Atypical Rett Syndrome

Rett syndrome is a rare neurological disorder that almost exclusively affects girls. Classic or typical Rett syndrome is caused by mutations in a gene called MECP2, which encodes for a protein that plays a role in controlling the activity of other genes. Patients with classic Rett syndrome generally develop symptoms between the age 6 and 18 months.

There also are several types of atypical Rett syndrome, and about 30 percent of patients fall into this category.

What is atypical Rett syndrome?

A patient is said to have atypical Rett syndrome if their symptoms do not meet all the Rett syndrome diagnostic criteria. Atypical forms of the disease may be milder or more severe than typical Rett syndrome. Several subtypes of atypical Rett syndrome have been defined.

Early-onset seizure (Hanefeld variant)

The Hanefeld variant is characterized by seizures in the first few months of life, followed by typical Rett syndrome symptoms. This variant is caused by mutations in the CDKL5 gene, which encodes for a protein involved in the growth and development of nerve cells in the brain. One patient with a mutation in a gene called NTNG1 also has been reported.

Congenital variant (Rolando variant)

The Rolando variant is the most severe form of atypical Rett syndrome. Symptoms of classic Rett syndrome appear in the first three months of life in this variant. It is caused by mutations in the FOXG1 gene, which encodes for a transcription factor (a protein that regulates the activity of other genes).

Forme fruste variant

Forme fruste is a medical term used to refer to the incomplete manifestation of a disease. In atypical Rett syndrome, forme fruste refers to a milder variant with symptoms appearing in early childhood. Patients may not develop all of the symptoms of typical Rett syndrome, and the disease usually progresses more slowly.

Late childhood regression variant

This variant is characterized by normal head circumference and by a more gradual and late-onset (usually in late childhood) loss of language and motor skills than what is seen in typical Rett syndrome.

Preserved speech variant (Zapella variant)

The Zapella variant is a form of Rett syndrome in which patients recover some speech and motor skills. This recovery does not occur in typical Rett syndrome. Some cases of this variant have been shown to also be caused by mutations in MECP2, the gene most commonly mutated in classic Rett syndrome.