Annual serial records in the form of facial contour maps were examined for 18 like-sexed twin pairs of near equal zygosity distribution. Zygosity diagnosis was based primarily on hematological reports for 26 of the 36 children and the remainder were diagnosed on a basis of the concordance or discordance of various physical characteristics: standing height, finger print ridge count, tooth size, and hair and eye colour. Thirteen facial parameters were measured on 274 maps. After age correcting and theree-point smoothing, more than 1,150 intrapair differences of individual facial parameters were measured. In general, the dizygotic twin pairs had the larger mean intrapair differences in facial parameters and the monozygotic twin pairs had the smaller intrapair mean differences. The more important facial parameters for distinguishing the two groups were identified and used to calculate a “facial similarity index”.

Among 520 sibships, in which at least one child was an epileptic and for which the family history and clinical findings were quite complete, there were 294 with one parent affected, 222 with neither parent, and 4 with both parents affected. Numerical tests on the pooled data show quite definitely that epilepsy is inherited as if due to a simple autosomal dominant gene with approximately 65% penetrance. Since about 65% of all epilepsy is genetic and since there is about 65 penetrance in genetic epilepsy, the 2 factors effectively balance one another, so that the incidence of epilepsy in the population, 1 in 200, may be taken as the frequency of individuals with a genetic constitution for epilepsy.

Assuming random mating, the gene frequency for the dominant gene for epilepsy is 0.0025 and for the normal recessive allele the value is 0.9975. It follows that only about 1 in 160,000 is homozygous for the dominant gene for epilepsy and that 99.5% of the population are genetically normal. For the genetic counselor it is of interest that if one parent has a genetic constitution for epilepsy the frequency among the children is about 36%, and if one child in such a family has epilepsy the empirical probability of another child having epilepsy is about in 1 in 8, which having regard to the standard error, agrees with the degree of concordance (10.3±1.8%) in dizygotic twins, as should be expected.

In a patient the authors observed the following association of anomalies: bilateral hydrophthalmos with microcornea pseudo-plana, a thick-set somatic pattern, a small lower yaw, arterial hypertension, diabetes, disseminated intracranial calcifications, electro-encephalographic disturbances and neurological pseudo-extrapyramidal lesion.

His brother shows the following association of anomalies: unilateral hydraphthalmos, a thick-set somatic pattern, a small lower jaw, arterial hypertension, diabetes, digitiform impressions on the RX of the skull and neurological pseudo-extrapyramidal lesions.

The mother and grandmother of these two patients both showed a trembling of head and limbs, even as diabetes; by this means a dominant and polyphenic hereditary transmission must be accepted.

The Danish Twin Register, which comprises all twins born in Denmark between 1870 and 1920, has been used for studies of selected problems in the field of epidemiology and public health. This report gives a survey of the preliminary results of an investigation of this type, which intends to amplify the present knowledge about the possible harmful effects of smoking on health, by taking advantage of a twin material which makes it possible to keep the genetic factors under control.

A series of 762 MZ and same-sexed DZ twin pairs, which had their smoking habits mapped in 1959, has been followed continuously, and the mortality which has occurred in this group has been analysed in relation to tobacco consumption. Neither MZ nor DZ pairs showed any tendency to increased mortality in the heavier smoking cotwins. When the material was subdivided according to cause of death, no conspicuous exception from the general pattern was found, but the subgroups were relatively small.

The distribution of selected diseases and symptoms, mainly of the cardiovascular and respiratory systems, was studied in this and a second series, followed since 1966, with a total of 1584 pairs.

A high heritability estimate was obtained for serum arylesterase activity level in a series of 40 male twin pairs (23 MZ, 17 DZ) aged 33–39 years. The heritability estimated for Cholinesterase activity was strikingly lower. In unrelated individuals a positive correlation between arylesterase, Cholinesterase, and various lipoprotein parameters appeared to support the suggestion that these enzymes interact with various lipoproteins at the molecular level. The nature of these associations is not known. It is, however, tempting to speculate that some of the hereditary influence on lipoprotein levels in man may be mediated through the genetic control of one or both of these enzymes.

Interindividual variation in odor identification and olfactory sensitivity has been explained primarily with reference to age, sex and/or experiential factors. A twin study of olfaction can, therefore, substantially contribute to current research in this area. Thirty-nine monozygotic and twenty dizygotic twin pairs have completed the University of Pennsylvania Smell Identification Test (UPSIT), an olfactory preference questionnaire, and two odor detection threshold tests (phenyl ethyl alcohol and butanol). A genetic influence on odor identification, as assessed by the UPSIT, has been demonstrated. Future plans and directions for this research program are discussed.

The authors report on six patients exhibiting a congenital heart disease and malformations of the upper limbs. In two of them this association is similar to that described by Holt and Oram in 1960: atrial septal defect, heart arrythmia and abnormal thumbs. The other four patients have the same skeletal anomalies but different heart malformations. Dermatoglyphic studies revealed a high frequency of a distal position of the axial triradius and of an equivalent of a simian crease. The karyotypes are all normal. The etiology is discussed.

Early diagnosis and subsequent management of twin pregnancy resulted in a considerable reduction of preterm deliveries (26% vs 61% for late diagnoses).

A continuous series of 483 twin deliveries was studied. In 30% of cases, intravenous oxytocic treatment was given for labour induction or to accelerate the first stage. In 13% of twin deliveries this treatment was applied only after the first twin's birth. In the group perfused during cervix dilatation, foetal mortality rate was significantly lower than in the nontreated group. In order to understand the reason(s) for this difference, the following factors were studied in relation to oxytocic treatment: parity, obstetrical complications, second stage duration, abnormal presentations, obstetrical maneuvers, and birth weight. Contrasting with mortality data, Apgar scores of first twins were significantly lower in the oxytocin-treated group. In summary, several variables indirectly linked to oxytocic treatment could have favoured or hampered foetal outcome in the treated group. Therefore, it is difficult to ascertain if the use of oxytocics is helpful in twin pregnancy management. In the majority of cases, however, it may at least be considered harmless.

In order to examine the chronological changes in genetic variance and heritability of arterial systolic and diastolic blood pressure (SBP and DBP) of Chinese infants in Taiwan, a total of 339 same-sexed twin neonates born in four major general teaching hospitals in Taipei City were studied. Based on placentation and 12 red blood cell antigens, 274 monozygotic (MZ) and 65 dizygotic (DZ) twin pairs were identified and followed up to the age of one year. Both SBP and DBP were measured by Doppler blood pressure monitor. Within-pair mean squares of SBP and DBP were consistently smaller in MZ than DZ twins at ages one month and over. The findings remained unchanged after the adjustment for the effects of age, sex, gestational age, placentation and physical state during blood pressure measurement. Falconer's heritability indices for adjusted SBP and DBP at ages two months and over ranged from 0.29 to 0.55 and from 0.27 to 0.45, respectively. The study indicates an important genetic influence on blood pressure during infancy.

Neither the percentage in the previous use of contraceptive pills nor the distribution of the time interval between the discontinuation of the pill and conception has shown any significant difference in twins and control singletons. Twin conception within one month after discontinuation of the norethynodrel type pill, however, was significantly more frequent, whereas after the use of the linestrenol type, it was lower.

A case of trisomy E with phocomelia of one arm is presented and the hitherto reported cases of trisomy E with phocomelia are listed. The different causes of phocomelia are discussed. Similarities and dissimilarities of the clinical picture of conditions associated with phocomelia are presented.

Inheritance patterns of digital ridge counts have been analyzed using multivariate statistical methods and data from the offspring of half-sib twin kinships. Prior studies found the univariate measure total ridge count to be highly heritable and the counts on individual fingers to be somewhat less heritable, and exploratory factor analytic studies indicated that at least two, and possibly three, independent genetic influences are responsible for this ten variable multivariate trait.

Two statistical methods have been employed to elucidate the factors controlling ridge count development on all ten fingers. An exploratory method developed by Bock and Vandenberg [4] has been applied to the among and between mean square matrices from a multivariate nested analysis of variance on thirty balanced male twin kinships. A principal component analysis on the resulting matrix of pure genetic effects has revealed two substantial genetic factors. One strongly influences the counts on all ten fingers, with the largest loadings on the three central fingers of each hand, while the other has an impact on the thumbs and fifth fingers. For both factors the loadings on homologous fingers are nearly equal. This exploratory procedure is wasteful of the data that is available in half-sib twin kinships, however.

Confirmatory factor analyses, employing the LISREL IV program, have been conducted on all available ridge count data from the offspring of forty-eight unbalanced male twin kinships and fiftynine unbalanced female twin kinships. Nested analyses of variance performed on sex-adjusted data yielded five 10 × 10 variance-covariance matrices containing 275 unique statistics for the estimation of genetic and environmental parameters and the testing of hypotheses.

A series of ten genetic and environmental hypothetical models for ridge count development, each more complex than the previous one, have been tested. They include a simple environmental model, an additive genetic and environmental model proposed by Holt [16], a full additive genetic model including five separate finger factors, two laterality factors and a general genetic factor, and seven models augmenting this full additive genetic model with factors for maternal epistatic and general environmental effects. The most complete model, which includes eight additive (one general, two laterality, and five finger) as well as maternal, epistatic, and general environmental factors cannot be rejected at a .05 level of significance. This model accounts for 99% of the variance that cannot be accounted for by a simple environmental model, and 95% of the variance unaccounted for by Holt's model. It suggests that while a strong genetic factor influences the ridge counts on all ten fingers, there are other factors affecting the counts on the homologous fingers separately as well as different factors affecting the counts on the left and right hands. In addition to these additive effects, influences due to the maternal environment common to all pregnancies of the mother, and those due to the unique environment of each pregnancy of the mother, and those due to the interaction of genes at separate loci have also been detected.

Results of the Bock and Vandenberg analysis are concordant with those obtained by the LISREL program. While the former only requires the availability of standard statistical packages, it is wasteful of data from the half-sib families. The latter, on the other hand, while it requires the use of a specific program, LISREL or its equivalent, uses all half-sibship data and allows one to test genetic and environmental hypotheses as well as conduct exploratory factor analyses.

Present attempts to identify genes contributing to coronary heart disease (CHD) risk focus on “candidate genes”. With respect to CHD this could be any gene whose protein product is directly or indirectly involved in atherogenesis, thrombogenesis or thrombolysis/fibrinolysis. Genes that exhibit associations with absolute risk factor levels may be referred to as “level genes” to distinguish them from “variability genes”, which are genes involved in establishing the framework within which environmental influences may cause risk factor variation. In a series of persons recruited from the Norwegian Twin Panel, confirmatory evidence for level gene effect with respect to apolipoprotein B (apoB) concentration was found with an XbaI polymorphism in DNA at the apoB locus corresponding to residue 2,488 in the mature protein. Evidence for variability gene effect with respect to apoB as well as body mass index emerged with DNA variants in the 3′ part of the apoB gene. Level gene effect with respect to apolipoprotein A-I (apoA-I) and high density lipoprotein (HDL) cholesterol as well as apparent variability gene effect with respect to total and LDL cholesterol were detected with a DNA polymorphism at the cholesteryl ester transfer protein (CETP) locus. The first example of interaction between normal genes in determining risk factor level was uncovered in analysis of the apolipoprotein E (apoE) polymorphism and a restriction fragment length polymorphism (RFLP) at the low density lipoprotein receptor (LDLR) locus. An LDLR gene identified by presence of a PvuII restriction site eliminated completely the well known effect of the apoE4 allele on cholesterol level. Finally, in families where high Lp(a) lipoprotein level (a well established risk factor for CHD) segregated as a Mendelian trait, very close linkage with an RFLP at the plasminogen locus was established and DNA variation at the LPA locus reflecting varying numbers of a structure homologous to the “kringle IV” region of plasminogen was uncovered.

Data are presented from a large-scale population-based study in Northern Ireland, in which multiple sources of ascertainment were used. As found in other studies, the overall prevalence at birth of congenital anomalies amogst twins (285.4/10,000) was somewhat higher than the rate amongst singletons (241.8/10,000). Unlike in other studies, however, the rate amongst twins of like sex (287.8/10,000) was not markedly higher than that amongst twins of unlike sex (252.3/10,000). Problems of comparison between series are discussed.

A large kindred (4 generations) with pseudo-pseudo-hypoparathyroidism (PPHP) and the clinical, biological and anthropometric features of this syndrome are extensively described.

The association of PPHP with diabetes, hypertension, hypothyroidism, polyarthrosis and peripheral arteritis is very probably significant.

Gonadal dysgenesis with brachymetacarpy must clearly be distinguished from PPHP.

The transmission of PPHP is probably not sex-linked dominant but autosomal dominant with an incomplete penetrance of about 50%, a varying expressivity and weak familial specificity. Partial sex limiting or sex predominance may occur, instead of true sex-linkage in this condition.

The effect of ionizing radiation, from a 100 Curie Cobalt-60 source, on diploid human cells grown in vitro has been investigated.

The analysed cell populations originated from foetal brain and lung tissue. Other known variations of this material were age and sex of the foetuses, primary and first transfer cultures.

The effect was measured by recording post-metaphase chromosomal aberrations in cell cultures fixed and stained 24 and 48 hours after acute irradiation. “Spontaneous” aberration frequencies were determined in matched control cultures.

Although conclusions must be guarded, in view of the insufficient knowledge of factors influencing human cell populations in vitro, our observations can be summarized, tentatively, in the following main points.

1. The frequency of “spontaneous” aberrations appears to vary with respect to (a) differences between the individuals from whom the biopsies were taken, (b) tissue of origin whether within or between individuals and (c) the sex of the cultured cells.

The qualified estimates of the overall averages of “spontaneous” aberrations were, (a) for the cell cultures derived from foetal lung 0.7 per cent (41/5,891 scored cells) and (b) for the cell cultures derived from foetal brain 2.5 per cent (21/851 scored cells).

2. In the irradiated cell cultures which received doses varying from 9-136 rads of absorbed dose the number of aberrant post-metaphases per 100 cells per rad varied from 0.10-0.15 for cultures derived from lung tissue and from 0.19-0.37 for cultures derived from brain tissue, all at 24 hours after the acute dose. At 48 hours after irradiation the frequencies were somewhat lower but the same trends remained.

3. The cell cultures derived from brain tissue appear to have a higher radio-sensitivity than those derived from lung tissue. Furthermore, a sexual dimorphism is suggested because, in all series of cultures, those composed of XY cells had a higher aberration frequency as compared to those with XX cells.

4. The irradiation doubling dose (for definition, see p. 27) was estimated at 15-40 rads (cf. table 7).

The complex serologic behavior of the Rh-Hr agglutinogens has been underlined by the recent discovery that, with very rare exceptions, associated with blood factor Rh0 of Rh-positive blood, there are numerous other blood factors which we designated RhA, RhB, RhC. Rare Rh-positive individuals exist whose bloods have blood factor Rh0 but lack one or more of the other components. Such individuals can and have become sensitized to the missing blood factor. For example, in the case of an Rh-positive individual lacking blood factor RhA, anti-RhA may be produced. So, too, when RhB and RhC, are lacking, anti-RhB or anti-RhC may be produced. In fact, all 3 have been identified. The resulting anti-RhA, anti-RhB and anti-RhC serums are indistinguishable from “standard” anti-Rh0 serum in parallel tests on a random series of blood specimens, unless the series happens to include one of the rare Rh-positive bloods lacking blood factor RhA (type Rh0a or type Rh1a, etc.).

In the present paper, anti-RhA serum from a sensitized type Rh1a mother whose child had erythroblastosis was used for studies on the distribution and heredity of the RhA blood factor. In addition, attention is called to the fact that Unger and Wiener have identified anti-RhB and anti-RhC although they are reporting at this time their studies with anti-RhA. A total of 2012 blood specimens from Rh0-positive individuals were tested; 951 from Caucasoids and 918 from Negroids. In tests on blood from Caucasoids, a “standard” Rh0 blood factor was invariably associated with a “standard” RhA blood factor. In no instance where the reactions with anti-Rh0 serums were typical was the RhA factor absent or a variant. However, if the Rh0 factor was a variant, 3 possibilities with regard to factor RhA were identified. Either factor RhA was “standard”, or factor RhA was a variant, or factor RhA was absent. This last possibility rarely occurs in Caucasoids since in our series only 1 Caucasoid blood or 0.1 percent lacked RhA blood factor and in that case the Rh0 factor was a variant.

Among the 918 Rh-positive blood specimens from Negroids examined the situation was found to be somewhat different. While a “standard” Rh0, was almost always associated with a “standard” RhA, in 0.9 percent the RhA factor was absent. Among bloods with a Rh0 variant blood factor, just as with Caucasoids, all 3 possibilities were identified, namely bloods with “standard” RhA, with RhA variant, and also bloods with blood factor RhA absent. The incidence of Rh-positive bloods lacking factor RhA was considerably higher among Negroids than among Caucasoids, namely, 1.6 percent in Negroids, as compared with only 0.1 percent in Caucasoids.

One interesting family was studied. The father's blood had the “standard” Rh0 blood factor, but lacked the RhA component (type Rh0a). The mother's blood had the Rh0 variant blood factor, and also lacked blood factor RhA (type ). The child's blood was of the same type as its mother, namely, Rh0 variant and lacking blood factor RhA (type ). The possible genetic explanations for these observations and their clinical significance were discussed.

Nation-wide data in Japan on births and prenatal deaths of 16 sets of quintuplets during 1974-1985 were analysed. Among the 16 sets, 3 sets were liveborn, 8 were stillborn, and 5 were mixed, with a stillbirth rate of 0.64 (51/80). Effects of sex, maternal age and birth order on the stillbirth rate were not considered because of the small sample size. Effects of gestational age and birthweight on stillbirth rate were also examined. The mean weight of the 40 quintuplet individuals was 1,048 g.