Classical psychological twin studies have yielded in part equivocal and sometimes contradictory results. Besides the complexity of the problem, the delicate character of the diagnosis, and the rudimentary tools which were used, several other factors are underlying this situation: (1) insufficient systematization of the set-up and the careless design of the investigations; (2) lack of follow-up studies; (3) uncertain diagnosis of zygosity; in MZ twins no attention to the age of the ovum at the time of cleavage; (4) lack of consideration for antenatal and perinatal influences; (5) no attention to the typical circumstances linked to the twin situation. All this makes it difficult to balance nature against nurture on the basis of comparison between MZ twins, DZ twins, and singletons. Interactions may also appear between the effect of twinning and other factors such as the socioeconomic circumstances. A new investigation was therefore started where, besides the twins, a group of matched control singletons was constituted. The follow-up study is now completed up to the age of 5 years in 13 MZ and 20 DZ twin pairs (+ controls, that is to say, 99 children).

The children were observed and subjected to psychological tests at the age of 6 months and of 1, 2, 3, 4, and 5 years.

Three sources of observation relevant to the measurement of individual differences in emotional and esthetic expressiveness were employed to study their heritability by application to a sample of some 60 pairs of young adult like-sexed twins, approximately evenly divided between male and female and MZ and DZ pairs. The sources of observation were objective test performances, trait ascription using a standard list of adjectives, and videotaped enactments of mood and esthetic performances. Perceptual and esthetic abilities do appear to have substantial heritability, although esthetic preferences do not. Heritability is also indicated for such adjectives as artistic, inventive, original, and independent. Ratings of the videotape performances yielded somewhat ambiguous results, due to the presence of a marked halo effect; the most likely interpretation congruent with earlier results is that greater MZ twin resemblances in social extroversion generated greater resemblances in the videotape situation on such other trait-rating variables as creativity, naturalness, and dominance.

A sample of 27 MZ and 32 DZ twin pairs, aged 6 to 12 years, has been tested with the Draw A Family Test. Significantly higher concordance values in MZ than DZ twins have been found with respect to some graphic-structural factors (i.e.: line, hand pressure, area of the drawing, dimensions of the figures, distribution, and shading) as well as with respect to contents factors, such as spatial representation and cotwin's valorization. These correlates of personality development would thus appear to undergo significant genetic conditioning.

As part of the National Heart and Lung Institute multicenter study of twins, 190 twin pairs (93 MZ, 97 DZ) residing in California and aged 44-55 years were comprehensively studied for all risk factors for coronary heart disease and for Behavior Pattern Type A or B. Psychological tests included MMPI, CPI, 16 Cattell PF, Cough Adjective Check List (ACL), Thurstone Temperament Schedule (TTS). Heritability at statistically significant levels was found only for scales of TTS. Twelve scales of ACL and five scales of TTS showed significant correlations with Behavior Pattern Type A-B as well as with several risk factors, including blood pressure and serum lipids. Multiple regression equations were constructed for those characteristics accounting for significant and unique portions of the total variance of Type A-B Behavior. The use of certain scales of ACL and TTS may provide a new questionnaire for screening purposes in the assessment of Behavior Pattern Type A-B.

Further advances in research into the etiology of schizophrenia will depend on the identification of an unambigous indicator of the genotype associated with the development of schizophrenia. Such an indicator would permit accurate assessment of the relatives of probands as “affected” or not, so that the data generated in twin and family studies could be tested for the best fit to various genetic models that have been proposed. Schizoidia or schizoid personality has been considered by clinicians to be such an indicator, but it has been beset by semantic and logical difficulties. Most troublesome has been the extent to which the concept implies (merely) a phenotypic resemblance to schizophrenia, or a genotypie connection with it, or both. Four different but overlapping meanings for the concept of schizoidia are presented, in an effort to clarify the semantic and logic involved. Following Popper's notions about the testability and refutability of theories, the authors, identified with both monogenic and polygenic theories, apply the definitions to their first-hand observations of the cotwins in the Maudsley-Bethlem Schizophrenic Twin Study. Pushing the concept to its limit, 91 % of 22 MZ pairs and 45% of 33 DZ pairs contained “disordered” cotwins.

Phychoanalytic diagnostic methods and measures have been applied to 50 neurotic twins belonging to 21 MZ and to 16 same-sex and 13 opposite-sex DZ pairs. The 100 subjects consist of 64 adults and 36 children or adolescents. All 100 subjects were personally seen and psychologically examined. The mean intrapair difference of all MZ twin pairs amounts to 3.81 scaling points in a scored degree of severity of the neurosis; that of all DZ pairs to 5.00 points. The distribution of 657 neurotic symptoms in a chi-square table of the 21 MZ and 29 DZ twin pairs shows that 32.7% of the symptons are concordant in the MZ sample, but only 16.7% in the DZ sample. Hereditary influence could be shown in the manifestation of neurotic depressive symptoms, maladaptive oral and aggressive behavior, as well as in schizoid behavior deviations. Hereditary factors play a role in the formation of the neurotic character structure.

Regarding the environmental pathogenic factors, subjects more heavily stressed in early childhood were found, on the whole, more severely neurotic in later life.

A genealogical analysis is carried out on the pedigrees of 10 twin pairs with two or more psychoses. The probands' symptoms reveal some peculiar aspects, i.e., an atypical phenomenology possibly due to the interference of more pathological genes. Schizophrenia, depression, epilepsy, and obsessive neurosis, are found in the pedigrees in different combinations. The study of these pedigrees would lead to the conclusion that interaction of more than one psychosis gives rise to atypical forms as a result of an attempt to establish a state of balance between opposing dynamic actions, as in reversible chemical reactions. Probands' symptoms are less severe and with an often more favourable prognosis. Epilepsy tends to become independent and the major psychoses seem to be epistatic on it. Af for obsessive-compulsive neurosis, probands may progress into schizophrenia or depression if one of these psychoses is present n the pedigree, or may represent the neurotic form of the major disease.

Departures from the usual human brain asymmetry, manifested in unusual laterality of motor dominance and/or speech representation, seem to have some genetic basis, and have been found associated with: schizophrenia, epilepsy, alcoholism, dyslexia, dysphasia, autism, and mental retardation. This can also derive from embryonic disturbances, as evidenced by excessive association with: first births, late births, birth difficulties, and twinning. MZ twins develop from embryos which have often split after at least some commitments to the cellular development of bilateral symmetry have been made. The effects of such a split are visibly recorded in mirror-imaging, in tooth emergence patterns, in shapes of mouth, nostrils, eyes, and ears, in hairwhorl placement and pattern. Brainfunction laterality is also found to be subject to mirror-imaging.

Data from the 1972 publication of the Gottesman and Shields genetic twin study of schizophrenia serve to illustrate the power of the neglected embryonic discriminator: Fully one-third of their MZ schizophrenic sample {nearly ten times the best population estimate) were characterized as lefthanded or ambidextrous. If the sample is divided between pairs with and without any sign of laterality disturbance, the results are very strikingly altered. The pairs with no sign of laterality disturbance are 88% concordant, whereas unusual laterality pairs are 24% concordant. Several severity indicators are in excess, by ratios of 2 to 10-fold, among the RH pairs. Nuclear subtypes are (2.5) times as frequent, and schizoid premorbid personalities are twice as frequent, among the RH pairs.

It is the aim of twin studies to obtain results which are not only valid for twins, but apply to the whole population. Therefore the following questions have to be answered first: do twins differ from non-twins in the trait under study? Do different nongenetic factors act upon MZ and DZ twins which alter the probability of manifestation of a trait, even before birth? There are important differences in embryogenesis and placental blood flow in mono- and dichorionic twins; this can influence the normal fetal development. Therefore the value of twin studies alone in analysing the genetic component in the etiology of congenital malformations is rather ambiguous. Twin studies beyond the newborn period can be classified into four approaches: (1) Case reports; (2) Accumulated case reports; (3) Limited representative sample; (4) Unlimited representative sample. The most frequent systematic method in medical genetics is the establishment of all twins in a defined population of probands (3). Another successful application in the last few years has been in pharmacogenetics. Although no simple mode of inheritance could be discovered, it was possible to estimate the genetic component within the interindividual variability of the metabolism of certain drugs (nortriptyline, antipyrine, phenylbutazone, ethanol). Now, additional non-twin research is needed to work out single factors within the observed polygenic systems.

The purpose of this review is to bring out the clinical value of a twin pair, when a disease strikes one or both partners. A “Clinical Cotwin Method” is thus described.

In the case of concordant disease in MZ twins, the points of interest suggested by this method are the study of (1) the etiopathogenesis of the disease; (2) the genetic variability in the manifestation of such disease; (3) the variability of expression of the morbid genotype; and (4) the chronogenetic variability, that is, the possible difference between times of onset of disease, of its symptoms, and of its outcome. In the case of discordant disease in MZ twins, either one twin is ill and the other healthy, or else, twins have two different diseases. In the first case, the clinician finds an excellent basis of comparison in the healthy twin, which allows him to extend his knowledge of the morbid phenotype and to discover minimal symptoms which would otherwise go unobserved. In the case of two different diseases which strike MZ twins simultaneously, comparative analysis of the general symptoms is possible, which allows a deeper knowledge of the etiopathogenesis of the morbid processes. DZ twins also are of high scientific interest because their semiequivalent genotypes have simultaneous times of departure. This situation differs from that of full sibs and that of half sibs; it is also very useful to analyze the disease that DZ twins face in the same physical time. Both twin care and scientific research can be greatly helped by hospital department of twins, as well as outpatient departments or consultants for occasional and routine visits.

A case of MZ twins, both affected by Wolf's syndrome, is described. Their mother, of subnormal look and low intellectual level is translocated. The children, born with a weight and size much below the average, show a very special morphotype: a hook-nose, an abnormal conformation of the back edge of the nostrils (a protrusion in the shape of a horn overhanging the filtrum), hypertelorism, microcephaly. Great asynchronism in the maturation of the bones and a somatoschisis of the body of the cervical vertebrae are noted. Deletion of the short arm chromosome 4 is juxtacentromeric. The study of blood and tissue groups corroborates monozygosity. Dermatoglyphs are little abnormal and identical in the two children. The mother's family is phenotypically normal. At 19 months of age, measuring is still below 4, psychomotor progress is extremely weak, and convulsions are frequent.

From January 1971 to March 1973 all twin pairs in the Swedish Twin Registry below the age of 70, who became death-discordant, were continuously recorded. A total of 205 (78%) of the surviving cotwins were examined with respect to different manifestations of ischemic heart diseases (IHD) and several “environmental” and “biometric” risk factors. Among the death-discordant pairs, the cause of death was IHD in 57 pairs and other than IHD in 148 pairs. Analyses revealed that the prevalence rate of myocardial infarction, angina pectoris, pathologic Q-wave, and ST depressions in connection with exercise, were significantly higher among the surviving cotwins whose partners had died from IHD than those whose partners had died from other causes. The same trends were seen for most of the risk factors measured both singly and in combination, although not very pronounced. The results indicate a substantial genetic influence in the development of IHD. The genetic influence is possibly transmitted not only through some of the risk factors measured, but also through other factors, still unknown.

In an investigation in 1967 of about 100 male twin pairs collected from the Swedish Twin Register, discordance with respect to the presence of CHD was found in 37 pairs of which 19 were MZ. The investigation included physical examination, cholesterol measurements, and an interview regarding, among other things, smoking habits. In a follow-up study in 1974 — seven years after the original investigation — all but one of the 37 twins regarded in 1967 as free from overt CHD could be traced. Ten of the 36 twins had developed symptoms of overt CHD (angina pectoris or infarction); 18 twins were still healthy, 2 had died from other causes, and 6 had questionable complaints of breast pains. In a comparison of the two groups of twins with and without symptoms of overt CHD, no differences were found with respect to blood pressure, serum cholesterol, or smoking habits, as presented at the 1967 investigation. It is concluded that none of these factors seemed to influence the future development of CHD in twins apparently tainted with a heredity for this disease.

An intravenous and oral glucose tolerance test and an intravenous tolbutamide test have been performed in 11 MZ twin pairs, discordant for diabetes mellitus. Blood sugar, immunoreactive insulin, and free fatty acids were determined. The research aimed at finding out whether prediabetic subjects may show any characteristic parameter which could be suggestive of the hereditary disposition. Three MZ twins of juvenile diabetics showed a normal blood glucose, immunoreactive insulin, and free fatty acids during the glucose and tolbutamide loads within a maximum of 10 years observation.

A clinical and genetic study on 25 twin pairs with at least one deaf member was performed. Concordance rate of hearing loss was 0.88 in MZ and 0.50 in DZ pairs, with an almost complete penetrance (P = 0.94). Consanguinity was found in 32% of cases, corresponding to five times the average population rate in Japan.

A school population has been screened to locate same-sexed twins with myopia and also to compare intelligence test performance of myopic and nonmyopic individuals. Augmentation of the twin data by a survey of the world literature has led to the identification of a total of 106 MZ twin pairs, 100 of them concordant for myopia, as well as 41 DZ pairs, 12 concordant. Myopic students score eight points higher on IQ tests than nonmyopes, the entire bell shaped distribution curve being shifted to a higher range. The intellectual gain precedes in time the development of nearsightedness.

An oculistic and orthoptic screening has been carried out on a sample of 122 twins aged 6 to 10 years (31 MZ male and 30 MZ female pairs). A few remarks could be made, concerning both twins as such and the heritability of the traits under examination. The twins appear to differ from the general population of singletons of the same age on account of a lower frequency of ametropia and strabismus as well as of a high frequency of epicanthus.

Fetal risk in twin pregnancy is recognized as being about 2 to 4 times higher than in singletons. The main factors of this increased mortality are reviewed. Pathological effects associated with MZ origin are mainly due to the “third circulation” occurring in monochorial twins. Three situations can be distinguished: (a) hemodynamic equilibrium resulting in fetal growth impairment, (b) strong hemodynamic imbalance inducing fetal death, (c) moderate imbalance as the cause of “intertwin transfusion syndrome”. The acardiac and to some extent the papyraceus fetus can be considered as particular cases of the same problem. Other risks associated with MZ twins are the higher rate of malformations and umbilical cord entanglement in monoamniotic twins. The conjoined effects of prematurity and intrauterine growth retardation are undoubtedly the main cause of fetal death in multiple births. Therefore, some consideration is given to the underlying physiopathogenic factors. Prevention of twin weight defects demands early diagnosis of multiple pregnancy. As little can be expected from classical clinical methods, the obstetrician has to rely on more sophisticated techniques such as fetal ultrasonography. Even with an early diagnosis, at the present time there is no satisfactory treatment capable of preventing prematurity and retarded fetal growth. In this specific context, bed rest would appear as a fallacy.

In 1972 the rate of multiple births showed a much more substantial decrease than in the years before. In the period 1963-1971 it dropped from 20.3‰ to 19.3‰ and in 1972 to 18.3‰. The frequency of low birth weight in children from a multiple birth is 10 times higher than in all newborn children and the early neonatal mortality of children from a multiple birth is 8 times higher than that of all newborn infants. Cerebral damage is 30 times higher in children of low birth weight than in children of normal birth weight. In the period 1965-1967 perinatal death associated with cerebral damage (recorded on the death certificate) accounted for 5.7% of all children of low birth weight and for 0.2% of children weighing at birth over 2500 g. Eearly diagnosis of multiple pregnancy and early in-patient care of women with multiple pregnancy will improve the development of multiple fetuses and give children from a multiple birth much better chances in life. In all twin studies it has to be considered that a relatively high proportion of twins is affected to a higher or lesser degree by cerebral damage.

Multiple pregnancies reach full term only in a remarkably lower percentage with respect to single pregnancies. Even in the case of multiparae, delivery occurs some three weeks before term. Complications may concern either pregnancy and Puerperium or delivery. The former include (1) abortions, especially frequent in the case of monoplacental and monochorialpregnancies; (2) rarer events, such as hydramnios, placenta praevia, association of an ectopic pregnancy with an intrauterine pregnancy, molar degeneration of one egg with normal development of the other; (3) gestoses of the first and second trimester, more frequent than in single pregnancy; and (4) higher incidence, during Puerperium, of hemorrhage, phlebitis, and uterine subinvolution. With respect to delivery, normal delivery only occurs in approximately 70% of twin pregnancies, the period of dilatation being generally longer than normal. Better assistance and techniques during labor and especially in the interval between delivery of first and second twin have remarkably reduced the higher mortality rate, especially for the second twin.