New hereditary malformation syndrome of unusual facial appearance, skeletal deformities, and musculoskeletal and sensory defects.

We report on a new syndrome characterized by specific and striking facial abnormalities, arthrogrypotic skeletal deformities, and neuromuscular and sensory defects in a large Greek Cypriot family. The hereditary transmission appears to be autosomal dominant with quite variable expressivity.

Congenital anomalies: mortality and morbidity, burden and classification.

This study has attempted to assess the burden imposed by congenital anomalies in terms of postnatal mortality and morbidity, which were in turn used to classify anomalies as severe and mild types. Factors studied were postnatal mortality through age 7 years and morbidity, as measured by neurologic and psychologic abnormalities, histories of major surgery, prolonged hospitalization, and chronic infections. The study was based on a prospective study of 52,332 liveborn singletons of the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke.

Studies in neural tube defects. II. Pathologic findings in a prospectively collected series of anencephalics.

This report presents the pathologic anatomy of a prospectively collected series of 36 anencephalic infants. This series provides an opportunity to investigate the epidemiology of organ system pathology in anencephaly (AN) as well as other facets of its natural history. AN infants had a mean gestational age 2.

Studies in neural tube defects. I. Epidemiologic and etiologic aspects.

In the NIH Collaborative Perinatal Project, a prospective study of over 53,000 pregnant women and their offspring, 71 single-born children (13.33/10,000) were found to have a non-syndromal neural tube defect (NTD). A family history was present in only one case.

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.

Caesarean section as a risk factor for malformations--a negative finding.

The question whether Caesarean section is a risk factor for malformations was examined among 35,865 children born in 1959-65 and included in the US Collaborative Perinatal Project; 1,407 children were subsequent children of mothers who had a Caesarean section for the previous birth (exposed). The rate of malformed children was about the same in the exposed and non-exposed groups, and the rate of children with major malformations was only slightly higher in the exposed group (risk ratio was 1.1, ie not statistically significant).

Blood groups, immunoglobulin allotypes and dermatoglyphic features of patients with amyotrophic lateral sclerosis and parkinsonism-dementia of Guam.

Blood group frequencies, immunoglobulin allotypes, and dermatoglyphic patterns were determined on patients with amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PD), two chronic, degenerative, neurologic disorders of unknown cause found commonly among the Chamorros of the Mariana Islands, in an attempt to identify a specific genetic or phenetic marker associated with either disorder. With the exception of the Kidd system, no significant differences were found in blood group frequencies nor in immunoglobulin allotypes between ALS patients, PD patients, and unaffected controls. The dermatoglyphic analysis demonstrated that ALS patients had higher frequencies of palmar patterns and accessory triradii in the IV interdigital area, and PD patients had significantly higher frequencies of complete simian creases and of palmar patterns in the thenar/I interdigital area than unaffected controls.

Preconception radiation, intrauterine diagnostic radiation, and childhood neoplasia.

Diagnostic X-ray examinations as a potential risk for neoplasia were investigated in a prospective study of 55,908 women who participated in the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke. The X-ray exposure histories of 145 mothers whose children developed neoplasms and 290 matched controls were examined. Of the childhood neoplasms, 40 were malignant and 105 were benign.

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.

Detection of genetic variance in blood pressure of seven-year-old twins.

Results from twin studies in older children and adults indicate that there is significant genetic variance for blood pressure (BP). Utilizing date which were collected in 12 US university-affiliated hospitals in 1966-1973 in the Collaborative Perinatal Project (NCPP), the authors sought to determine if the effects of heredity on BP variability are apparent in younger twins. BP was determined in 197 pairs of like-sexed twins at seven years of age.

The effects of chorion type on normal and abnormal developmental variation in monozygous twins.

To determine the effects, if any, of chorion type on normal and abnormal developmental variation in monozygous (MZ) twins, we tested the hypothesis that disparate environments that are related to chorion type have no effect on this variation. The parameters studied included congenital anomalies and dermatoglyphics (total ridge count and right-left asymmetry). With the exception of total ridge count, analyses of these data failed to reject the null hypothesis.

The effects of chorion type on variation in IQ in the NCPP twin population.

The 7-year IQ scores (WISC) of 116 white and 143 black nonmalformed twins of known zygosity and placental type were ascertained from the NINCDS Collaborative Perinatal Project (NCPP). The type of chorion and zygosity had no significant effect on the mean IQ or among-pair variation. In white monozygotic twins, however, analysis of variance revealed a significantly greater within-pair mean square for dichorionic twins than monochorionic twins.

Risks to the offspring of women treated with hydantoin anticonvulsants, with emphasis on the fetal hydantoin syndrome.

The fetal hydantoin syndrome is a variable pattern of altered growth and performance which includes unusual facies, distal phalangeal hyoplasia, and other defects occurring in some infants exposed in utero to hydantoins. A prospective study of 35 infants exposed prenatally to this class of anticonvulsants showed that 11% had sufficient features to be classified as having the fetal hydantoin syndrome. An additional 31% displayed some features compatible with the prenatal effects of hydantoins.

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.