The spectrum of phenotypes in females with Rett Syndrome

Abstract

Since the discovery of mutations in the methyl-CpG binding protein-2 (MECP2) gene in Rett Syndrome (RTT) a large number of females have been diagnosed worldwide. In this article we present the clinical and developmental data of 120 RTT females with mutations in the MECP2 gene and individually describe typical and atypical cases. We found a broad spectrum of phenotypes in females. At the severest end we have females with primary developmental delay who never learned to turn, sit or walk and who developed severe epilepsy. At the mildest end of the spectrum, there are females with only minor neurological symptoms who have good gross motor function, speak and have relatively well-preserved hand function. A number of girls either do not fulfil all the necessary diagnostic criteria or present with symptoms that have not been described in RTT before. Comparing our data with the normal population we found that girls with RTT have a smaller occipito-frontal circumference, shorter length and lower weight at birth. As a result of molecular genetic analysis a broad spectrum of phenotypes in RTT females has evolved. We found evidence that the defect in MeCP2 influences the somatic growth before birth.