Diagnosis of Rett syndrome: can a radiograph help?

Abstract

Rett syndrome (RS), a neurodevelopmental disorder almost exclusively affecting girls, is associated with severe intellectual and motor disability. In the absence of biological markers, diagnosis is determined by a set of clinical criteria. In a previous study in Scotland, shortening of the fourth metatarsal was reported clinically in 20% of classical RS cases aged 5 years or older. The Australian Rett Syndrome Study database has facilitated a population-based radiological study of the hands and feet of girls with RS. Straight radiographs of hands and feet were available from 94 cases, representing 70.1% of the known RS population in Australia. Control radiographs were matched for age, sex, and laterality. Relative shortening of the fourth metacarpal/metatarsal was assessed using the sign method. A short ulna (negative ulna variance) was defined as the distal articular surface of the ulna being at least 5mm proximal to the distal articular surface of the radius. A positive metacarpal sign was twice as common in verified cases of RS than in controls in the right but not the left hand. A short ulna was more common in subjects with RS than in controls. A short fourth metatarsal was also more common among subjects with RS. More than half (56.6%) the girls with RS over the age of 4 years had a negative ulnar variance in either wrist or a metatarsal sign in either foot. These findings will assist with the diagnosis of RS and may help direct research towards the location of the molecular defect.