Come genetista e direttore di Acta Geneticae Medicae et Gemellologiae sono lieto di dedicare il « Supplementum primum » alla figura del Prof. Otmar Freiherr von Verschuer in occasione del suo 60mo compleanno.

Mi muove a far questo la riconoscenza, perchè quando elaboravo il mio trattato sui gemelli ho trovato un singolare aiuto nel consiglio del Prof. O. von Verschuer che egli mi ha offerto con quella profondità e competenza che caratterizzano il suo ingegno e con quella nobiltà e generosità che distinguono il suo cuore.

Ed anche quando l'Istituto Mendel, che ho l'onore di dirigere, si è presentato all'attenzione degli studiosi di genetica ho trovato immediata comprensione ed appoggio nel Prof. O. von Verschuer, il quale ha preso parte come relatore al « I° Symposium » di Genetica Medica organizzato in occasione dell'inaugurazione dell'Istituto (Roma, 1953).

Se riferisco questo non è solo per il doveroso ricordo di una personale esperienza, quanto per mettere in luce un aspetto molto importante nella vita del Nostro che dimostra con la signorilità e la generosità del sapere la sua ricchezza interiore, giustificando in questo modo l'affetto di cui è circondato e facendo comprendere come mai egli abbia potuto crescere una Scuola così fedele alla sua Persona e cosi feconda nella produzione scientifica.

Kongenitale Missbildungen, die sich auf die Fruchtbarkeit auswirken und sie entweder beeinträchtigen oder sogar völlig annullieren sind diejenigen, die die Empfängnis, die Schwangerschaft oder die Existenz eines lebensfähigen Geschöpfes verhindern. Diese Missbildungen, die ich der Kürze halber « antifertile Missbildungen » nennen will, sind Kongenital d.h. schon bei Geburt vorhanden.

Die Besprechung des Stoffes erfordert eine Aufteilung in vier Abschnitte:

1. Allgemeine antifertile Missbildungen;

2. Lokale antifertile Missbildungen bei der Frau;

3. Lokale antifertile Missbildungen beim Manne;

4. Antifertile Missbildungen, die das Leben der Frucht verhindern.

Die allgemeinen antifertilen Missbildungen beim Manne und bei der Frau können gemeinsam besprochen werden. Es handelt sich um missbildende kongenitale Krankheiten, die die Fertilität durch verschiedenartige Mechanismen beeinflussen: durch hormonale Störungen, Strukturveränderungen, psychogene oder neurologische Veränderungen usw.

Ich beziehe mich hierbei auf Missbildungen, die ein ganzes System befallen, wie Mongolismus, das Syndrom von Morquio, das von Marfan, von Lawrence-Moon-Biedl, der idiopathische Infantilismus usw., die alle mehr oder minder mit Unterentwicklung der Genitalien und häufig auch mit örtlich spezifischeren Missbildungen, wie zum Beispiel Kryptorchismus, einhergehen.

Report about examinations in the families of 24 children with severe, lethal malformations of the heart. At all probands, who had died before 6th month of life, the, cause of death could be insured by autopsy.

Under 16 children with lethal defects of the septum 6 suffered from mongolism (additional one with enterocystom of oesophagus, one with double inguinal rupture, one with cleft palate and one with microcephaly and atresia of the duodenum). In none of these families any sign for heredital cause or « ovarial insufficience » of the mother could be found.

In the families of 10 children with defect of the septum without additional malformation two times the clinical examinations of the mother showed distinct symptoms of heart decompensation without evidence for acquired heart diseases. In two other families beside the probands other family-members with inborn heart diseases could be found, one time an autoptical proved defect of the septum at a cousin of our probands father.

During these families seem to show heredity of lethal defects of the septum in an irregular dominant inheritance, only one time in an «isolated » case of lethal defects of the septum the cause of the malformation may be seen in severe bleedings of the mother during pregnancy.

In an earlier report about similiar examinations two siblings could be found, one of them had only a defect of the septum, the other had beside a defect of septum, a severe harelip and cleft palate, a hernia diaphragmatica, a hypoplasia of the fingers and a microcephalia combined with arhinencephalia. The father of another child with a defect of the septum suffered from coloboma of the iris.

It is supposed, that there are several gens to septum defects, that means Heterogenie. Polyphenical effects of the gens result differential forms of manifestation, not only at the heart. There were no differences found on homozygotics and heterozygotics.

Among 8 children with differential other malformations of the heart (5 cases of severe stenosis of the aorta, 1 case of malformation of the pulmonal valve, 1 case of trasposition of the big arterias) only one time could be found the same anomaly (open foramen ovale, open ductus arteriosus) on two cousins (each of them have an non dissecated brother with equal clinical symptoms). Because the parents were non blood-related also in this family an unregular dominant inheritance of the anomalies at the foramen ovale and the ductus arteriosus seems probable.

Systematical examination in families with lethal malformations are further equal necessary as explications of pregnancy harms for exclusion of exogen factors.

In this paper a counterpart is given to the data of our investigation about the incidence of infantile amaurotic idiocy (Tay-Sachs) in Switzerland, published here in 1954. The term «the-saurismose» is rather unclear and had to be critisised by Letterer. The diagnose of all lipidosis is more difficult than of any other genetic character, as neither a thorough clinical and histological examination nor the chemical analysis of the brain and the big abdominal organs (spleen, liver etc.) is sufficient; it ought always to be completed by the modern histochemical method at least if we want to separate the M. Niemann-Pick from the M. Tay-Sachs. The quarrel between the « unitarists » and the « dualists » concerning the independence of these two phosphatid-lipidosis does not seem to be ended definitely by chemical analysis of the affected organs. Undoubtfully these two very similar diseases must have many common traits in their pathogenesis. This does not mean, however, that they do not depend on 2 different genes, may be working at the same pheno-genetical chain (Klenk), perhaps there is a pseudo-allely, which as a matter of fact can hardly ever become proved in men. This author showed that the M. Niemann-Pick is regularly characterised by a high percentage of sphingomyelin whilst in the M. Tay-Sachs the gangliosids prevail. But recently this difference is regarded to hold only quantitatively. Therefore we have to look for genetical proofs of the independence of these two lipidosis. An observation of van Bogaert in his famous pedigree of the family Mi. and another less convincing of Driessen show that among the children of the same parents cases of both these lipidosis can appear. Since both these families are of Russian respectively Polish-Jewish origin, coming from a not very big area in which these lipidosis were found relatively very often, these two instances also could be explained by mere coincidence.

Our Swiss cases which all happened in families of non Jewish origin do not show sibs the one of whom had M. Tay-Sachs and the other M. Niemann-Pick, nor were combinations of both lipidosis observed. Unfortunately excepted one, namely that of Baumann, Scheidegger & Klenk, none of our cases has been examined with all the modern methods. These 3 specialists established the theory that we deal in the M. Niemann-Pick and M. Tay-Sachs with specific cellular dystrophies and not an overloading of the blood with certain lipids, as was supposed by Pick: For, all values of blood-chemistry, principally of the total amount of fatty acids as well as of cholesterol and of anorganical phospor used to be normal in the serum of those patients. The data published by U. Pfändler could become disguised as rare exceptions or consequences of alterations in a no more fresh serum. His conclusions with regard to the pathogenesis and the way of hereditary transmission cannot become adopted neither for the adult, nor for the infantile forms of Niemann-Pick.

The facts found by us and others clearly speak in favour of a simple-recessive transmission, at least for the infantile forms of M. Niemann-Pick, the same has been proved by us for M. Tay-Sachs. Videbaeks pedigree with parents of the 2 children with M. Niemann-Pic being first cousins, is not to be interpreted otherwise. Of our Swiss families with M. Niemann-Pick 3 contain each 2 fraternal and 3 isolated cases; parental consanguinity was found 4 times but not very close though 5 of these families come from isolates. The gene concerned therefore cannot be too rare. Like the other authors we did not observe secondary cases in collateral lines. The oldest of our patients reached the age of 3½ years. There is no higher incidence of other hereditary diseases, especially with regard to metabolism, in our 6 Swiss families.

From the clinical standpoint there is to mention that 4 of our 5 cases studied in detail showed the typical red spot in the region of the macula retinae; one case showed a complete atrophia nervi optici and another an atrophy of the temporal parts of the papilla nervi optici. In most cases a demencia or «imbecility » was noted, a fact which suggests the participation of the brain in the processus of the specific thesaurismosis. Unfortunately, however, the brain has but once been examined with the modern histochemical methods.

1. There is probably no special hereditary disposition for the localisation of the tuberculosis at the skin.

2. The partial selection of the hitherto made casuistics of twins explains the contradiction to the literature.

3. The general tuberculosis is in the sense of Diehl and v. Verschuer preponderating concordant by monozygotics twins and discordant by bizygotics twins.

The Klippel-Trénaunay-Parkes Weber-syndrome (K.T.W.) is a congenital malformation with partial gigantism (osteohypertrophy), naevi and varicose veins in the fully developed trias of symptoms. According to arterio- and phlebographic findings varicose veins are usually the result of mal-and deformations of the deep venous system or arteriovenous anastomosis, rarely of the arterial system alone.

In a critical consideration of all hypotheses about aetiology and pathogenesis of the K.T.W.-syndrome is discussed that there is no satisfactory explanation for the assumption that the syndrome is a exogenous malformation.

It is pointed out that so far there have been no family investigation of a greater extent. The statistic survey of the existing family investigations showes that the K.T.W.-syndrome is most variable in its phaenotypical manifestation and also has a strong intra-and interfamiliar variability. Heredopathologically is suggested that apart from a weak (?) principal gene secondary genes are essential for the manifestation. The mode of inheritance may be either dominant or recessive. The existence of various biotypes is considered probable. It is proposed to count the K.T.W.-syndrome into the group of the ectome-sodermal malformations (Oehler), the hamartomata (Wohlwill), the phacomatoses (van der Hoewe) or the neuro-cutaneous syndromes. 2 own cases are described.

In this paper an unselected series of 19 twins with migraine is reported. The findings in 13 pairs with ascertained twin diagnosis, 3 MZ and 10 DZ, are preliminarily summarized. With regard to typical migraine, only 1 MZ pair was concordant, a minor degree, of concordance was seen with all MZ and 3 DZ pairs. Regarding a distinct picture of vegetative dystonia, all MZ and 2 DZ pairs were concordant. On the basis of these results it can be assumed that various etiological factors are responsible for the manifestation of hemicrania. The hereditary basis seems to lie in a vegetative, diencephalic, dysregulation. Besides, the clinical manifestion is determinated by various preformative influences of an endogenous or exogenous nature.