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

Abstract

Fragile X syndrome (FXS) is the most common form of inherited mental retardation after Down syndrome. The expansion of a CGG repeat, located in the 5'-untranslated region (5'-UTR) of the FMR1 (fragile X mental retardation) gene, 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 physical and mental characteristics of the syndrome. To analyze the specific phenotype of that syndrome as well as possible associations between the phenotype and the genotype, we examined a group of 49 fragile X boys and a control group of 16 patients with tuberous sclerosis. To determine the cognitive and behavioral phenotype, the Kaufman Assessment Battery for Children (K-ABC), the Child Behavior Checklist (4/18), and a structured psychiatric interview (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 encopresis predominate. In a group of 24 fragile X boys, no significant correlations between the specific aspects of the phenotype and the genotype were found.

The Prevalence and Phenomenology of Repetitive Behavior in Genetic Syndromes

“…These findings are consistent with previous studies of repetitive behavior in Fragile X syndrome (Backes et al, 2000;Hagerman & Lampe, 1999;Hagerman et al, 1986;Mazzocco et al, 1998), which provides some information about the validity of the Repetitive Behaviour…”

“…In Fragile X syndrome there is a heightened prevalence of both of these subtypes of repetitive behavior (Backes et al, 2000;Hagerman & Lampe, 1999;Mazzocco et al, 1998), suggesting a generalised heightened probability of repetitive behavior. Describing the nature of these different profiles in detail using a consistent measure of repetitive behavior across groups will enable further insight into the causal factors that underlie these differences.…”

Rescue of fragile X syndrome phenotypes in Fmr1 KO mice by the small-molecule PAK inhibitor FRAX486

“…FRAX486 had a remarkable effect, decreasing seizure susceptibility from 100% to 25% in Fmr1 KO mice. Next, three-quarters of people with FXS also have attention deficit and hyperactivity disorder (43,44). This symptom, modeled in mice by hyperactivity in the open field, was also reversed by FRAX486.…”

FMR1 and the fragile X syndrome: Human genome epidemiology review

“…For example, size of the methylated full mutation is not correlated with IQ or related to the occurrence other specific characteristics of affected males such as attention-deficit/hyperactivity disorder. 88 Also, while the low but measurable level of FMRP seems to be related to level of development among affected males, it does not seem to be related to the rate of development or to the expression of autism. 89 In fact, the co-occurrence of autistic behavior and the fragile X syndrome more accurately predicts developmental status than does the level of FMRP, 89 possibly suggesting the existence of additional factors involved in the fragile X phenotype.…”