DNA analysis of the fragile X syndrome in an at risk pediatric population in croatia: simple clinical preselection criteria can considerably improve the cost-effectiveness of fragile X screening studies.

Advances in understanding the molecular basis of the fragile X syndrome, the most common cause of inherited mental retardation, have elicited new prospects for population-based studies identifying affected individuals and fragile X families, thus contributing in prevention of the disease. In comparison with numerous fragile X screening studies where unselected groups of individuals with mental retardation, developmental delay, learning disability or autistic-like behaviour had been observed, we performed fragile X analysis on clinically preselected individuals. The group we studied consisted of 108 children with mental retardation of unknown cause or positive family history who had at least one physical and/or behavioural characteristic often observed among fragile X individuals. A relative high frequency of the fragile X positive cases (13% overall, 17.3% in males) was detected, suggesting that simple preselection criteria can considerably increase the proportion of fragile X-positive cases, and therefore, improve the cost-effectiveness of fragile X testing. Retrospective clinical analysis using a simplified six-item fragile X checklist confirmed that scoring criteria can be used to additionally preselect individuals at risk. Our results also indicate that this syndrome is underdiagnosed in Croatia and that a further effort must be made to detect unrecognised cases.