Specific atypicality in preserved speech variant?

Abstract

Introduction Rett syndrome, caused by mutations in the gene MECP2 for methyl‐CpG‐binding protein 2, begins in seemingly normal 6‐ to 18‐month‐old children. MECP2 is primarily expressed in the brain, in neurons, when they become functionally mature, and before synaptogenesis. Classic Rett syndrome has been reported in one in 10,000 females, and the atypical form (variants), implying the absence of one or more expected signs, in as many as one in 5000 females. The main issues addressed refer to the developmental course and its early (specific) signs of a rare atypical form of Rett, the Preserved Speech Variant. Methods Case report: One girl with a MECP2 mutation (del(378‐43)‐964 ins965GA) meeting clinical criteria for Preserved Speech Variant, was longitudinally observed from 6 months to 10 years of age. As the diagnosis was approved by mutation testing at the girl's age of 4 years, we retrospectively analysed family videos and the clinical history up to this age. Furthermore, we prospectively applied the following methods up to 10 years: the Austrian Rett Survey; behavioural observation in her natural surroundings (video data); assessment of severity in Rett syndrome; optimality questionnaires; Austrian Communicative Development Inventories; spontaneous speech samples; language development tests. Results Episodic events of atypical and stereotyped motor and (pre‐)linguistic behaviour increased over time and became predominant at two years of age, the onset of regression. A peculiar quality of early motor patterns as well as communicative idiosyncrasies were among the deviant patterns observed. Discussion The comprehensive analyses suggest a qualitative deviation already during the pre‐regression period that impacts on the entire developing neuro‐cognitive system. The unique possibility to “look back” gives new insights into the genetic interference with normal brain development.