The old concept of constitution, which has been dominating Medicine until this century, has to be revised in the light of the development of Medical Genetics and of Clinical Genetics, this new branch which is applied at the beside of the single diseased.

The study of the family of the patient from a genetic point of view is both possible and precious. The basic principles of the hereditary analysis are recalled, and the Author especially stresses how useful it can be to consider the temporary virtuality of the hereditary unity, which he suggests to call chronon. The study of the chronon of the genes contained in the genetic background of the family enables to visualize many a possibility in the future of the patient, such as the mean age of onset for a hereditary disease, or the steps of extinction in the course of ageing.

The therapy of a hereditary disease may be conceived in terms of a substitutive therapy.

After having rapidly indicated Eugenics' tasks and aims, namely in the field of malformations, the Authors present a number of cases selected from the Mendel Institute Eugenic Counseling. This selection was made in order to show the various simple models of inheritance, while advancing hypotheses about more complex ones in the inheritance of malformations.

General conclusive remarks are made, and the need is stressed of the realization of meetings for the study of the morbid aspects of the various populations, in order to assemble an ever growing number of those notions needed by Eugenics for ever better diagnoses and prognoses.

Heredity in viroses has to be considered (i) from the standpoint of the specific virus which, like any living organism, presents heredity, variability and mutation, and (ii) from the standpoint of the human host, where the receptive conditions may be genetically controlled.

The heredity of disposition to poliomyelitis is also witnessed by the results of Gedda's twin clinical method as well as by the proportionality between the consanguinity ratio and the ratio of concordance of the infection in the family.

The heredity of disposition to trachoma has been studied in 775 families from Eritrea, the disease having been examined in parents and children. Statistic and genealogic analysis shows the existence of a disposition. The mating of an affected father to a nonaffected mother does not alter the frequency of the affection in the children, as compared to the case of the children of both nonaffected parents. On the other hand the affected father makes the frequency of the affection significantly rise in the children when mated to an affected mother. Such a behaviour is explained through a more frequent disposition in the children of parents both affected by one and the same disposition.

The study of the sample through the dimensions of the sibship, showing a constant nonaffected-affected ratio, independently from the above dimensions, also leads to assuming the existence of a disposition. This sharply contrasts with the epidemiologic concept of a higher risk, the higher the number of sibs.

The so-called endogenous psychoses, i. e. the manic-depressive pychosis and the schizophrenias have still to be treated like functional characters, as their probably existing somatic bases are still unknown. It may be granted that these two groups are genetically different, though there are — particularly in isolates — hereditary types of psychoses mixed with both manic-depressive and schizophrenic symptoms. According to the data of twin research, schizophrenias and cyclic psychoses have no common genetic background.

The very high concordance of monozygotic twins for schizophrenia is liable to prove the high importance of genetic factors, while it does not exclude accessorial environmental influences in its etiology.

A simple recessive inheritance, which seemed to be outruled by most authors, appears now to be possible according to Garrone (1962). Other authors (Slater, Böök) pleaded for irregular dominance of major genes with or without single accessory genes, and others even for an unspecific polygenic origin.

The term “ schizoid ” is vague and does not correspond to a satisfactorily clear conception either clinically or genetically. It may be the incomplete expression of a disposition to schizophrenia and more often that of a recessive gene in heterozygotic state or an incompletely dominant gene. Schizoid features which have been observed twice in children with trisomy-22 are not likely to have anything to do with schizophrenic psychoses.

Most probably the schizophrenias are heterogenic, but not with regard to clinical variations such as hebephrenia, catatonia, dementia simplex or paranoides. At any rate, we should not rely too much on the empirical hereditary prognosis.

The study of the occurrence of schizophrenia in isolates has the advantage that we have to do mostly with one and the same biotype and that we are able to trace the presumable genes throughout 8 and more generations. On the other hand the number of character-bearers is numerically limited.

In an isolate of eastern Switzerland with about 400 individuals of a highly inbred and fertile population, the frequency of schizophrenia is at least 1.75%. There are accumulations of the trait in some families and collateral lines. The oldest cases of presumable schizophrenics go back a hundred years; the more recent ones were or are interned in the two Cantonal asylums. The diagnoses in their records were controlled by prominent Swiss psychiatrists. Among the parents and sibs of those schizophrenics only a few can be judged as “ schizoid ” at a psychopathic degree.

The parental consanguinity of our propositi is about three times higher than the average of this population, which also contains 3.5% of undifferentiated oligophrenia being low-grade in 1%. The frequency of both schizophrenia and oligophrenia does not account at all for the relatively high number of 5 so-called “ Pfropf-schizophrenias ” (i. e., combinations of schizophrenias with inborn mental deficiency); however, Larsson and Sjögren found the same in a Swedish isolate.

While the 14 cases of sure or most probable schizophrenia in our isolate do not clearly show a monomeric recessive inheritance (since Weinberg's sibmethod gives a =10.4% and Bernstein's a priori-method a P = 3.0%), the undifferentiated oligophrenia of all degrees most probably depends on one specific simple recessive gene. It is not unlikely after all that the schizophrenias be inherited in the same way in this population, provided there is a considerably reduced manifestation of a mutated autosomal gene.

While I receive, with great joy and pride, the honorary degree of this University, commemorative celebrations to honor the Bohemian scientist Gregor Mendel are being held in the Czechoslovakian town of Brno.

One hundred years ago, Gregor Mendel announced his discoveries concerning the hybridization of “pisum sativum”, and opened to science the way to understand the principles underlying modern Genetics. I feel it my duty to recall with admiring devotion this great man, whose name is just as much connected with Biology, as Galileo Galilei's name is linked to Physics. All the more so, because the honorary degree conferred on me by the President and the Professors of Villanova University is a doctorate in Natural Sciences.

Two other reasons prompt me to recall the work of Mendel. One is that Gregor Mendel was an Augustinian monk, and such an exemplary one indeed, that he directed the Brno Monastery as Abbot from the forty-sixth year of his life to his death. In a personal letter addressed to the Augustinian General, Father Luciano Rubio, on the twentieth February of this year, Pope Paul the Sixth stressed the significance of the fact that the Augustinian Order had given to the Church and to Science such an eminent man. Now, there is no better place to recall the religious gifts and the scientific genius of Gregor Mendel than your University, founded and directed by Augustinian Fathers.

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.

In a family with 528 members, in 7 generations, 162 (47% of the 347 examined patients) showed a Waardenburg syndrome. The frequencies of the different signs are as follows: lateral displacement of the canthi interni and lacrimal puncta: 76%; hyperplasia of the nose root: 54%; hyperplasia of the eyebrows: 52%; deafness: 9%; heterochromia of the iris: 9%; partial albinism: 6%.

The AA. have undertaken a study on the familial occurrence of cancer cases in the families of 142 patients with cancer of the biliary ducts, and of 208 patients with cancer of the pancreas, in comparison with the families of equal numbers of healthy persons (controls). On the basis of the collected data, neither for the cases of cancer of the pancreas nor for the cases of cancer of the biliary ducts, a higher incidence of cancer (both same site or all sites) than in the families of the controls has been observed. On the contrary, a significantly higher incidence of cancer of the digestive system has been demonstrated in the families of the two groups of cancer patients taken together.

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.

A generalization of the F test is proposed to see how many independent components are statistically significant when the co-variances between DZ twin differences on several psychological tests are compared with similar co-variances for MZ twins. When applied to the 6 scores of Thurstone's Primary Mental Abilities test battery, at least 4 separate components were found to be significant independently. Then 4 components are tentatively identified as similar to, although not identical with, the Number, Verbal, Space and Word fluency scores. While the procedure bears some resemblance to factor analysis, it may lead to quite different results since it is based on the comparison of two co-variance matrices of twin differences.

In conclusion, it should be kept in mind that these results are based on small samples of MZ and DZ twins, so that a repetition of the study seems indicated. This replication is now in progress.

A case of bilateral clouding of corneal homografts in a 24-year-old woman 8 and 9 years after the respective operations, coincidentally with the second month of pregnancy, leads the Authors to a series of considerations and hypotheses on the immunological aspects of keratoplasties.

Differential diffusion of antigens to reach the antibody-forming sites, and of antibodies to reach the antigenic loci on the graft, through the endothelial barriers and the stromal layers, is held responsible for the peculiarities of corneal graft survival, especially in view of the different molecular sizes of antibodies and in connection with primary and secondary immunization. A series of experiments is currently being carried out to test the various hypotheses.

20 subjects with Morgagni-Turner's syndrome have been extensively investigated for structural or functional abnormalities of the urinary tract. This investigation was planned owing to the observation by Morgagni, who described the first case of gonadal agenesis associated with a congenital anomaly of the kidneys, and in consideration of the embryological connection between the gonadal and the excretory « Anlagen ». Moreover, to this respect, previous investigations have been very indicative. The patients were subjected to conventional X-ray examination of the urinary tract and to radionephrography with 131 I-hyppuran and, when necessary, to renal scintigraphy with 197 Hg-neohydrin. In a group of patients inulin and PAH clearances were also determined. More than half of the patients had important abnormalities: horseshoe kidneys (5 cases), pyeloureteral duplicity (3 cases), unilateral renal aplasia (2 cases), rotation of the kidneys (1 case); seven further cases showed pyelic dilatation and hypotonia associated with frankly abnormal 131 I-hyppuran nephrograms. 3 out of 4 cases, in which clearance studies were performed, showed marked reduction of glomerular filtration rate and renal plasma flow, even though conventional urography showed no pathological change. It is evident that the urinary tract is very often abnormal in this syndrome; the abnormalities are usually structural, rarely purely functional. Thus, it seems even more justified to indicate the syndrome with both the names of Morgagni and Turner.

A genetic study on a sample of patients suffering from essential hypertension has confirmed the inheritance of this disease. In single individuals and in families, especially in young female subjects, the same hereditary load often leads to the appearance of a vascular headache. In some family groups, the vascular headache seems to occur more frequently than in others. This fact suggests the hypothesis of a possible existence of factors able to favour the appearance of this trouble. After considering the data collected from the study of three generations of relatives of the hypertensive propositi, it seems possible to state that the hereditary load usually develops into vascular headache in young age, and hypertension in old age, while headache tends to disappear. This pattern, usually frequent, is not quite constant, and, in the same families, it is possible to find subjects affected with hypertension only, and others (also in old age) with headache only. Therefore, it is possible to think that the abovementioned diseases are pleiotropically determined by the same genetic factors, occurring in different ways, according to age, sex and other genotypic factors. The statistical analysis of the collected data suggests that such disease be inherited as a dominant monomeric autosomal trait, with a higher penetrance in old than in young people. Headache seems to prefer female subjects, while hypertension does not show any sex-preference.

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.

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 Authors have studied the hereditary etiology of myelinated nerve fibers of the retina and present two twin cases: one MZ pair concordant as to myelinated nerve fibers and to embryonic remains of the posterior capsule of the lens, and another MZ pair discordant as to myelinated nerve fibers and concordant as to epilepsy.

The rate of the total urinary 17-ketosteroids has been studied in twins of the two sexes (8 ♂ ♂ and 3 ♀ ♀ MZ, and 4 ♂ ♂ and 3 ♀ ♀ DZ, for a total of 18 twin pairs).

On the basis of this material it could be shown: (i) that the metabolism of the urinary 17-ketosteroids is genetically controlled for a quantum of 43.65%; (ii) that the secretion of the urinary 17-ketosteroids is correlated with age, and (iii) that a quantitative differentiation of the phenomenon exists in the two sexes.

A study on the relationships between rheumatic valvular heart diseases and the ABO blood groups has been carried-out on a sample of 1,047 patients distributed, according to their origin, in 10 different areas. A first analysis, accomplished on the basis of this distribution, indicates a highly significant negative association of rheumatic valvular affections with group O, in comparison with all other blood group phenotypes, both singularly or totally considered. It is also shown that no significant heterogeneity exists among the areas. Subsequently, a similar procedure is applied by distributing all the patients according to sex, received therapy (medical or sugical) and previous anamnesis (acute rheumatic fever, repeated acute tonsillitis, no signs). This second part confirms the association of the condition with A, B and AB blood groups, but no heterogeneity is demonstrated among the different classes of the second distribution.