A review of the literature on twin studies in craniofacial genetics is presented. The following areas are particularly dealt with: tooth form and size, tooth formation and eruption, dental arch and occlusion, facial form and size, and cleft lip and palate.

The predictive relationship between neonatal behavior and temperament at 6 months was assessed in 62 pairs of twins. The neonatal assessment evaluated irritability, resistance to soothing, reactivity, and activity level across various activities. Temperament at 6 months was appraised by a laboratory assessment, ratings on the Infant Behavior Record, and a questionnaire completed by the mother. Examination for temperament consistency from the neonatal period to 6 months indicated that (a) neonates rated by an examiner as irritable and difficult to soothe were reported by the mother to be more negative, irritable, and slower to adapt at 6 months; (b) neonates rated as more irritable and active were more attentive and responsive during mental testing at 6 months; (c) there was no relationship between the neonatal measures and the laboratory ratings, possibly reflecting methodological problems influenced by maturation and vegetative processes at 6 months. Analyses for patterns of concordance within the various data sets for MZ and DZ twins indicated that there was no pattern of differential concordance favoring MZ twins for the temperament measures at birth or at 6 months. It was concluded that a modest predictive relationship between temperament variables had been demonstrated from birth to 6 months, but no specific genetic effects were detected at these early ages.

In the NAS-NRC Registry, all major diseases are more common in DZ than in MZ twins. Furthermore, concordance rates for most disorders are lower in the registry than would be expected. In this article we propose a general model which seeks to explain these phenomena. The model explores the impact of traits which increase or decrease the probability of enrollment of individuals given that the registry, like the NAS-NRC, includes only pairs where both members are enrolled. If the trait decreases the probability of selection into the registry, both the prevalence of and concordance for the trait in the registry will be lower than that found in the population. A trait which increases the probability of selection has the opposite effects. However, the magnitude of these effects are a function of the population concordance. If population concordance differs in MZ and DZ twins, the effect of differential enrollment will not be the same for the two zygosity groups. The article examines the impact of differential enrollment on estimates of heritability and common environment and explores ways in which estimates of prevalence and concordance rates can be obtained which are free of the bias introduced by selection.

For 98 pairs of MZ twins, four measures indicating degree of cotwin closeness were correlated with absolute differences between IQ scores within pairs. In two different twin samples (40 MZ vs 40 DZ pairs and 169 MZ vs 174 DZ pairs, respectively), means and standard deviations in the closeness variables were obtained for MZ and DZ pairs. Whereas MZ cotwins were clearly closer than DZ cotwins, the relation between cotwin closeness and similarity in IQ seemed rather weak and ambiguous. “Years lived together in childhood home” were positively related to similarity in IQ (P < 0.01), whereas subjective feeling of closeness in contact tended to be negatively related to similarity in IQ.

The number of AgNOR (NOR+) and the amount of AgNOR (NORM+) were analysed by means of two multilevel analyses of variance in a total of 12 twin pairs: 3 female and 4 male MZ and 5 male DZ pairs. In the first analysis, only zygosity was controlled; in the second, chromosome types D and G were controlled as well as the interaction between chromosome type and zygosity. For NOR+ and NORM+, when chromosome types D and G are not distinguished, the within-pair variance is greater, though not significantly, in DZ than in MZ pairs; but it is highly significantly greater when chromosome type (D or G type) is under control. This confirms an important genetic determination of NOR+ and NORM+ when in the ANOVA model the D and G types are controlled. However, nongenetic factors also influence the Ag-NOR patterns, but not enough to conceal the genetically defined rDNA pattern. Indeed, about 50% of the cells transcribe their rDNA in a way not closely dependent on the rDNA background and significant intrapair differences of NOR+ pattern exist in MZ twins.

In order to study the influence of heredity on resting metabolic rate (RMR), 20 monozygotic and 19 dizygotic male twin pairs aged 20.6 (SD 2.9) and 21.4 (SD 3.1) years, gave their consent to participate in the experiment. Fat free weight (FFW) was estimated from underwater weighing. RMR was measured by indirect calorimetry using an open circuit system. RMR was expressed as kJ · min−1, kJ/m2 · h−1, kJ/kg · h−1 and kJ/kgFFW · h−1. Significant intraclass coefficients were observed in MZ twins for the different expressions of RMR. The values ranged from r = 0.45 (P < 0.05) to r = 0.81 (P < 0.01). However, DZ twins demonstrated lower intraclass coefficients for RMR, with a range from r = 0.21 to r = 0.44. Significant (P < 0.05) DZ resemblance was revealed only when RMR was expressed as kJ · min−1 and kJ/kg · h−1. Results of the present study suggest that variations in RMR may have a genetic component. Implications for human energy balance and body fat are discussed.

Genetic and environmental influences on the phenotypic expressions of several biological markers were studied in 18 monozygous (MZ) and 8 dizygous (DZ)twin pairs. Zygosity was determined using ABO, Rh, and HLA. The biomarkers studied included: T & B lymphocytes, suppressor and helper T lymphocytes (Tγ, Tμ), T cell (PHA) mitogen activation (MA), serum immunoglobulins (IgA, IgM, and IgG), plasma carcinoembryonic antigen (CEA), aryl-hydrocarbon hydroxylase (AHH) and sister chromatid exchange (SCE) in lymphocytes. Temporal variation of markers over a 6-month period was not significant. The mean absolute differences between levels from first and second blood draws were less than one standard deviation. Variability associated with age was not significant. Females had higher levels of T lymphocytes than males. A gender related association was observed for the IgM immunoglobulin test: females had a higher mean level of IgM. Smoking was found to influence the levels of SCE, T helper lymphocytes and mitogen activation. The variability of these biomarkers within and between twin pairs was quantified. Immunoglobulin levels, particularly that of IgM, showed statistically greater similarity within MZ twins than within DZ twins. Several other markers suggested heritability.

When the Weinberg estimate of the proportion of monozygotic pairs is quite deviant from that in the source population, it is likely to be wrong because Weinberg's difference is much less stable than the zygosity proportions. A formula is proposed for the probability distribution of possible compositions of a small sample of twins based on sex concordance in the sample and zygosity proportions in the source population.

From 1971 to 1981, 16752 women were delivered at the University Women's Clinic in Heidelberg; 228 of these were twin pregnancies (1.36%). The relationships between sex, gestational age, birthweight, mortality, and fetal outcome were investigated. For the reason of grading, so-called χ2 curves are used. These curves show the strength and the course of relationship between two parameters. Mortality of the twin (8.3%) depended on birthweight and on sex of the infant, but not on the mode of delivery. All twins were ‘small-for-date’ (25th weight percentile of single births). Starting at the 35th week of gestation, the increase in weight decelerated additionally. So, immaturity as well as twin-related factors led to the high mortality rate for twins. Fetal outcome was evaluated in respect to the birthweight and to the delivery interval.

Reference intervals for human placental lactogen (hPL) and dU-estrogens (dU-E) in uncomplicated twin pregnancies are found to be higher than singleton pregnancies and considerably wider. Significantly more monozygotic than dizygotic pregnancies, and significantly more monoplacental than diplacental pregnancies showed hPL values below the median on the normal range curve. The same was not found for dU-E. Significantly more growth-retarded fetuses were found in monoplacental than diplacental pregnancies. The benefit of measuring the two parameters in order to identify the intrauterine growth retarded fetuses were evaluated in terms of sensitivity and specificity. Both parameters were found less suitable for the purpose.

In 33 out of 51 women studied in late gestation, the uterus was found to phasically compress the pelvic vessels and impede the venous blood flow during quiet standing. This caused a reduction of the cardiac stroke volume with resultant reduction of systemic blood pressure and a compensatory increased heart rate (range of increases 9-51 beats/min). In all cases uterine contractions (mostly subclinical) coincided with the phase of circulatory readjustment. Apparently, the contracting uterus, by changing its position and/or shape, relieves the venous obstruction and prevents decompensation. In the women displaying the uterine compression syndrome (UCS), uterine activity was markedly increased in standing compared to the left recumbent position.

It was also investigated whether the UCS appeared more often and earlier in gestation in women with twins. In all 9 women with twin pregnancies (mean gestational age 28 5/7 weeks) the UCS associated with uterine contractions was apparent in the standing posture. Although at present no definite conclusions can be reached on the effect on the cervix of these contractions, quiet standing especially in twin pregnancies seems to provoke an increased uterine activity and should therefore be avoided.

Acute polyhydramnios in the second trimestr is a typical complication in monozygous twin pregnancies. It is caused by a feto-fetal transfusion with anemia on the donor and polycytemia on the recipient twin. Contrary to the chronic hydramnios, there is no increase in malformations. In view of the high mortality rate (100%, according to most authors), the clinical management has to be reconsidered. During the years 1979 to 1983, 10 cases of acute polyhydramnios have been observed at the University Hospital in Zurich. This corresponds to an incidence of 9% in our twin population. All cases investigated were MZ twin pregnancies. With the exception of one patient, who underwent an abortion, all women were hospitalized, had bed rest and received recurrent removals of amniotic fluid and prophylactic tocolysis. The mean gestational age at the time of diagnosis was 23 4/7 weeks and at delivery 30 3/7 weeks. In two cases – one of which is presented in detail – with an unintentional puncture of a placental vessel, the recurrence of the hydramnios did not appear. Eight of 18 newborns survived. No malformations were found. Bed rest, tocolysis and recurrent amniocenteses seem to have a positive influence on the prolongation and outcome of the gestation in acute polyhydramnios.

A total of 146 twin pregnancies were studied to evaluate the importance of bed rest. A significantly reduced frequency of preterm delivery was found after bed rest in hospital as compared to bed rest at home or no bed rest at all. An increase in gestational age and in birth weight was seen after bed rest. No effect was found on the intrauterine increase of fetal weight per time. Early routine ultrasound is recommended, so that effective bed rest may be instituted in due time.

Factors presumed to influence intrauterine growth were analyzed among 192 twin pairs. Mean birthweight was considerably reduced compared to single pregnancies, and a high proportion of twins were growth retarded (12.4%). One fifth of the twin pairs presented an intrapair birthweight difference exceeding 20%. DZ twins were sligthly heavier than the MZ, while dichorionic twins had a somewhat higher birthweight than the monochorionic. The intrapair weight differences were greater in twins with fused dichorionic placentae than in those with separate ones. The umbilical cord insertion seemed to influence intrauterine growth. Fetuses with velamentously or marginally inserted cords presented more frequently retarded growth than twins with centrally inserted umbilical cords. Though a total of 13 cases of twin transfusion syndromes were observed, these were not characterized by great intrapair weight differences.

Monozygotic twins with typical trisomy 13 are reported. Despite an identical karyotype, the twins were dimorphic for the presence of an omphalocele. Reasons for the rarity of MZ twins with trisomy 13 are presented. It is suggested that the presence of a chromosomal abnormality in MZ twins may predispose to dimorphism.

Triplet pregnancy of over 20 weeks gestation occurred 20 times during 75,506 deliveries at a referral hospital. Commonly occurring maternal complications included premature delivery (75%), antepartum anemia (35%), postpartum hemorrhage (35%), preeclampsia (20%), and premature spontaneous rupture of the membranes (20%). Malpresentation was common. Neonatal complications were also common and included respiratory distress syndrome (45%), presumptive sepsis (36.6%), hyperbilirubinemia (33%), and neonatal death (21.6%). These high complication rates emphasize the importance of early identification and referral center care for these vulnerable pregnancies.

During the years 1979-1980, a prospective study was carried out to evaluate the value and efficacy of routine hospital bed rest in the prevention of premature birth and pregnancy complications in twin gestation. This was done by comparing hospital bed rest to special antenatal care at outpatient clinic. Since the results did not support the idea of using routine hospital bed rest, this was abandoned. Because the material was rather small, the results of the changed policy of management were controlled in the present follow-up study. The material consists of 102 twin pregnancies diagnosed during the years 1982-1983. The number of deliveries before the 34th gestational week and of < 1500 g weighing infants were still decreasing (9.0% and 3.0%). Perinatal mortality after the 24th gestational week was 2.0%. The follow-up study confirmed the unefficacy of routine hospital bed rest. Early diagnosis is the basis of the management of twin pregnancy. This allows counselling of the pregnant women, regular examinations to detect pregnancy complications, and also planning of the delivery.

An analysis of all perinatal deaths occurring in twin pregnancies in Dundee women from 1956 to 1983 was performed. The uncorrected perinatal mortality rate fell from 116/1000 births in 1956-60 to 16/1000 births in 1981-83, this fall almost entirely taking place after 1975. Causes of death were identified using the Aberdeen Classification and a reduction in deaths in all cause groupings occurred. About half of the deaths were in the Premature, Cause Unknown group and a marked decrease in deaths in this group made the largest contribution to the improved perinatal mortality rate. This fall was partly due to a reduction in the incidence of extreme prematurity and low birth weight. Changes in obstetric management which may have influenced outcome included the introduction of routine early pregnancy ultrasound scanning, the use of tocolytic drugs, intrapartum fetal monitoring, epidural analgesia and an increase in Caesarean section rate from 2% in 1956-60 to 39% in 1981-83.

The authors describe a pair of twins, one of whom showed acardia while the other had severe neural tube defect including anencephaly. This is the first observation of a fetal malformation (anencephaly) in the cotwin of an acardius and confirms the fact that even the cotwin of an acardiac fetus may be at risk of severe congenital malformations.