Ntinos C. Myrianthopoulos

The relation of ethnic and selected socio‐economic factors to human birth‐weight*

Among the biological variables which characterize the newborn, birth-weight occupies a unique position : it is universally present, has a continuous distribution and can be measured accurately. Birth-weight is an important indicator of the survival and future growth of the newborn. It is not surprising therefore that it has been extensively studied, especially from the obstetric and pediatric viewpoints, and that its relationships with other variables are being constantly investigated and reappraised. Investigations of the relative influences of various genetic and environmental factors on birthweight have shown that although foetal genetic constitution, including sex, is responsible for a large part of birth-weight variation, the most important component depends on maternal factors, both genetic and environmental (Donald, 1939; Karn & Penrose, 1951; Karn, LangBrown, MacKenzie & Penrose, 1951; Penrose, 1954a, b ; Morton, 1955). Veryfew attempts have been made to investigate the relations of socio-economic factors to birth-weight. Racial differences in birth-weight are also well recognized. In the United States non-White babies (mostly Negro) weigh on the average 50 g. less than White babies (U.S. Dept. H.E.W., 1954), but as Gruenwald (1964) correctly points out, the role of racial factors is undetermined as long as one cannot compare races a t the same socio-economic level. The racial differences in birth-weight have not been sufficiently studied to determine if genetic factors of some magnitude are involved in their occurrence. It is the purpose of the study reported here to assess the contribution of a number of selected socio-economic factors to the variation of human birth-weight and the role which racial differences may play in such variation.

Intellectual Development of Twins — Comparison with Singletons

Analysis of mental and motor tests scores and intelligence test performance of twins born in the Collaborative Perinatal Project shows that twins perform more poorly than singletons from the same population and that the differences are greater in Negroes than in whites. The poor performance of twins relative to that of singletons is of complex etiology. It is partly due to poor prenatal environment, for twins brought up as singletons perform at the intelligence level of twins and not of singletons. It may also be partly due to the higher incidence of congenital malformations in twins, especially those of the central nervous system. But the performance of twins, relative to that of singletons, tends to improve as they get older, at least from 4 to 7 years, suggesting that prematurity is also a contributing factor, whose detrimental effects may be reversible.

Intellectual Development of Children from Interracial Matings

Interracial offspring of white mothers obtained significantly higher IQ scores at 4 years of age than interracial offspring of Negro mothers, suggesting that environmental factors play an important role in the lower intellectual performance of Negro children.

Intellectual Development of Children from Interracial Matings: Performance in Infancy and at 4 Years

Psychological tests at 8 months and at 4 years of age were administered to 129 children of interracial (Negro-white) matings in the Collaborative Study. These interracial children were divided into two groups, depending on whether the mother was the white or the Negro partner. Stanford-Binet IQs of the 4-year-old children of white mothers averaged approximately 9 points higher than those with Negro mothers (p<0.01). The only behavioral difference on the Bayley Scales of Infant Development at 8 months of age was in favor of the interracial children of Negro mothers (p<0.05). The results are interpreted as supporting the hypothesis that postnatal environmental factors make a very substantial contribution to racial differences in intelligence test performance.

Population Dynamics of Tay-Sachs Disease. II. What Confers the Selective Advantage Upon the Jewish Heterozygote?

It is now well established that the birth incidence of Tay-Sachs disease (TSD) is a hundred times higher, and the gene frequency ten times higher among Ashkenazi Jews than among other Jewish groups and non-Jewish populations (Goldschmidt et al., 1956, Kozinn et al., 1957, Myrianthopoulos, 1962, Aronson, 1964). The present authors (Myrianthopoulos and Aronson, 1966) examined several possible mechanisms but found no evidence that differential breeding pattern, genetic drift or differential mutation rate could explain the difference in gene frequency distribution. We then tested the possibility of differential fertility of the heterozygote for the TSD gene by comparing the reproductive performance of the grandparents of a large number of Jewish infants affected with TSD with that of an appropriate control group. The results suggested that the Jewish TSD heterozygote enjoys an overall reproductive advantage of about 6% over the presumed Jewish homozygous normal and that TSD sibships had significantly higher survival to age 21 than did control sibships. This advantage is of more than sufficient magnitude to have raised the frequency of the lethal TSD gene among the Ashkenazi Jews from a presumed frequency equal to that of non-Jews of 0.0013 at the end of the first century A.D. when the mass emigration of the Jews began, through 50 generations to the late 19th century, when TSD was recognized as occurring chiefly among Ashkenazi Jews with a gene frequency of 0.0126.

A survey of twins in the population of a prospective collaborative study.

This report is concerned with the twin births which occurred in the Collaborative Study of Cerebral Palsy, Mental Retardation and Other Neurological and Sensory Disorders of Infancy and Childhood. This is a collaborative endeavor of 14 institutions throughout the US and the National Institute of Neurological Diseases and Stroke, to observe and study factors which affect the parents before a child is born and to relate them to the outcome of pregnancy. To this end, we are following approximately 60 000 pregnant women from the first months of their pregnancy, through labor and delivery and up to the seventh year of the study childs life. The Study population is about 46% White, 46% Negro, 7% Puerto Rican, and the rest a variety of other ethnic groups. The prospective nature of the study makes possible the recording of observations with high accuracy and the avoidance of biases inherent in other types of investigations. These advantages should also be reflected in the collection and evaluation of twin data.

Estimates of Genetic Variance for Anterior Fontanelle Development in the NCPP Twin Population

There are several dynamic influences on anterior fontanelle development in infants; among them, brain growth, dural attachments, suture development, and osteogenesis, It thus seems reasonable to hypothesize that variation in anterior fontanelle development between infants, related and unrelated, might have a significant genetic component. Anterior fontanelle size was quantitated by the method of Popich and Smith for 94 monozygotic (MZ) and 187 dizygotic (DZ) four-month-old twin pairs. The general model for estimating genetic variance from quantitative twin data was applied to MZ and DZ twins and then separately by chorion type. Since there were significant mean differences between blacks and whites, races were analyzed separately. The within-pair mean square estimates of genetic variance (GWT) were highly significant for both blacks (less than 0.02) and whites (P less than 0.002). Comparisons of means, total variances, and among-pair mean squares within races revealed no heterogeneity. There were also no significant chorion effects. Since the anterior fontanelle closes at around 1--1 1/2 years of age, it was evaluated at age one in 95 MZ and 194 DZ twin pairs as a qualitative trait - ie, open vs closed, concordance vs discordance. There were no significant differences in proband concordance rates between MZ and DZ twin pairs for either blacks (P greater than 0.5) or whites (P greater than 0.10). Again, there were no significant chorion effects. These data suggest that anterior fontanelle developmental variation has a significant genetic variance component at four months of age but not at one year. This finding may be related to the rapid brain growth witnessed between birth and eight to nine months of age.

A case of conjoined twins.

Among 56,249 maternities in the Collaborative Perinatal Project, 615 were twin maternities. One of these resulted in stillborn thoracoomphalopagus MZ female twins with multiple cardiovascular, alimentary and other malformations. The case is of further interest in that the mother had a surgically removed brain tumor in childhood and exhibited neurological symptoms and bizarre behavior before and during pregnancy. Drugs and treatments which she received during pregnancy are not known to be teratogenic.

Molecular Approaches in the Prenatal Diagnosis and Therapy of Genetic Disorders

During the last decade a new class of DNA markers, the restriction fragment length polymorphisms (RFLPs), has been developed by molecular genetic techniques. Genetic linkage studies using RFLPs have resulted in a large number of chromosome assignments of genes, making possible prenatal diagnosis and presymptomatic testing in many genetic disorders. Even so, of the estimated 100,000 genes that comprise the human genome fewer than 2,000, or 2%, have been mapped. Studies of the molecular basis of some of these mutant genes have brought to light a remarkable multiplicity and diversity of mutations that produce relatively few clinical phenotypes. Many genetic disorders including the thalassemias, familial hypercholesterolemia, Tay-Sachs disease, cystic fibrosis, and congenital adrenal hyperplasia, have been shown to be genetically heterogeneous. It is necessary, therefore, to know the precise mutation in order to make accurate diagnosis and restore proper enzyme or gene function.