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.

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.

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.

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 syndrome of ataxia-telangiectasia was studied from a genetic standpoint on a material consisting of 7 original cases from four families, and of 31 cases from the literature. A cytogenetic analysis in one patient showed the normal diploid chromosome number, while the application of Brugger's test showed a random distribution of affected members in the investigated sibships. The observed frequency of affected individuals corresponds to the one to be expected, assuming a recessive monofactorial inheritance of the syndrome. Considering the small number of consanguineous marriages observed between parents of affected individuals, the conclusion can be drawn that ataxia-telangiectasia is not so rare a condition as it is generally assumed. The responsible gene shows a pleiotropic and lethal effect.

The karyotype has been analysed of two subjects with mandibulofacial dysostosis (Franceschetti's syndrome), considering that the main anomalies of this condition are also present in other malformations for which the association with particular genomic or chromosomal aberrations has been demonstrated.

In both subjects, the karyotype was normal.

The comparison of the clinical and cytogenetic data of this malformation with those of others (trisomy-D1 syndrome, trisomy-18 syndrome, deletion-18 syndrome) provides further evidence of the complexity of the genie systems controlling the processes of individuation during embryonic development, and of their interferences. However, this also shows how difficult it is to obtain human chromosome maps through the study of the macroscopic phenotypic characteristics of certain chromosomal anomalies.

The author has systematized the hallucal dermatoglyphics in accordance with the pattern direction in whorl, longitudinal, transverse, and open-field patterns Neither sex difference nor any difference between the right/left foot could be demonstrated. A correlation with χ2-distribution mother/child gave for:

1. longitudinal/transverse pattern χ2=49.0;

2. longitudinal/whorl pattern χ2=12.3;

3. transverse/whorl pattern χ2=6.3.

Cytological studies have shown that Down's syndrome (“ mongolism ”) is the result of a chromosomal anomaly which occurs either in one of the parent's germ cells or at a very early stage in (embryonic) development of the affected individual. The chromosomal anomaly involves the occurrence of a third number 21 chromosome, in addition to the normal complement of two, either separately (i. e., trisomy-21) or attached to one of the other acrocentric chromosomes (i. e., translocation to one of the chromosomes numbered 13-15 or 22 — Denver Report, 1960). Epidemiological studies have indicated that numerous factors are related to, and may affect, incidence of the chromosomal anomalies resulting in Down's syndrome. Studies by Collmann and Stoller (1962a, b) imply fluctuations of annual incidence with a 5-6 year periodicity, a higher incidence in urban compared to rural areas and a clusteting of affected births in certain geographic regions. Collmann and Stoller postulated an “ infectious agent, probably a virus ”, to account for their data. No connection, however, can yet be drawn between such a hypothesis and the established cytogenetic anomaly. Periodic fluctuations in incidence, which are characteristic of recurrent epidemics (Gordon, 1962), have also been reported for congenital anomalies other than Down's syndrome, such as anencephaly, spina bifida, and hydrocephaly (Collmann and Stoller, 1962b; Guthkelch, 1962; Alter, 1962; Slater, Watson and McDonald, 1964).