Validity of clinical versus genetic study for identification of the fragile X syndrome

ABSTRACT

Fragile X syndrome is the most common cause of idiopathic X linked mental retardation among boys. It presents several diagnostic problems due to variable clinical features. Inconsistencies also exist in both cytogenetic and molecular markers. This study was conducted on 100 males referred for mental retardation of unknown cause at the Alexandria University Children's Hospital with an age three years and older. The study population was screened for clinical detection of Fragile X syndrome using Ten-item checklist. Patients with positive checklist were subjected to cytogenetic analysis to detect the fragile site on X chromosome and molecular analysis for detection of the altered DNA sequence using polymerize chain reaction [PCR].The patients' ages ranged 3-14 years with a mean of 5.99 +/- 2.68 years. Their IQs ranged 33-85 with a mean of 60.22 +/- 14.05. Out of the 100 males, 22 cases scored positive on the checklist. The most frequent clinical characteristic was hyperactivity [50%] and the least frequent was macro-orchids [2%]. Cytogenic analysis was positive for the fragile site at Xq 27.3 for four cases [18.2%] and negative for 18 cases [81.8%].PCR was positive [more than 200 CGG repeats] for 7 cases [31.8%] and negative for 15 cases [68.2%]. Also, there was a highly significant correlation between the score of the checklist and the positivist of both tests [P=0.01 for each test]. In conclusion, pre-test selection based on clinical criteria is useful to identify high-risk groups and minimizes the cost-effectiveness of both cytogenesis and molecular laboratory testing of fragile X syndrome. Combination of behavioral and physical characteristics is valuable especially in pre-pubertal cases