Clinical studies on submicroscopic subtelomeric rearrangements: a checklist

Background-Submicroscopic subtelomeric chromosome defects have been found i n 7.4% of children with moderate to severe mental retardation and in 0.5% o f children with mild retardation. Effective clinical preselection is essent ial because of the technical complexities and cost of screening for subtelo mere deletions. Methods-We studied 29 patients with a known subtelomeric defect and assesse d clinical variables concerning birth history, facial dysmorphism, congenit al malformations, and family history. Controls were 110 children with menta l retardation of unknown aetiology with normal G banded karyotype and no de tectable submicroscopic subtelomeric abnormalities. Results-Prenatal onset of growth retardation was found in 37% compared to 9 % of the controls (p<0.0005). A higher percentage of positive family histor y for mental retardation was reported in the study group than the controls (50% v 21%, p=0.002). Miscarriage(s) were observed in only 8% of the mother s of subtelomeric cases compared to 30% of controls (p=0.028) which was, ho wever, not significant after a Bonferroni correction. Common features (>30% ) among subtelomeric deletion cases were microcephaly, short stature, hyper telorism, nasal and ear anomalies, hand anomalies, and cryptorchidism. Two or more facial dysmorphic features were observed in 83% of the subtelomere patients. None of these features was significantly different from the contr ols. Using the results, a five item checklist was developed which allowed e xclusion from further testing in 20% of the mentally retarded children (95% CI 13-28%) in our study without missing any subtelomere cases. As our cont rol group was selected for the ((chromosomal phenotype)), the specificity o f the checklist is Likely to be higher in an unselected group of mentally r etarded subjects. Conclusions-Our results suggest that good indicators for subtelomeric defec ts are prenatal onset of growth retardation and a positive family history f or mental retardation. These clinical criteria, in addition to features sug gestive of a chromosomal phenotype, resulted in the development of a five i tem checklist which will improve the diagnostic pick up rate of subtelomeri c defects among mentally retarded subjects.