Spina Bifida and Anencephalus in Greater London

Abstract

Summary. In order to make comparisons with the findings in a high frequency area, South Wales, with those in a low frequency area, south-east England, a birth frequency and family study was made of all births with neural tube malformations (spina bifida cystica, encephalocele, anencephaly, and iniencephaly) in 32 of the 33 London Boroughs over a 3-year period from 1 April 1965 to 31 March 1968. The births were ascertained through local authority registers, stillbirth and infant death certificates, and hospital records. The frequencies found were 1-54 for spina bifida (including encephalocele) and 1 41 for anencephaly (including iniencephaly). This was less than four tenths of the South Wales frequency. Evidence of an excess of winter births was found for both types of malformation, with a peak for conceptions in February, March, and April.The parents of 870 of the original 1209 index patients were traced and visited for the family survey. The usual social class effect was seen, a deficit of fathers in social class I and II. The birth order distribution of legitimately born patients standardized for maternal age showed only a small excess of firstborn and a deficit rather than an excess of lateborn. For maternal age, however, standardized for birth order, there was an excess of patients born to mothers under 20 and over 35 years of age. The whole family study sample showed a striking excess of patients born to parents from India and Pakistan compared to parents born in the West Indies in relation to households of immigrant parents in the 1966 sample Census. A small sample of 164 patients with matched controls had more parents born in Ireland and India and Pakistan and fewer born in south-east England and the West Indies than the controls.The proportions ofsibs affected with spina bifida and anencephaly were 3 42% for spina bifida index patients and 5 44% for anencephaly. For patients born after the index patient the proportions were 5-17 and 4-17%, respectively. The overall risk to sibs was lower than that shown in the South Wales survey, but substantially higher relative to the population birth frequency. The risk to sibs was not apparently influenced by father's social class but there was an indication of an effect of mother's father's social class, with a lower risk where mother had grown up in a class I, II, or IIIa home. There was no apparent influence of grandparental birth place. There was no apparent effect ofa relative affected other than a sib. Among cousins a significant increase over the population birth frequency was seen only in mother's sisters' children. The findings, like those of earlier surveys, suggest a multifactorial aetiology of the neural tube malformations, depending both on genetic predisposition and environmental triggers.

Some further observations on parental consanguineous marriages of anencephaly in Japan

“…However, these high consanguineous marriages were especially obtained from Alexandria and Bombay. On the other hand, a rate of parental cousin marriage for the malformations in South Wales and Greater London was low, but higher than that estimated for the corresponding general population (Carter et al, 1968;Carter and Evans, 1973).…”

Congenital malformations and other disorders: the influence of genetic and nongenetic factors. Final report, January 1, 1974--June 30, 1975. [US populations]

“…In Great Britain, the risk of spina bifida cystica in sibs born subsequently to propositi with this disorder is over 5% (Carter and Evans, 1973). Even though only 107 families were included in this study in Utah, and therefore the reliability of the estimates may be questioned, the frequency of sibs with spina bifida cystica is of the order of magnitude expected if the genetic predisposition has a polygenic mode of inheritance.…”

“…The authors estimate that not more than 50 per cent of the total cases had been located, and cases of dysplasia Numerous studies have been carried out during the past decade to determine if spina bifida cystica has a genetic component (Williamson, 1965;Carter, David, and Laurence, 1968;Richards, Mcintosh, and Sweenine, 1972;Carter and Evans, 1973)» The results of these studies indicate the complexity of the situation.…”

“…Renwick (1972) presents the intriguing hypothesis that an unidentified substance in certain potato tubers is a major teratogenic agent. Carter and Evans (1973) obtained heritability estimates of 0. 60, 0.…”

“…Both malformations are increased in frequency in the sibs of propositi with either disorder. Based on their own studies and data found in the literature, Carter and Evans (1973) suggest that both of these malformations of the central nervous system are influenced by a genetic predisposition depending on variation at several loci and additional environmental factors. Renwick (1972) presents the intriguing hypothesis that an unidentified substance in certain potato tubers is a major teratogenic agent.…”