Short fourth toes in Rett syndrome: a biological indicator

Classic Rett syndrome is now well-known as a non-dysmorphic developmental disorder almost certainly of genetic origin. Short 4th toe (uni- or bi-lateral) is inherited as an autosomal dominant with 27% penetrance and is found also in certain dysmorphic syndromes. Having observed the anomaly in several Rett cases, we examined a cohort of classic Rett people at advisory clinics and all the residents in an adult learning disabled hospital in order to determine the significance of the association. Among the Rett clinic group 28 of 137 showed the anomaly (20%). Among the heterogeneous hospital group it was found in 19 of 526 people, 9 of 206 females (4%) and 10 of 320 males (3%). Rett syndrome was present in 7% of all the women (14 of 206 women). Four of the Rett women showed the toe anomaly (28% of the Rett cases). The anomaly was found in 4 men and 4 women with Down syndrome, representing 16% (8 of 49). Diagnoses in other men with the anomaly included foetal alcohol syndrome, toxoplasmosis, 18/2 translocation and birth injury. The only other woman with the anomaly was profoundly disabled with short limbs. The strong positive association of the anomaly with Rett syndrome and Down syndrome throws new light on the developmental processes affected by these diseases.