Cognitive and behavioral profile of fragile X boys: Correlations to molecular data

Fragile X syndrome (FXS) is the most common form of inherited mental retard ation after Down syndrome. The expansion of a CGG repeat, located in the 5' -untranslated region (5'-UTR) of the FMR1 (fragile X mental retardation) ge ne, leads to the hypermethylation of the repeat and the upstream CpG island . Methylation is associated with transcriptional silencing of the FMR1 gene . The lack of FMR1 protein is believed to be responsible for the typical ph ysical and mental characteristics of the syndrome. To analyze the specific phenotype of that syndrome as well as possible associations between the phe notype and the genotype, we examined a group of 49 fragile X boys and a con trol group of 16 patients with tuberous sclerosis, To determine the cogniti ve and behavioral phenotype, the Kaufman Assessment Battery for Children (K -ABC), the Child Behavior Checklist (4/18), and a structured psychiatric in terview (Kinder DIPS) were used. The genotype was analyzed by the Southern blot method. The phenotype of boys with FXS is characterized by a specific cognitive profile with strengths in acquired knowledge and in simultaneous processing. The psychiatric comorbidity is high and ADHD (attention deficit hyperactivity disorder), oppositional defiant disorder, enuresis, and enco presis predominate. In a group of 24 fragile X boys, no significant correla tions between the specific aspects of the phenotype and the genotype were f ound. (C) 2000 Wiley-Liss, Inc.