A SIMPLIFIED 6-ITEM CHECKLIST FOR SCREENING FOR FRAGILE-X SYNDROME INTHE PEDIATRIC POPULATION

Objective: In our general experience, about 2% of samples referred for fragile X testing showed positive results on Southern blot analysis. The aim of this project was to determine whether screening criteria co uld be developed to increase the proportion of positive test results w ithout sacrificing sensitivity. Study design: We retrospectively analy zed nine clinical characteristics from patient records of 273 male and 62 female pediatric probands (average age, 5.7 years) referred for fr agile X testing. The characteristics included mental retardation, fami ly history of mental retardation, large or prominent ears, elongated f ace, attention deficit hyperactivity disorder, autistic-like behavior, simian crease, macroorchidism, and hyperextensible joints. These were scored as 2 if present, 1 if borderline present, and 0 if absent. Res ults: Analysis of the nine characteristics identified three (simian cr ease, macroorchidism, and hyperextensible joints) with low frequency a nd statistical insignificance, which were therefore eliminated. With t he use of the remaining six characteristics, if a score of 5 or more w as used as the criterion for requesting fragile X testing, then close to 60% of those tests from our patient population could have been elim inated without missing any positive cases. The validity of our thresho ld score of 5 was subsequently confirmed among an additional six cases of fragile X syndrome. Conclusion: With our simplified six-item clini cal checklist, 60% of testing could have been eliminated, thereby impr oving the cost-effectiveness of fragile X testing and increasing the p roportion of Cases with positive results by threefold.