Rett syndrome

Anita Datta MD (Dr. Datta of the University of British Columbia has no relevant financial relationships to disclose.)
Qi Xu MD (Dr. Xu of the University of British Columbia has no relevant financial relationships to disclose.)
Harvey B Sarnat MD FRCPC MS, editor. (Dr. Sarnat of the University of Calgary has no relevant financial relationships to disclose.)
Originally released November 3, 2014; last updated May 2, 2016; expires May 2, 2019

Overview

Rett syndrome is a rare genetic neurologic disorder of the grey matter of the brain that primarily affects females but has also been found in male patients. The incidence is 0.5 to 1 per 10,000 live female births (Laurvick et al 2006a; Fehr et al 2011). The clinical features include deceleration of the rate of head growth and a period of regression followed by stagnation or stabilization. Repetitive and stereotyped hand movements, such as wringing, are seen. There is usually loss of expressive language. Those affected with Rett syndrome require multidisciplinary care as many systems can be involved. Up to 80% of individuals with Rett syndrome will have seizures. Scoliosis, growth failure, and constipation are very common and can be problematic.

Key points

 

• Rett syndrome is a neurodevelopmental disorder with an incidence of 0.5 to 1 per 10,000 live female births that contributes significantly to severe intellectual disability in females worldwide.

 

• Patients with Rett syndrome present with loss of purposeful hand movements, partial or complete loss of expressive language, and stereotypical nonpurposeful hand movements.

 

• Patients with Rett syndrome usually present with a period of regression followed by some recovery or stabilization.

 

• Ninety percent of cases of Rett syndrome are secondary to methyl-CpG-binding protein 2 (MECP2) mutations. However, other mutations related to cyclin-dependent kinase-like 5 (CDKL5) and forkhead box protein G1 (FOXG1) have been identified.

 

• Genetic testing has dramatically affected the pattern and timing of diagnosis of Rett syndrome. It has further characterized the phenotype.

 

• Management of Rett syndrome requires a multi-disciplinary approach as many systems can be involved.

Historical note and terminology

Rett syndrome (OMIM 312750) was identified and published in 1966 by Dr. Andreas Rett, an Austrian physician. In 1954, he first noticed this syndrome in 2 girls as they sat in his waiting room with their mothers. He observed repetitive hand-washing motions. He found similarities when comparing developmental and clinical histories (Rett 1966).

In 1960, Dr. Bengt Hagberg in Sweden collected clinical records of girls with similar symptoms. In 1983, Dr. Hagberg published findings in the mainstream English journal, Annals of Neurology (Hagberg et al 1983). It was not until the second article about the disorder was published that Rett syndrome was generally recognized. Dr. Hagberg and Dr. Witt-Engerström developed a staging system in evaluation of Rett syndrome in 1986 (Hagberg and Witt-Engerstrom 1986).

The clinical criteria for the diagnosis of Rett syndrome have undergone multiple revisions, with the latest being published in 2010 (Neul et al 2010).

In 1999, Zoghbi and her team identified mutations in the X-linked gene, methyl-CpG-binding protein (MECP2) that lead to most cases of Rett syndrome (Amir et al 1999).

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