Biomedical subjects
Publications and source records attributed to N C Myrianthopoulos.
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.
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. The group of individuals with NTD was compared to a group of 400 randomly selected non-malformed control infants. Of over 50 maternal factors studied the following showed significant association with NTD in the offspring: diabetes mellitus; organic heart disease; lung disease; and diuretic, antihistamine, and sulfonamide use. The interval between the termination of the immediately previous pregnancy and the start of the proband pregnancy was significantly shorter in mothers of NTD children than in mothers of control infants. The risk for NTD was also significantly increased if the immediately previous pregnancy was a spontaneous abortion. There was no increased risk for NTDs among sibs of children with major malformations such as tracheo-esophageal "dysraphism," cleft lip/palate, or renal agenesis. NTDs are apparently etiologically heterogeneous.
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 2.5 weeks younger than normal controls, though birthweight was normal for gestational age. Nearly 1/3 of the liveborn infants with AN died within 15 minutes, 2/3 within 3 hours; 3 AN infants survived to 48 hours. Details and discussions of the pathologic findings and their physiologic significance are presented. Regarding those AN infants who received detailed neurologic examinations, correlations are made between the brain pathology and neurologic function prior to death.
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. In general, the highest degree of burden was observed in syndromes and sequences, followed by multiple and single major anomalies. The burden due to major abnormalities as measured by attributable risk ranged from 0.436 for prolonged hospitalization up to one year, to 0.010 for chronic infections in subjects 1-7 years of age. In terms of mortality, the total attributable risk was 0.164, and the mean potential years of life lost was 5,020 per 10,000 population, which is considerably greater than that reported in other studies. An index constructed from mortality, neurologic, psychologic, and surgical variables provides a reasonable and objective means for classifying anomalies into severe and mild types.
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.
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). Multiple variable adjustment for potentially confounding factors further reduced the risk ratios. Caesarean section did not appear to be a risk factor in this population, but further studies covering more recent times and including fetal deaths are needed.
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. The frequencies of the remaining dermatoglyphic traits showed no significant differences. We conclude that none of the marker systems tested show a particular pattern of association in patients and controls or a genetic predisposition to either disorder, and that early identification of at-risk individuals remains elusive.
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.
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. Generally, the data were consistent with increased risk of malignant neoplasms among children of women exposed to X-rays before and during pregnancy, with a somewhat higher relative risk estimate for preconception exposure. No significant association of X-ray exposure and benign neoplasms was detected.
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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. Dichorionic MZ twins had a significantly greater within-pair variation than monochorionic MZ twins for total ridge count. In summary, then, these data could offer little support to prior speculation that monochorial placenta may present less favorable environments for feta development.
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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. Significant genetic variability for diastolic blood pressure (DBP) was found in the twins, with a heritability estimate of 0.53. Systolic blood pressure (SBP) results tended in the same direction but were not statistically significant. The trends were comparable for both sexes and races. These findings suggest that even at a young age substantial genetic influences on DBP variability are detectable.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.