to confirm a clinical diagnosis and to determine recurrence risk; however, a negative molecular result does not exclude a diagnosis of classic Rett syndrome.
Last Update: June 2019