Hyperphagic short stature and Prader-Willi syndrome: A comparison of behavioural phenotypes, genotypes and indices of stress

Abstract

Background: The clinical features of hyperphagic short stature (HSS) include short stature secondary to growth hormone insufficiency, excessive appetite (hyperphagia) and mild learning disabilities. Affected children characteristically live in conditions of high psychosocial stress. Symptoms resolve when the child is removed from the stressful environment. Family studies indicate a genetic predisposition. Aims: To compare the behavioural and stress profiles of HSS with those of Prader-Willi syndrome (PWS), and to test the hypothesis that the genetic locus that predisposes to HSS co-inherits with the PWS locus at 15q11-13. Method: Twenty-five children with HSS, mean age 9.1 (s.d. 3.8) years, 28% female, were compared with 30 children with PWS, mean age 8.8 (s.d 2.8)years, 33% female. Results: The clinical profiles were largely similar across the conditions, but no evidence was found in HSS of co-inheritance of the PWS critical region. Conclusions: Hyperphagic short stature is one of the very few behavioural diseases associated with a pathognomonic physiological abnormality. Investigations of the suggested genetic dysregulation, which is so sensitive to environmental influences, may well be of importance in a broader context.