Atypical Rett syndrome

Atypical Rett syndrome is a neurodevelopmental disorder that is diagnosed when a child has some of the symptoms of Rett syndrome but does not meet all the diagnostic criteria. Like the classic form of Rett syndrome, atypical Rett syndrome mostly affects girls. Children with atypical Rett syndrome can have symptoms that are either milder or more severe than those seen in Rett syndrome. Several subtypes of atypical Rett syndrome have been defined:

• The early-onset seizure type is characterized by seizures in the first months of life with later 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 genetic testing may confirm the diagnosis.

Treatment is symptomatic and supportive. Medication may be needed for breathing irregularities, sleep disturbances (melatonin), agitation (risperidone), rigidity and motor difficulties (levodopa and carbidopa), and to control seizures (antiepileptic drugs). Anti-reflux agents may also be required.