Rett like syndrome
Atypical Rett syndrome
Type of disease: Rare conditions
Atypical Rett syndrome is a neurodevelopmental disorder that is diagnosed when a child presents with a Rett-like syndrome but does not fulfill all the diagnostic criteria for typical Rett syndrome. Like classic Rett syndrome, atypical Rett syndrome predominantly affects girls. Atypical forms may present with either a milder or more severe clinical picture than that seen in typical Rett syndrome. Several subvariants of atypical Rett syndrome have been defined:
- The early-onset seizure type is characterized by seizures in the first months of life with subsequent development of Rett features (including developmental problems, loss of language skills, and repeated hand wringing or hand washing movements). It is frequently caused by mutations in the X-linked CDKL5 gene (Xp22).
- The congenital variant is the most severe form of atypical Rett syndrome, with onset of classic Rett features during the first three months of life. This variant is generally caused by mutations in the FOXG1 gene (14q11-q13).
- The forme fruste is a milder variant with onset in early childhood and an incomplete and prolonged course.
- The late childhood regression form is characterized by a normal head circumference and by a more gradual and later onset (late childhood) regression of language and motor skills.
- The preserved speech variant is marked by recovery of some verbal and manual skills and is caused in at least some cases by mutations in the MECP2 (Xq28) gene, which is also responsible for the majority of cases of classic Rett syndrome.
Diagnosis relies on clinical evaluation using the diagnostic criteria for atypical Rett syndrome which was defined by Hagberg in 1994. Molecular analysis may allow confirmation of the diagnosis. Source: Genetic and Rare Diseases Information Center (GARD), supported by ORDR-NCATS and NHGRI.