No abstract

Historical, physical, cognitive, and cytogenetic data were documented in 105 heterozygous fragile X [fra(X)] females and 90 controls in a prospective fashion. For comparisons, we divided heterozygotes and controls into those with cognitive impairment (IQ less than 85) and normal IQ (IQ greater than or equal to 85). The only finding that was significantly more frequent in impaired heterozygotes compared with impaired controls chi 2 analysis was shyness. Features that were more frequent in normal IQ heterozygotes compared with normal controls were voluntary thumb dislocation and hyperextensible metacarpal-phalangeal (MP) joints. Comparisons among heterozygotes demonstrated more math problems, hand biting, strabismus, high-arched palate, hyperextensible finger joints, and flat feet in impaired heterozygotes than in normal heterozygotes. Premature menopause was present in 8 of 61 normal heterozygotes and in none of the impaired heterozygotes. A multiple regression analysis demonstrated a significant inverse correlation between the percent fragility and IQ for the heterozygotes as a group. However, no correlation existed between IQ and fragility when the percent fragility was 2% or greater. However, a higher percentage of fragility was positively correlated with the total number of physical findings present.

Attentional deficits and hyperactivity frequently are major problems for fra(X) boys. This study evaluated the effectiveness of 2 stimulant medications, methylphenidate and dextroamphetamine compared to placebo in 15 children (13 males, 2 females) with the fra(X) syndrome. A double-blind crossover design was used with outcome measures which included parent and teacher behavior checklists, a controlled observation period, continuous performance tasks and an actometer measure of movement. When the children were treated with methylphenidate only, improvement was seen in socialization skills and attention span according to teacher checklists. Ten children were clinically considered responders and treatment was continued after the study was completed.

Previous studies have reported a drop of IQ in males with Martin-Bell or fragile X syndrome during childhood and adolescence. It is uncertain when and why this drop occurs and whether it affects all fragile X males. We have analyzed longitudinal IQ data on all 24 fragile X males who have been followed for at least 2 years through the Child Development Unit in Denver and who have been evaluated with a Stanford-Binet Form L-M assessment. A significant drop in IQ occurred for the group as a whole, but an individual z analysis demonstrated that only 7 of 24 had a significant decline in IQ. Visual inspection demonstrates an initial decline in IQ beginning in middle childhood and continuing through adolescence. We postulate that this drop occurs because of relatively greater weaknesses with abstract reasoning and higher symbolic language skills that are stressed in the cognitive testing of later childhood and adolescence.