Phenotypic heterogeneity of growth and psychometric intelligence in Prader-Willi syndrome: Variable expression of a contiguous gene syndrome or parent-child resemblance?

Phenotypic variability in children with Prader-Willi syndrome (PWS) was inv estigated with respect to variable expression of the contiguous gene syndro me and trait variance. In a prospective study, parent/child resemblance of anthropometric and psychometric measures was analyzed in 22 children with P WS (11 females and 11 males; 18 deletions, 4 uniparental disomy (UPD)) and in a control group (88 females and 88 males). The average child-midparent Z -score difference for height in females was -1.9 and in males -0.9, head ci rcumference -1.7 and -1.0, and body mass index (BMI) 2.3 and 2.7, respectiv ely. Intellectual performance of females and males was, on average, -2.7 an d -2.6 below maternal performance, Range and standard deviation were modera tely increased for height and head circumference, doubled for BMI, and unch anged for IQ, Parent/child correlations for anthropometric and psychometric measurements in the study group did not significantly differ from those of the control group, Exceptions were higher correlations between mothers and daughters for height (P < 0.05) and BMI (P < 0.01), and lower correlations for head circumference between midparent values and daughters (P < 0.05) t han in the control group. In conclusion, parent-child resemblance in growth and intellectual development among children with PWS was found to be compa rable to that noted in the normal population, indicating a strong determina tion by trait variance. Children with PWS differed significantly with respe ct to a lower trait level and-with the exception of IQ-a larger variability . The latter may indicate a variable expression of the contiguous gene synd rome. (C) 2000 Wiley-Liss, Inc.