Screening of mentally handicapped Egyptian children for fragile X syndrome using clinical, cytogenetic and molecular approaches

Abstract

To screen children with idiopathic mental retardation (MR) using a clinical Ten-Item Checklist (TIC) and to analyze high-risk fragile X syndrome (FXS) cases by cytogenetic and molecular genetic techniques. This study was conducted on 192 children with idiopathic MR enrolled from Pediatric clinics of University Hospitals and MR institutes of Alexandria, Mansoura and Benha Governorates, Nile Delta, Egypt (age range 2–14 years). Clinical scoring for patients was done using TIC according to which patients were categorized either positive checklist with score higher than 5 or negative with score less than 5. Positive cases underwent cytogenetic analysis that provoke expression of fragile sites on chromosome X and molecular genetic analysis for detection of permutation among cases or their 1st degree relatives. Analyzing all cases: IQ ranged from 30 to 80%, family history of MR was found in 28.6% and consanguinity was positive in 26%. Positive checklist cases constituted 23.9% and remainder 76.1% were negative checklist. The most frequent items in positive cases were large prominent ears, hyper-extensible finger joints, hyperactivity, and large narrow face with less common macro-orchidism. A positive linear association was found between laboratory test positivity and TIC score being stronger with cytogenetic analysis compared to polymerase chain reaction (PCR) (P 0.001 and 0.02, respectively). Using TIC, 76.1% cases could be eliminated from the waiting list of genetics laboratories. The relatively weaker association of TIC score to PCR compared to cytogenetic analysis together with areas under receiver operating characteristic curve 0.743 and 0.814 respectively denote the higher accuracy and sensitivity of PCR analysis in final diagnosis of FXS.

Keywords

Fragile X syndrome - cytogenetics - molecular genetics - Egypt