Description is made of a family of which in three generations five members presented a rare osseous distrophy. Medical information was obtained for about 46 individuals of the 107 who constitute the family. The affection shows resemblances with both the Camurati-Engelmann disease and hyperostosis corticalis generalisata familiaris. It is inherited through a dominant gene.

Agreement prevails that MZ twins have higher concordance rates for cancer than do DZ twins. The exact genetic influence on concordance remains doubtful. Neither the patient groups nor the means by which data are analyzed are comparable. The naturally higher perinatal mortality rate among twins affects statistical analysis of diseases among surviving cotwins. Classification of zygosity among all studies of twins is not entirely reliable.

A review of published reports of cancer among twins notes concordance in a variety of tumors. Genetic factors appear to operate either in the concordance of the cancer or in the site of the specific tumors. A genetic origin of tumors in MZ twins is possible. Tumors, including type, site, and age of onset, affect MZ twins more than both members of a DZ pair.

Computerized permanent twin registers should be established for study of prospective follow-up of large twin populations. Suggestions are made for implementation.

A total of 116 cases of multiple pregnancy has been observed in a 5-year period. MZ twin pregnancies appear to be significantly increased in the maternal age group 31-35. Also significant is the higher frequency of abnormal cycles in MZ twin pregnancies. Family incidence of twins is more significant in mothers of DZ as compared to MZ twins.

An interdisciplinary study, in adult twins and their family members, of the genetic and environmental determinants of complex physiologic functions is in progress. This report summarizes our initial studies of the control of the level of systolic (K1) and diastolic (K5) blood pressure in 202 monogygotic (MZ) and 121 dizygotic (DZ) twins, their spouses and their children. Correlation coefficients for blood pressure were adjusted for the covariates age, sex, body mass index (wt/ht2) and screener, all of which significantly augment most correlations. These adjusted correlation coefficients in MZ twins are 0.5 for both K1 and K5 blood pressure. For DZ twins, the adjusted correlation coefficients are 0.21 (K1) and 0.24 (K5). MZ twin-offspring adjusted correlation coefficients are higher than MZ twin-niece/nephew adjusted correlation coefficients (0.12 and 0.06, respectively, for K1; 0.20 and 0.13, respectively, for K5), despite the genetic identity of these relationships. That environmental factors may explain these differences is suggested by other differences in adjusted correlation coefficients that are greater than those predicted by the degree of genetic similarity. In addition, we have assessed the relationship between two biochemical-physiological processes, the urinary excretion of kallikrein and transport of sodium in the erythrocyte (the sodium countertransport and the sodium-potassium-chloride cotransport systems), and blood pressure control, since both have been implicated in the control of blood pressure level. Although we found evidence for substantial genetic control of both phenomena, we were unable to establish any correlation between either function and the level of blood pressure in our normotensive subjects.

These data point to the operation of three broad categories of control of level of blood pressure: constitutional factors (age, sex, body mass), genetic factors and environmental factors. The identities of the genetic and environmental factors are unknown at this time.

No matter what our everyday activity in the mental health field, we can say with conviction that the function of a new superspecialty such as Psychiatric Genetics, the subject of this late-morning session, is profoundly influenced by contemporary cultural, social and political conditions as well as by the never-ending challenge of scientific conquests. Evidently, therefore, any attempt to formulate a concise and generally acceptable definition of such a modern hybrid discipline is no less difficult than it is to work in it. Actually, since the two parental sciences deal with equally absorbing, intricate and still rather speculative aspects of human existence and health, it would make little difference here if the given definition were developed within the framework of psychiatry or that of human genetics. What is certain only is the empirical observation that there are very few workers in this particular field of superspecialization, who are not prematurely grey or otherwise debilitated.

In order to facilitate a fruitful discussion despite these considerable difficulties, it may be advisable to use a description of psychiatry and its various schools of psychotherapy, which is plain in its formulation and is focused on appropriate medical concepts and techniques from a professional standpoint. This selective procedure is justified, since in many recent conferences on the functions of clinical psychiatry, increasing emphasis has been placed on two general professional requirements. One of them is that psychiatry should never be “a field apart from other areas of scientific discourse”. The other criterion is that a psychiatrist be “a good physician first and always… capable of acting as the trustworthy friend, the wise counsellor, and the discreet and skillful servant” of people in distress.

This paper summarizes some studies recently carried out in this Institute in the field of cancer chemotherapy.

Three main groups of data are reported:

a) different sensitivity to chemotherapy of the same tumor transplanted in different sites of the body;

b) a method to study cancer dissemination as a basis for cancer chemotherapy;

c) a system to perfuse tissue culture with the blood of living animals as an approach to study duration of action of antitumoral drugs.

On the basis of the parameters of gene stability suggested by Gedda-Brenci's model on the Ergon/Chronon System, a mathematical and a stochastic model of gene decay are worked out.

The report explains how twin-studies may affect the science of population, both directly by their frequency and determining factors, and indirecdy in as much as twins provide a useful research method to study the physical and psychological traits which identify a human population.

It is possible, in fact, through the method of intrageminal-in-tergeminal comparison and through other methods, to study the population's normal and pathological traits.

As far as diseases are concerned the twin method affords the chance to discover or to reassert the hereditary nature of many diseases as well as the hereditary aspects of morbid receptivity and reactivity in the esogenous diseases; furthermore, it is possible to probe deeper while studying hereditary diseases especially in the fields of phenogenesis, variability and nosological classification.

The study of psychological traits in twins makes it possible to identify the instinctive tendencies and the hereditary components of the mental functions; also the study of learning capacity and of psycho-somal phenomena based on heredity.

In order to make it easier to complete twin studies on an increased number of twin sets, statistical surveys and social provisions of various kinds in favor of twins (which already have yíelded good results in Italy) are advocated.

Objective: data on the prognosis and management of multifetal pregnancies are of vital importance, particularly when the option of selective termination is considered. The present study details the obstetric management, neonatal outcome, and follow-up data of 65 quadruplet pregnancies in France.

Methods: to conduct the study, a questionnaire was sent to families registered with the National Association Helping Parents of Multiple Births (Association National d'Entraide des Parents de Naissance Multiples, A.N.E.P.N.M.).

Results: of 116 questionnaires sent to families of quadruplets born between 1972 and 1988, 65 were received. Of these pregnancies, 58 were obtained with ovulation induction agents, 2 with IVF (in vitro fertilization) and GIFT (gamete intrafallopian transfer) and 5 were spontaneous. Diagnosis was made prior to 13 weeks gestation in 87.2% of cases. Most mothers were hospitalized prior to delivery – mean duration of 47 days. The mean gestational age at delivery was 31.2 ± 3 weeks with a prematurity rate of 97%. Cesarean sections were performed in 51 cases and vaginal deliveries in 14. Neonatal and perinatal mortality rates were 68 and 104 per 1000, respectively. Birthweights of quadruplets ranged from 760 to 2455g with a mean of 1615 g.

Conclusion: management of quadruplet pregnancies in France consists of early diagnosis, echographical and clinical monitoring, early reduction of maternal activity and cesarean deliveries. Our management of such pregnancies is of high quality as reflected by our obstetrical results. Lack of adequate management, as perceived by families of quadruplets, exists at two levels: a psychological (lack of psychological support) and a financial (lack of specific help).

Im folgenden soil über die Ergebnisse von systematischen Familienuntersuchungen berichtet werden, die ich bei unausgelesenen totgeborenen und im ersten Lebenshalbjahr verstorbenen Kindern mit letalen Anomalien der Körperform durchführen konnte.

Der Begriff « Anomalien der Körperform » wird dabei im Sinne meines Lehrers v. Verschuer für typische, oft erbliche Missbildungen einschliesslich Kombinationsmissbildungen mit Veränderung der äusseren Körperform gebraucht, die ich als Todesursache unter den in den Jahren 1937-39 im Pathologischen Institut der Universität Frankfurt-Main erfolgten Sektionen finden konnte. Eine statistische Auswertung der Gesamttodesursachen war bereits früher erfolgt (1942).

In einer umfangreichen Monographic « Familienuntersuchungen bei missbildeten Totgeborenen und Frühverstorbenen » sollten die im folgenden zu besprechenden Befunde zusammen mit anderen letalen Missbildungen (Herzmissbildungen, letalen Hernien, Ektopien, Missbildungen des Magen-Darmkanals, der Haut und der blutbildenden Organe sowie auch Mongolismus) Anfang 1945 als Ergänzungsband der Zeitschrift für menschliche Vererbungs- und Konstitutionslehre erscheinen. Leider ist die bereits ausgedruckte, fertige Arbeit am Ende des letzten Krieges der Zerstörung von Würzburg zum Opfer gefallen. Bei den gegenwärtig beschränkten Druckmöglichkeiten in Deutschland habe ich unter dem Titel « Frühletale Missbildungen und Hereditat » bisher lediglich ein kurzes Referat der Arbeit geben konnen. Für das grosszügige Angebot von Herrn Prof. Dr. L. Gedda, einen Teil der Arbeit in die Acta geneticae medicae et gemellologiae aufzunehmen, möchte ich deshalb meinen ganz besonderen Dank aussprechen.

A description is made of a Brazilian family of white ancestry in which five individuals presented the fibrous dysplasia of the jaws known as cherubism. The information obtained involves seven generations in a total of 75 individuals. 23 of these were examined by the authors and a report about a deceased person was confirmed by photograph. The affection in this family is probably conditioned by an autosomal dominant gene with variable expressivity.

A 38-year-old woman, gravida 5, para 3, with a triplet prgnancy discordant for anencephaly, is reported. The diagnosis was made prenatally by ultrasound. Autopsy of the anencephalic member revealed small adrenal glands with absent fetal cortex, and a coincidental tetralogy of Fallot. Studies of the histocompatible lymphocyte antigens of both parents were performed and they failed to demonstrate HLA B-27. The literature on anencephaly in triplets is summarized. The association of congenital heart disease and HLA B-27 with anencephaly is discussed.

Our data show that oxytocic perfusion should be liberally given during twin pregnancy labor, since its use is correlated with lower fetal mortality, especially of the second premature twin. This therapy might act, namely, by reducing the number of second-twin abnormal presentations. In our series, the higher mortality rate associated with lengthening of time interval between both births could be attributed to second-twin abnormal presentations. However, mortality rate versus time interval in spontaneous twin deliveries warrants obstetrical management providing second-twin birth within 15 minutes.

The concurrence of two experiments of nature, twins and congenital birth defects, provides a unique population for the elucidation of nature-nurture questions. Although the concurrence of twins with clefts is not common, their frequency in the aggregate of international reporting is sufficient to allow for meaningful studies.

In a recent conference on the genetics of cleft lip and palate, Fraser (1968) summarized the state of knowledge regarding etiology. The following quotation from his report is pertinent to the present paper:

1) In the majority of cases, cleft lip or cleft lip and palate [CL(P)] represents a quasi-continuous variant, or threshold character of multifactorial etiology. For cleft palate [CP] there is less convincing information;

2) Observations on arch form, face shape, body asymmetries and developmental variables suggest that such variants may underly the predisposition to clefts;

3) Twin studies may be useful in identifying the physiognomic factors predisposing to facial clefts.

With these concepts in mind, we initiated an analysis of 19 twin pairs selected from the continuing longitudinal growth study which began at our Center in 1949 (Pruzansky and Lis, 1958).

The suitability and reliability of the Rh-Antigens is being discussed in details in the light of a great number of forensic serologic tests carried out in our Institute in cases of discussed parentage (859 contracting parties, 1251 males involved).

The frequency of paternity exclusions observed does greatly conform with the frequency expected. Differences noted are either very small or are in the range of standard deviation.

Authors emphasize that it is necessary to repeat the test especially if a criminal case is concerned or if an accused father can be excluded.

In a lecture to a group of physicians of sporting societies the Author presents the phenomenon of the family habit of sporting practice as the signo of the existence of a hereditary basis for sporting proficiency.

Referring to research by other Authors, and especially by Grebe, the Author relates the most significant case histories of family sporting practice afforded by Italian sports.

The hereditary transmission probably takes place through a mechanism of dominance; the Author suggests the method which can be employed in order to enact a genetical study of sports and of athletics.

A detailed description is given of the study performed in a pair of monozygotic Negro twins both suffering from hemophilia B; the bibliography is also reviewed about the occurrence of hemophilia in twins. The zygosity determination was performed utilizing anthropometric measurements, observation data, finger and palmar prints, seven systems of blood groups and five other genetic systems. The twins present a great similarity in the hemorrhagic symptoms, coagulation tests and Christmas factor level, but morphologic and physical differences due to the disease. These differences are explained by the diversity in the medical-hospital care which both received.

The incidence of pterygium was studied in an isolated highly inbred fisher population. A clinical and hematological examination was performed and the blood chemistry was studied. Genealogical tables (pedigrees) were prepared for all probands and the degree of consanguinity in their parents stated. Of the total of 479 subjects studied by random sampling, 19 (4 per cent) had pterygium with a relatively high manifestation age. No linkage was detected between the genes for the blood group systems, serum groups etc. and the gene for pterygium. Increased capillary fragility was established in 10 probands. Capillary permeability was studied in 2 probands by the concentration in the anterior chamber of intravenously administrated fluorescein, and the test was found to be weakly pathological in one of them. The serum cholesterol level was elevated in 5 of the patients studied. Ophthalmological examination indicated the accumulation of degenerative eye diseases. Pingueculum showed a more pronounced development in 10 of the 17 subjects examined than in the rest of the population. The possibility of recessive transmission of the hereditary predisposition is discussed with reference to the high frequency of inbreeding and the accumulation of pterygium within the isolated population. According to the special frequency-raising peristasis conditions in an outer archipelago community and to the mendelian segregation rate, a not sex-linked, simple dominant gene, with low penetrance and no selective disadvantage for the pterygium seems to be the most plausible explanation. Because of the late manifestation age, pterygium was observed only in 2 generations. The expressiveness of the gene was unsteady and asymmetry of pterygium in the eyes of the probands is not uncommon.

The first-degree relations of 433 rheumatic propositi were examined for evidence of rheumatic fever (RF) or rheumatic heart disease (RHD). The families of 470 control propositi were examined in identical fashion. Of the total propositi, 378 propositi were matched with 378 control propositi for sex, age group, and ethnic community (European or Afro-Asian origin). Of 738 sibs of rheumatic propositi, 19.6% had RF or RHD and of 586 sibs of controls, 3.1% had RF or RHD (P<0.001).

In the matched families 2,985 first-degree relations of the propositi were examined: 142 had RF and 141 had RHD, a total of 9.5%. In the members of the families of the rheumatic propositi 232 rheumatics were found in 1,486 first-degree relations (15.6%), while in the control families 51 rheumatics were found among 1,499 (3.4%).

Comparisons and analyses were made of expected and observed numbers according to sibship size using the method of truncated analyses (Lenz-Hogben method). This analysis supported the hypothesis of a simple mendelian recessive inheritance. Unbiased estimates of P, the population frequency of affected individuals, were consistent with the value P = 0.25, expected for a mendelian recessive character. The rheumatic fever clustering in families in this study was compatible with a simple recessive mendelian inheritance.