Background-Submicroscopic subtelomeric chromosome defects have been found in 7.4% of children with moderate to severe mental retardation and in 0.5% of children with mild retardation. EVective clinical preselection is essential because of the technical complexities and cost of screening for subtelomere deletions. Methods-We studied 29 patients with a known subtelomeric defect and assessed clinical variables concerning birth history, facial dysmorphism, congenital malformations, and family history. Controls were 110 children with mental retardation of unknown aetiology with normal G banded karyotype and no detectable 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 history 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 mothers of subtelomeric cases compared to 30% of controls (p=0.028) which was, however, not significant after a Bonferroni correction. Common features (>30%) among subtelomeric deletion cases were microcephaly, short stature, hypertelorism, 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 diVerent from the controls. Using the results, a five item checklist was developed which allowed exclusion from further testing in 20% of the mentally retarded children (95% CI 13-28%) in our study without missing any subtelomere cases. As our control group was selected for the "chromosomal phenotype", the specificity of the checklist is likely to be higher in an unselected group of mentally retarded subjects. Conclusions-Our results suggest that good indicators for subtelomeric defects are prenatal onset of growth retardation and a positive family history for mental retardation. These clinical criteria, in addition to features suggestive of a chromosomal phenotype, resulted in the development of a five item checklist which will improve the diagnostic pick up rate of subtelomeric defects among mentally retarded subjects. (J Med Genet 2001;38:145-150)

8912 Shekelle RB, Schoenberger JA, Stamler J. Correlates of the JAS type A behavior pattern score. J ChronicDis 1976;29:381-94. 13 Haynes SG, Feinleib M, Levine S, Scotch N, Kannel WB. The relationship ofpsychosocial factors to coronary heart disease in the Framingham study II. Prevalence of coronary heart disease.

SUMMARY Three cases are reported of a lethal multiple congenital anomaly syndrome. The infants had moderate limb shortening, joint contractures, polydactyly, and the two with male karyotypes had female external genitalia. Internal anomalies included unilobular lungs, hypoplasia of the anterior portion of the tongue, and renal hypoplasia.We report three unrelated infants with a lethal multiple congenital anomaly (MCA) syndrome who had moderately short limbs, polydactyly, and valgus deformity of the feet with syndactyly. All had female external genitalia but two had 46,XY karyotypes. All This apparently female infant was born at 35 weeks' gestation, the first child of a healthy, unrelated, Caucasian 26 year old woman and 30 year old man. The mother had had a healthy baby and a termination of pregnancy in a previous relationship. In this pregnancy urinary and serum oestriols were low when measured between 32 and 35 weeks' gestation, but human placental lactogens were normal. The baby, which had female external genitalia, died of respiratory failure at the age of 11/2 hours.The baby weighed 2*325 g, length 45 cm, occipito-

Nineteen patients were analysed by fluorescence in situ hybridisation (FISH) with selected lIpl3 markers. They were examined because they had either isolated sporadic or familial aniridia, or aniridia with one or more of the WAGR (Wilms' tumour, aniridia, genital anomalies, and mental retardation) syndrome anomalies. The FISH markers from distal lIpl3 were cosmids F02121, PAX6 (aniridia), DllS324, and WT1 (Wilms' tumour predisposition). Two of the patients with isolated aniridia were abnormal, one with an apparently balanced reciprocal 7;11 translocation and an 1ipi3 breakpoint, which by FISH was shown to be -30 kb distal to the aniridia (PAX6) gene, and the other had a submicroscopic deletion involving part of PAX6 that extended distally for -245 kb. Two patients with aniridia together with other WAGR malformations had deletions involving all four cosmids. One case with aniridia associated with developmental and growth delay had a deletion including F02121 and PAX6 but not DI1S324 and WT1, while in a further case the deletion included all four test cosmids. These studies show that a combined conventional and molecular cytogenetic approach to patients presenting with aniridia is a useful method for differentiating between those with deletions extending into and including WT1 and therefore between those with high and low risks of developing Wilms' tumour.