A possible association between genotypes and early signs of Rett disorder

Abstract

Introduction: An apparently normal early development was one of the initial criteria for classic Rett syndrome. However, several investigators considered Rett syndrome to be a developmental disorder manifesting very soon after birth. Different types and positions of the MECP2 mutations and a variable pattern of x-inactivation contribute to the range of severity of this disorder. Methods: Videos of 32 Rett cases of various genotypes were carefully assessed for movements, posture and behaviour during the first 6 months of life. All signs, which deviated from the normal standard, were recorded meticulously. Special attention was paid to the face, the hands and to body movements. Results: A detailed analysis clearly demonstrated the following early abnormal signs: long lasting tongue protrusion, asymmetric eye opening and closing, bursts of abnormal facial expressions, bizarre smile, abnormal finger movements, hand stereotypies, an abnormal quality of general movements, postural stiffness, tremor and stereotyped body movements. R168X and R255 mutations were associated with the earliest onset (first days of life) of these abnormal signs. Discussion: Rett disorder is manifest within the first months of life. Those MECP2 mutations associated with the most severe clinical phenotype were also associated with an earlier onset of abnormal signs. (FWF P19581-B02, Lanyar Foundation P325).