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Rett syndrome: Genetics, clinical features, and diagnosis

Rebecca J Schultz, PhD, RN, CPNP
Daniel G Glaze, MD
Section Editors
Marc C Patterson, MD, FRACP
Helen V Firth, DM, FRCP, DCH
Deputy Editor
John F Dashe, MD, PhD


Rett syndrome (RTT) is a neurodevelopmental disorder that occurs almost exclusively in females. It was described in 1966 by Andreas Rett, an Austrian pediatrician and neurologist [1]. After a brief period of initially normal development, affected patients experience loss of speech and purposeful hand use, stereotypic hand movements, and gait abnormalities. Additional features include deceleration of head growth, seizures, autistic features, and breathing abnormalities [2]. Most cases result from mutations in the MECP2 gene [3].

This topic will review the genetics, clinical features, and diagnosis of Rett syndrome. The treatment and prognosis are reviewed elsewhere. (See "Rett syndrome: Treatment and prognosis".)

Autism spectrum disorders are discussed separately. (See "Autism spectrum disorder: Terminology, epidemiology, and pathogenesis" and "Autism spectrum disorder: Clinical features" and "Autism spectrum disorder: Diagnosis".)


In the majority of patients, RTT is caused by mutations in the MECP2 gene, which maps to Xq28 and encodes methyl-CpG binding protein 2 (MeCP2) [3]. Although MeCP2 is expressed in all tissues, it is most abundant in the brain, which may be more sensitive to abnormal MeCP2 than other tissues. Mutations in MECP2 have been detected in approximately 95 percent of classic sporadic RTT cases and 75 percent of atypical RTT cases [4,5]. A minority of patients have atypical RTT caused by mutations in CDLK5 or FOXG1 genes. (See 'Classification and major features' below and 'Atypical RTT' below.)

Three types of MECP2 mutations occur: missense, frameshift, and nonsense. The type of mutation may affect phenotypic expression. (See 'Genotype-phenotype correlations' below.)

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Literature review current through: Sep 2017. | This topic last updated: Feb 02, 2017.
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