Clinical features

The uncertainty of diagnosis associated with the occasional presence of apparently affected males has always been complicated by the wide clinical spectrum presented by females, which ranges from the severely affected “classical” cases through a wide range of disability to a milder forme fruste. This variable severity has been partly ascribed to the degree to which skewing of X inactivation favours expression of the normal X chromosome. This, however, may not explain the specific variants such as the more mildly affected girls with retained speech or the more severe congenitally affected cases with early seizures.

Classically, Rett syndrome may be diagnosed when an affected girl has developed normally for about the first 6 to 18 months of life. At about this age her development begins to slow down and then regresses, with loss of skills already gained, such as speech and purposeful movement of the hands. Affected girls become subject to gross developmental delay, severe mental handicap, stereotyped hand movements such as hand wringing and flapping, an apraxic gait, and autistic behaviour.4 There may also be acquired microcephaly, periods of hyperventilation, and difficulties with swallowing.5 Finally, the regression period plateaus and affected girls survive into adulthood without further deterioration. Table 1 summarises the criteria by which a clinical …