Aetiology of idiopathic growth hormone deficiency in England and Wales

Information on height, sex, age, and condition of mothers' pregnancy and labour was obtained on all first- and second-degree relatives of 140 cases of idiopathic growth hormone deficiency (GHD). Less detailed information was available for 68 further cases, the two samples together constituting all cases from England and Wales treated under the Medical Research Council Clinical Trial of Human Growth Hormone up till 1974. Compared with the Perinatal Mortality survey of 1958, idiopathic GHD cases showed a significantly greater incidence of breech births (13-7%), of forceps deliveries especially in multiparae (5-6%), and of reported early vaginal bleeding (7-1%). The incidences of breech and forceps were both higher in cases with multiple pituitary hormone deficiency than in cases of 'isolated' GHD. The frequency of either breech or forceps was 43% in multiple and 20% in 'isolated' GHD. Heights of fathers and sibs of affected cases averaged the 50th centile; those of mothers the 35th centile. The ratio of boys to girls affected was 3-8. There were 4 families with more than one member affected; 4-5% of the brothers of probands were themselves affected, 2% of fathers and 1-5% of both sisters and mothers. In the world literature the sex ratio averages about 2-9 with little difference between series; the frequency of breech delivery averages 21% with large differences (2% to 50%) between series. A table of relative risks is given from which a screening procedure may be constructed; following 1% of selected births would give 10% of cases, and 20% of births 50% of cases. We propose a multifactorial aetiology for GHD which brings it into line with malformations such as anencephaly, cleft lip and palate, and pyloric stenosis. An underlying liability to the disease is postulated, continuously distributed in the population and depending on both polygenic and environmental factors among which sex and birth trauma are important. The disease becomes manifest when the liability value reaches a fixed threshold. On this assumption, heritability of idopathic GHD is approximately the same as that of coeliac disease, pyloric stenosis, and patent ductus.