Rett syndrome

This disorder (Hagberg et al. 1983) is confined to girls and is due to an X-linked lethal mutation. It has a prevalence of approximately 1 : 12 500 (Hagberg 1985). Typically, the clinical features are of normal or near-normal development for the first 6 months to up to 3 years of age, when purposive hand movements are lost, with the appearance of stereotyped wringing movements or sucking of the hands. Dementia, usually profound and with autistic features, develops rapidly with, at a later stage, development of pyramidal and extrapyramidal signs, often with kyphoscoliosis. Secondary microcephaly occurs in those whose onset is early. Epilepsy with a characteristic EEG may be useful in diagnosis (Robb et al. 1989). Abnormal breathing patterns are commonly seen. The management is of all the multiple problems of these very disabled children who usually survive to adult life. Since the classic disease was recognized an increasing number of variants have been recognized, some with severe epilepsy and others with milder features and later onset. Until a diagnostic test is widely used, the extent of the clinical phenotype will not be clear (Hagberg 1993; Hagberg and Skjeldal 1994). The causative X-chromosome gene mutations in 80% of cases involve the methyl-CpG-binding protein 2 locus (Amir et al. 1999).