Energy and protein intake as measured by 24-hour urinary nitrogen values are similar in twin and singleton pregnancies. The relationship between urinary nitrogen and nitrogen intake is equally significant in twin and singleton pregnancies. Dietary zinc, copper, and iron are not different in women with twins, nor are the levels of these elements in plasma. These observations are surprising in view of the extra fetal demands on the mother and the different adaptation of twin pregnancies.

Many chronological correlations in different plant and animal species, in populations, in human families, and between cotwins, prove the existence of characteristic biological times. Some such times also tend to be related to cosmic time, in which they develop and from which they are induced, resulting in peculiar composite times, such as the daily, monthly, or annual rhythms, that are the object of study of chronobiology.

Beyond these examples of exogenous chronological induction, the existence of a hereditary biological time is postulated, as the basic phenomenon in the relationship between time and life. The newborn scientific branch of chronogenetics is devoted to the study of the fundamental, endogenous genetic time, with its theoretical and practical, normal and pathologic implications. To explain and interpret the mechanisms of the hereditary biological time, the authors have developed a model based on the concepts of ergon (i.e., stability of the gene) and chronon (i.e., lifespan of the information). This Ergon/Chronon System is related to the gene, bringing into focus the fourth dimension and the dynamic aspects of the unit of inheritance.

The applications of chronogenetics extend to every expression of life, from the most primitive unicellular to the higher plants and animals. In the area of normal human traits, the study of the hereditary biological time contributes significantly to the interpretation of such phenomena as development, reproduction, homeostasis, and senescence. In the area of medicine, chronogenetics interpretes, unifies, and develops the temporal phenomena of inheritance. In a future perspective, chronogenetics appears to be fundamental for eugenics, preventive medicine, and prognosis.

Volunteer adult twins (aged 18-65), after a 12-hour fast, provide two 15 ml samples of blood for analysis by Auto Analyzer II, by agarose electrophoresis and by direct gas chromatography. Provisional diagnosis of zygosity is based on subjects' own opinions, supported by dermatoglyphic analysis and, in any difficult case, substantiated by an enzymatic series. Analysis of the AA-II and electrophoresis data on the first 2 × 45 subjects shows a significant positive correlation within MZ pairs for each of the 7 lipid measurements considered, while the estimate of correlation within DZ pairs is lower in every case. Heritability appears to be higher for cholesterol than for triglyceride fractions. The electrophoretic band for the sinking pre-beta lipoprotein fractions has behaved like a simple genetic marker. Interrelationships among different lipoprotein fractions are studied in terms both of phenotypic and genetic correlations, both of which confirm the expected positive association between amounts of triglyceride and of cholesterol in the supernatant (Sf > 20), and both also show negative correlation between the pre-beta and the alpha fractions. Another aspect of the analysis is the study of lipid differences between MZ cotwins in relation to corresponding intrapair differences in body weight and medical history; male, but not female pairs, show a measurable statistical dependence of cholesterol and triglyceride levels on « excess » body weight.

The simultaneous occurrence of sarcoidosis in two 24yearold white men who where enzygotic twins is reported. Manifestations of the disease as well as its clinical course were identical in both twins.

Continuous wave Doppler ultrasound was used to study the twin fetus in 76 multiple pregnancies. The technique is not difficult and allowed the identification of the small for gestional age twin in both intrauterine growth failure and twin to twin transfusion syndrome.

This study included two groups of 37 children, one of twins and the other singletons at 4 years of age. All subjects had birthweights under 1500 grams and individuals in the groups were matched for birth date, gender and birthweight. Except when parental socio-economic status was taken into account, no significant differences between twins and singletons were observed on any of the results of The Stanford-Binet Intelligence Scale, nor were there any when the twins and singletons were divided into groups with birthweights < 1000 grams and 1000 to 1499 grams. When cognitive scores were analysed in relation to socio-economic status, there were significant differences in the whole population between subjects in the high and low socioeconomic status groups, with higher mean scores for the former. Comparison of the twins and singletons with parents in the lower socio-economic status group did not produce any significant differences but in the case of the upper socio-economic status group the singletons scored significantly better that the twins in Quantitative Reasoning and on the Composite Score. No significant differences were demonstrated in the clinical assessment of speech, language or behaviour. So far as general life considerations and health were concerned only one significant difference was found and this was for the number of siblings born subsequently, with more born in the singleton families. This study did not provide support for the view that singletons and twins differ significantly in the areas considered.

The frequency of a hereditary abnormality of erythocytes characterised by a deficiency in glucose 6 phosphate dehydrogenase and glutathione instability, has been investigated in various population groups in Israel. The highest frequencies of this abnormality have been detected among Jews from Kurdistan, Iraq and Persia. It is also relatively common in other oriental (sefardic) Jewish communities, as well as among Arabs, desert Bedouins and Druses.

Up to now only one case of this erythrocyte defect has been found among Jews of Ashkenazic origin. The same abnormality has also been found in a Sikh from Punjab.

The hereditary pattern of transmission and evidences of sex linkage are presented. The problem of expressivity of the abnormal gene in heterozygous females is discussed.

The frequency of triplets in the U.S. white population may have reached an all-time low around 1964, at 78 sets per million deliveries. One-fourth of those were monozygotic as estimated by the difference method, or 18% by Bulmer's theoretical model. By 1983 the frequency of triplets had nearly doubled, the increase presumably occurring in dizygotic and trizygotic types. In Belgium most triplet pregnancies now result from artificial induction of ovulation, which is expected to occur mainly in older mothers. In the U.S., however, triplets have increased as much in young mothers as in older mothers, proportionally. This age distribution of the increase may be partly explained by a decrease in parity in older mothers since 1964.

The twinning phenomenon has always interested the great public, the artists, and naturally the scientists. Isidore Geoffroy St. Hilaire has established a classification still now valid. This classification considers the different types of double monsters which are found in nature in all classes of vertebrates, including man. To explain the twinning phenomenon, the experimental realizations have progressed by successive bounds after the preliminary attempts of different authors. Now, when it is question of experimental duplication, anybody thinks of Speman for the amphibians, of Lutz for the birds, of Seidel for the rabbit, and of Tarkowsky for the mouse. Now, it is possible to conceive a twinning resulting from the separation of the first blastomeres (amphibian, rabbit, mouse) and a twinning originating from the fissuration of the blastoderm (bird, mammal). All these experiments confirm the unicist-theory. If a total or partial regulation of the excedents may be experimentally realized, no argument can however support this theory in the realization of the double monstrosity.

Kinships composed of twin parents, their spouses and children, offer a robust and flexible sampling design for research in genetic epidemiology. Families-of-twins designs circumvent some of the sampling problems that arise when independent data sets are combined, and these designs provide unique evaluations of maternal influences, assortative mating and X-linkage. Unfortunately, empirical studies of families of twin parents have been limited by relatively small samples and by the self-selection biases intrinsic in ascertainment of families from volunteer twin registries.

A large and representative cohort of monozygotic and dizygotic twin parents, drawn from a population-based twin registry, provides the optimal sampling frame for twin-family research. This paper reviews the sampling considerations underlying the initial family study based on the Finnish Twin Cohort and evaluates the representativeness of the sampled twins. Spouses and adult children (over 18 years) of 236 pairs of twins, about equally divided by gender and zygosity, were evaluated by a postal questionnaire. Individual response rates exceeded 86% and in 464 of the 472 nuclear families (98.3% ), at last one member of the twin's family completed the questionnaire. The sampled twins, selected for fecundity to maximize statistical power of the obtained data, were broadly representative of non-selected twins drawn from the Cohort, with whom they were matched on age, gender, and zygosity. Such results suggest that the Finnish Cohort has excellent potential for extended twin-family research designs.

May I begin by recalling that at the Copenhagen Conference five years ago, Tjio and Levan had just published their almost apologetic announcement that they could only find 46 chromosomes in cultured human somatic cells, and Hamerton and I presented evidence that there were 23 bivalents in spermatocytes, not 24.

Since that time there has been a very marked expansion of work in human cytogenetics. The reason is not hard to seek: the findings have been of significance in so many fields of medicine ranging from endocrinology, through paediatrics, gynaecology and mental diseases to haematology and cancer.

To the biologist, this outpouring of interest may seem at times to have bordered on the hysterical. For him the developments may have done little more than illustrate in our own species the principles that were established in the twenties and thirties with other material. On second throughts he will realize that man offers unique advantages for cytogenetic study in virtue of the enormous numbers of individuals who are subjected to medical scrutiny and thereby become candidates for chromosomal examination. But he will also remember the serious disadvantages, (some shared with human Mendelian genetics) of long generation time, small family size, impossibility of experimental mating and lack of opportunity (except perhaps rarely in males) to study the meiotic pairing which can be so revealing of homology.

If opportunities for direct test of an interpretation are few, reliance on general hypotheses must be the greater. I make it a rule to doubt an observation if it is not in accord with hypothesis. This is not to reject Bateson's exhortation to “treasure your exceptions”; but one must first make quite sure that they are exceptions. Perhaps one does not make so many new discoveries this way, but fewer may later be shown not to be discoveries after all.

A questionnaire was given to parents of twins concerning their perceptions of dependency and similarity in their twin children. Also, the parents were asked if they tried to influence their children to become more dissimilar. 70 samesex twin pairs (35 MZ and 35 DZ) were included in the study and a questionnaire was sent both to the mother and the father of the twins. The twins were approximately 12 years old and attended grade 4, 5 or 6 in the Swedish compulsory school. Results indicated that parents consider MZ twins to be dependent upon each other and to spend more time together. This was especially evident for girls. If the twins had a free choice they would also tend to choose similarly. This trend was also more pronounced for the MZ girls. Irrespective of zygosity, most parents reported that they did not try to influence their children. In the case of MZ twins this will probably make them become more similar over time. Differences between maternal and paternal answers tended to be nonsignificant.

Six skinfold measurements, and percent body fat and fat-free weight derived from the underwater weighing technique were obtained in 43 pairs of male and 44 pairs of female monozygotic (MZ) twins. A fat tissue biopsy was performed in the suprailiac region in 20 male and 16 female pairs in order to determine mean adipocyte diameter and basal lipolysis as well as epinephrine maximally stimulated lipolysis (10−4 M). Twin resemblance in body fatness is clearly demonstrated by the analysis of the between MZ sibships over the within MZ shibship means of squares for all skinfold measurements, percent body fat and fat free weight (P < 0.01). Within MZ pair similarity is as high in female as in male pairs for body fatness. Moreover, members of the same twin pair resemble one another significantly for fat cell size and fat cell lipolytic activities, particularly when epinephrine stimulated. In female MZ pairs, additional studies with control over the menstrual cycle are needed to clarify the case of isolated fat cell basal lipolysis.

The incidence of preterm delivery among twin maternities in Oxford between 1973 and 1983, was 39.4%. Preterm delivery was more common in MZ than DZ twins, and this was associated with higher incidence of spontaneous rupture of the membranes associated with monozygosity.

According to the results found in literature Microcephaly — better Micrencephaly — is a syndrom with a very heterogenous pathogenesis which often remains unclarified. Its etiology, though occasionally purely exogenous, seems to be mostly hereditary in the sense of monomeric recessivity, as the experiences, so far rather scanty, of research in families and in twins show.

The so-called Microcephalia vera is to be considered identical with this mono-recessive form.

Our data may be divided in four groups:

Group I comprises 35 cases of verified or almost sure M. vera in 23 sibships. The diagnosis are mainly assured by clinical data and photos and in 4 cases by post mortems, 3 of them having been most carefully examined under the guidance of brain-anatomists like C. v. Monakow, M. Minkowsky and E. Grünthal whose publications in detail are referred to here. The Sex-Ratio in our cases (17 male and 18 female) is practically 1:1, therefore deviating considerably from that found in Japan and even more from that found in England and in Holland.

The application of Weinberg's sib-Method to our thoroughly studied, non-selected series gives the percentage of 24,2 ± 6,2 largely corresponding with the theoretical expectation for the assumption of simple recessivity.

A parental consanquinity was only found in 10 families though even the IV. - V. Canonical degree was also considered twice and though about a third of our patients originate from isolates. The number of I. and II. cousin-marriages occur but three times each (together 26%). Further, 1 case of incest between father and daughter is described.

The main complications in our cases of M. vera are epileptic fits and fits of excitement with aggressive tendencies. An encephalocele was found only once and other states of dysraphy nowhere prevailed; neither did cerebral tumors, phacomatosis and other systematised nervous affections, as well as mongoloid idiocy, disturbances of metabolism and somatic malformations. Also psychoses were not above the average in the kinships concerned.

General spasticity, a symptom found regularly in their cases by other authors was only met with in a minority of our cases. Possibly there may exist heterogenity in M. vera, which phenotipically manifests itself by the presence or absence of general spasticity.

Since in Switzerland by far not all cases of M. are interned, the frequency of M. vera is difficult to ascertain. About half of our patients died in early childhood and maybe many die through abortions, the gene involved being semilethal.

Growth and life-span can rarely be normal even in high-grade microcephalic idiots. Most of them, however, are undersized, exceptionally real dwarfs.

Among the non microcephalic sibs of our patients we found a considerable number of feebleminded and bordeline cases, showing — but not always — a lessened head-circumference. In the parents of our microcephalics, however, only exceptionally an intellectual deficiency was stated, more frequently as a matter of fact a lessened head-circumference. The very heterozygotes are not at all always characterised physically and mentally or even in one respect.

Our three other groups seem to refer to a secondary microcephaly and therefore are restricted to isolated cases. In one kinship a microcephalic boy is first cousin of an idiot with hydrocephaly. In another kinship with apparently simple recessive deaf-mutism and idiocy one patient shows microcephaly. In a third family with four sibs of clincally diagnosed cases of diffuse cerebral sclerosis each affected member was also microcephalic; here we have to deal probably — as the parents are II. cousins — with a particular specific simple recessive gene.

Plasma dopamine beta hydroxylase (DBH) activity was determined in MZ twins and in siblings of both sexes. The enzyme activities were found to be virtually identical in MZ twins. DBH activity was less similar in same-sex sibs, but still significantly correlated. These results indicate that plasma DBH activity is genetically determined.

The Authors have studied from the genetical point of view two family cases, mainly ophthalmological, with the following relevant findings:

Case 1) Proposita: female MZ twin, aged 13, suffering from facial paralysis on the left, with acute onset and persisting after two years, accompanied by the phenomenon of “Crocodile tears”. In the proposita, her co-twin, a single-born sister and the mother a parakinesia is found, consisting of a degree enophthalmus and of a narrowing of the left palpebral fissure when the left eyeball is adducted.

Case 2) Propositus: six-years-old boy affected by ocular albinism, as are 7 more males and 2 females in the family, while 3 females (including the propositus' mother) only present a partial depigmentation of the fundus (metaform). The transmission of ocular albinism has been found both through the female with a metaform and directly from father of sons.

The Authors take once more into consideration the problem of the hereditary nature of twinning on the basis of their own studies and of recent findings on human twinning induced by human menopausal gonadotropin (HMG).

Personal studies concern 3,221 cases of twinning drawn from the special files (“Gemelloteca”) of the Mendel Institute. On the basis of this material the Authors state that the occurrence of the cases of twinning in the paternal and maternal ascendancies of the twin index cases is significantly more frequent than would be expected in proportion to the frequency of twinning events in the Italian population.

This finding is in agreement with the hypothesis of the hereditary nature of the twinning phenomenon.

The same material is used to compare the frequency of twinning in the paternal and maternal families of twins. The observed frequency in the maternal families is significantly higher than in paternal families in which the frequency approximates population values. This finding leads the Authors to formulate the hypothesis that the twinning trait is limited to the female sex and is presently manifested by the occurrence of twins in the next generation. Thus studies on the frequency of twinning as a hereditary phenomenon should be based on the families of the mothers of twins.

Original studies also concern the 1,105 triplet sets born in Italy in the years 1952-1961. A study of the experimental and theoretical distribution of sex combinations in this triplet material allowed the Authors to prove that the experimental distribution differs from the theoretical one, based on the hypothesis of independence of the two types of zygosity (MZ and DZ). The absence of independence is considered a proof of the hereditary singleness of twinning.

The Authors further take into consideration cases of twinning induced in sterile women by administration of human menopausal gonadotropin (HMG): they observe that cases reported to date seem to be limited to dizygotic or plurizygotic twinning. These findings lead the Authors to believe that in this case hypophyseal FSH, responsible for ovulation, fails to find the usual pathway leading to standard uniparous pregnancy in the human species; the mechanism involved in such pathway is the object of some hypotheses of a hormonal nature. The Authors also believe that FSH stimulates not only the follicle but also follicular gametogenesis and even perhaps the division of the fertilized egg resulting in MZ twinning.

A new method of cross-sectional twin sampling from a population may be used in countries where authorities utilize electronic data processing of National Register data.

In Denmark, all National Register data are collected on magnetic tape. In January 1969 it was consequently possible, by the help of a 360-COBOL programme, to select all individuals in the Copenhagen area with identical birthday, month and year, and identical address. The selection was limited to the years 1943 to 1968.

Data from every person were tested against data from all other persons, to prove whether the person had one or more partners with identical data, i. e., twin, triplet, or quadruplet partners. Names and current addresses of the twins were written on self-adhesive labels intended for later correspondence. Had it been desirable, the computer might have produced, in the same operation, index cards and questionnaires ready for mailing. In the primary sample, a few “false” twin pairs from great collective housekeepings (as, for example, colleges) were included. These “false” pairs were excluded after comparing the partners surnames.

From the total population of 1 712 000 people, 4595 twin, 25 triplet, and 1 quadruplet sets were found. As many as 3754 twin pairs were born in 1951-1967. Of these, 34.68% were of opposite sex. Of the remaining pairs, 642 were born in 1943-1950, 28.19% being of opposite sex.

The use of epidemiological studies of twins as a means of determining the existence of genetic factors in various conditions is well known. To be of value, the zygosity of the twin pairs must be identified with as great a degree of confidence as possible. A method of determining twin zygosity, using concordance in general likeness, hair colour, hair type, eye colour, ear form, tongue roll and phenylthiocarbamide (PTC) taste sensitivity, was developed for use in a survey of 244 pairs of like-sexed twins aged 5 to 15 years. The results obtained and the problems raised when applying this method are discussed. The method was simple to apply to a large group of twin pairs, and monozygotic pairs were identified with a degree of confidence greater than 95%.