The authors have investigated the genetic conditioning of malformative phenomena in the series of twin pairs identified by the Italian Institute for Vital Statistics in the five-year period 1961-1965 (approximately, 55000 twin pairs).

For the present study, an original theoretical model has been chosen, that makes the classical twin test of comparison between twin series different as to zygosity be applied to twin series different as to sex composition.

The resulting analysis enables the authors to formulate a hierarchical classification of many of the malformations listed by the Italian Institute for Vital Statistics, according to their degree of genetic conditioning.

Beautiful and brilliant, content and capable, skillful and successful, these and multiple other adjectives may be used to describe persons on a family tree of Eng-Chang, the original Siamese twins (Fig. 1). These men chose the State of North Carolina for homes, and are considered among its most renowned citizens. They had some of the above characteristics and their descendants shared others.

Data upon six generations of Eng-Chang families — some verified by their 1836 pamphlets, others as recent as 1969 court records in their county residence — are shown in the following table:

Fig. 2 shows second and third generations in family groups made in the summer of 1865. Nine of Eng's 11 children are shown; 2 had died young. Likewise, 9 of Chang's 10 children are seen; one was born in 1868, as certified by Edinburgh's famous Prof. James Y. Simpson (1869). Two sets of twins, not joined, are recorded in their descendants. Though some members on this family tree are difficult to certify, the data available in these six generations are by far the most comprehensive found. Chromosome and other genetic studies are being initiated and pursued in anatomy departments of American and Thai Medical Schools.

Molto spesso la genetica si è interessata delle malformazioni allo scopo di evidenziare il « quantum » di eredità che interviene nel determinismo morboso, specialmente quando la patologia denunciata è causa di grave alterazione del fenotipo.

Lo studio attuale vuole invece valutare l'importanza dell'eredità in un settore meno impegnativo della patologia malformativa, ma a nostro avviso assai diffuso, e cioè il peso dell'eredità sul determinismo di: (1) palato ogivale; (2) valgismo delle ginocchia; (3) malformazioni genitali; (4) piedi piatti; (5) malformazioni della colonna vertebrale; (6) malformazioni dentarie; (7) malformazioni delle dita; (8) malformazioni craniche.

Ben note sono le difficoltà che si incontrano in campo umano per l'impossibilità di procedere ad una sperimentazione diretta, ed è quindi il metodo gemellare ad apportare un contributo essenziale nella valutazione dell'eredità e dell'interazione di fattori paragenetici ed ambientali sull'evento patologico, mediante lo studio delle coppie gemellari MZ e DZ.

Nel nostro caso abbiamo raccoito 240 coppie gemellari delle quali 120 MZ e 120 DZ, che sono state distribuite in otto classi corrispondenti alle otto patologie descritte a seconda della rispettiva presenza in entrambi o in un solo gemello.

La rencontre et la fusion plus ou moins étendue des aires embryonnaires jumelles conduit à la pagisation; les possibilités de fusion de deux embryons jumeaux, ou bien de duplication partielle d'une aire embryonnaire, conduisent au même résultat: celui de malformé non-viable et inutile, mais instructif en tant qu'expériment naturel d'embryogénèse.

Nous présentons un céphalothoracoomphalopagus, dont l'étude nous a intéressé, tant par l'inventaire des malformations qui ont accompagné la pagisation, que par la symétrie somatique parfaite présenté par ce genre de monstre à double origine égale (isodyploterata).

Une seule tête, avec deux proéminences occipitales et deux visages opposés; un seul cou; un seul tronc avec deux colonnes vertébrales et deux région thoraciques antérieures; un seul abdomen recouvert d'une mince paroi, qui, loin d'assurer une bonne contenance, permet aux viscères de descendre comme dans une large poche célosomique; un seul cordon ombilical. Quatre membres thoraciques et quatre membres pelviens symétriques normaux (octomel); rachischisis lombosacrale avec méningocèle chez l'un des fœtus; imperforation anale du même côté (Fig. 1).

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).

Nella presente nota viene data una descrizione essenzialmente clinica delle malformazioni rilevate in una coppia di gemelli DZ ricoverati presso il Centro Auxologico Italiano di Piancavallo.

Nati da parto distocico per placenta previa, espletato mediante taglio cesareo. Figli primogeniti di genitori sani, non consanguinei; all'età del concepimento, padre e madre avevano, rispettivamente, 30 e 24 anni. Il fratello, di 4 anni, è apparentemente sano. Nella parentela non si rilevano anomalie ossee.

Franco. Gruppo sanguigno O, Rh+; peso neonatale 3.55 kg; ernia scrotale congenita e frattura ostetrica del femore dx. A 13 anni e 4 mesi: scadenti condizioni di nutrizione (166 cm, 54.9 kg); asimmetria facciale con prevalenza dell'emifaccia sn.; deviazione setto nasale verso sn. con aspetto di facies scoliotica sn.-convessa; asimmetria toracica con spiccata prominenza del manubrio ed affossamento del corpo dello sterno; scoliosi ad S del rachide cervico-dorso-lombare, confermata dall'esame radiografico della colonna vertebrale, che consente di accertare, inoltre, un dismorfismo di D1-D2-D3 con schisi dell'arco in D1. L'esame radiografico della gabbia toracica mostra deformazione asimmetrica con incisura al terzo medio del profilo esterno sn. e bifidità posteriore della terza costola.

Sergio. Gruppo sanguigno B, Rh+; peso neonatale 3.05 kg. Palatoschisi trattata con un intervento correttivo duplice a 7 mesi e a 2 anni. A 13 anni e 4 mesi: scadenti condizioni di nutrizione (170.7 cm, 50 kg); asimmetria facciale per prevalenza dell'emifaccia sn.; deviazione del setto nasale verso dx.; irregolarità della volta palatina per gli esiti correttivi della palatoschisi; spiccata prominenza del manubrio ed affossamento del corpo dello sterno. L'esame radiografico del rachide rivela schisi incompleta dell'apofisi spinosa di D5, senza deviazioni scoliotiche della colonna dorso-lombare. Schisi paramediana sn. del palato con anomalie d'impianto dei denti all'arcata superiore.

Chromosome analysis was made on peripheral blood and bone marrow cells of bovine twins, triplets and quadruplets of different sex. Both sexes showed 60,XY/60,XX chimerism. The percentage of cells with XX and XY chromosomes varied from animal to animal, ranging from 10% to 76%. The differences between the peripheral blood and bone marrow were relatively small. Some males had a majority of cells with female heterochromosomes.

This chimerism presumably also affects other tissues, because the progeny of a bull with a 60,XX/60,XY pattern and 68% of cells with XX heterochromosomes showed a marked shift in the sex ratio, namely, 68 ♂: 100 ♀. This evidence suggests that the chimerism affects spermatogonia, which, nevertheless, are able to produce fertile spermatozoa.

Immunological studies of the quadruplets showed identity of red blood cell antigens in the A, B, C, FV, L, SU, Z and Ŕ/Ś systems. Cross transplantation of skin grafts among the quadruplets produced not even traces of antibodies to these red blood cell antigens, and no cytotoxic antibodies to peripheral blood lymphocytes in these animals.

Several studies have appeared in the literature to support the hypothesis of a differential incidence of twin births according to the antigenic structure of maternal erythrocytes (Gedda, 1961).

Osborne and DeGeorge (1957) wrote that twin births exhibit a higher incidence when mothers belong to group O, as compared to other groups within the ABO system; a similarly increased incidence of twin births was indicated for rh-negative mothers within the Rh-Hr system.

The availability of a large number of immunohematological data concerning twin pairs and nontwin individuals examined in our Institute have encouraged us to verify whether this material could reveal some a posteriori effect of the selective tendencies that have been related to the parental level.

Limiting our study in this phase to the ABO system, we have collected data on 1190 twin individuals and 1454 nontwin individuals, for all of whom the ABO blood group had been recorded.

The first step in our analysis was the perequation of the nontwin distribution to the twin distribution, obtaining the figures reported in the column “controls” in Tab. I.

The Xg blood group system is unique in that it is the only blood group antigen which is controlled by a gene residing on the X chromosome. There are six possible mating types in X-linked dominant inheritance, such as the Xg system represents. One of these types is of particular interest in this presentation, even though it amounts to only 6% of possible matings, assuming the usual western Caucasian gene frequency of the Xg system. In this mating type, an Xg(a+) father, whose X chromosome is designated as +, mates with an homozygous Xg(a—) mother (Fig. 1). The offspring of such a mating, if female, will be incompatible with their mother, since they have received their father's Xg(a+) X chromosome. Male offspring are of course compatible, since they receive their mother's Xg(a—) X chromosome and their father's Y chromosome. It follows that any biologically significant materno-fetal incompatibility with respect to the Xg system might lead to preferential loss of daughter conceptions.

The present paper deals with data collected during the course of a study of twin pairs who were participating in an ophthalmologic investigation. The twins were classified as MZ or DZ on the basis of their blood types (ABO, MNS Rh, Kell, Duffy, etc.), physical likenesses, and dermatoglyphic findings. The results expected of Xga testing, assuming random mating and no selection, were calculated by Li's method (1955), using the gene frequency of 0.65 for the Xga allele.

The serum levels in different subjects of the classes and subclasses of Ig are considerably variable. The influence of the environmental factors on Ig concentration is well documented; however, direct data on the influence of genetic factors are lacking.

To this aim, the Ig serum levels were determined in 45 pairs of MZ and 30 pairs of DZ twins. The quantitative evaluation concerned the different classes (IgG, IgA, IgM), subclasses (γG1, γG2, γG3, γG4) and types (k and λ), and was performed by the method of single radial diffusion.

The F ratio of variances between and within pairs is highly significant (0.001) for MZ twins, which are clearly concordant for high or low levels of all molecular classes. The comparison between and within pairs is also significant for DZ twins, albeit to a lower degree. Actually for H chains, the concordance is significantly higher for MZ than DZ. On the contrary, both kinds of twins are equally concordant for L chain levels.

The immunological nature of allergic diseases is a recognized fact, but their pathogenesis is still largely unknown, representing one of the less understood areas of immune pathology.

Twin studies in allergic diseases have been carried out before (Gedda and Teodori, 1962), contributing to prove the great importance of heredity in the occurrence of allergic disease.

Yet, the nature and mode of inheritance of allergic hereditary factors is still unknown, thus representing further question marks in the mystery of allergic pathogenesis.

The present study has been extended to include allergic diseases within the wider scope of total pathological experience, through a comparison between a sample of twin pairs with a history of allergic disease and a control sample of nonallergic twins.

All our data have been derived from the records of the Twin Register of the Mendel Institute. These records have been coded and transferred onto IBM punched cards with the support of the Italian National Research Council (Gedda and Milani-Comparetti, 1966). A population of 500 twin pairs was selected for having been included in the Twin Register before 1955, so as to have a minimum age of 15 years. The case histories of all these pairs had been coded and punched independently, according to a coding system developed in our Institute, which listed the following items: (1) oculorhinitis; (2) asthma; (3) urticaria; (4) allergic eczema; (5) unspecified allergic disease.

As many as 76 of our 500 pairs were found to have a positive history for at least one of these classes of disease, representing an incidence of 15.02% in our material.

Different forms of cardiovascular disease, including hypertension, give evidence that heredity is a predisposing factor. Yet, family and twin studies of blood pressure have consistently given inconclusive results. In earlier twin studies, Mathers et al (1961) and Osborne et al (1963) presented evidence that blood pressure liability rather than the measured levels of the blood pressure may constitute the critical manifestation of the genetic variable to be investigated.

A twin study has been conducted in which blood pressure measurements were obtained under basal conditions and following experimental stress. The results of this study and comparisons to the earlier studies will be presented.

During the past two decades prospective epidemiologic studies have established the association between several risk factors and coronary heart disease. Elevations of serum cholesterol and blood pressure, obesity, lack of physical activity and cigarette smoking are among the factors which have been related to an increased risk of heart disease. We are now entering a period in which vigorous efforts will be made to modify these factors in order to prevent the occurrence of heart disease. An important part of this effort will be to determine to what extent these factors are genetically controlled and to what extent they can be modified by manipulation of the individual environment. Recognizing this need, the Field Epidemiological Research Section, National Heart Institute, NIH, has recently embarked on a study of cardiovascular disease risk factors in a large sample of adult male twins. The purpose of the present report is to describe the protocol and methods to be used and the importance of this study to current research in cardiovascular disease.

It seems to be generally accepted that genetic factors take a place among the causes of coronary heart disease. Careful and extensive family studies, among others by workers in Carter's group, have shown that the risk to close relatives of patients with coronary heart disease is significantly increased. This may, however, be an effect of the common social background in families. Systematic twin investigations have been needed, which could distinguish between the effects of common environment and common genes, and allow an estimate of the relative importance of genetic and environmental factors.

The present study is an approach to this problem by using twins with coronary heart disease in the Danish Twin Register (Hauge et al, 1968). This was founded in 1954 and has been developed ever since. It now contains total medical information on about 10 000 unselected pairs of twins born in Denmark in the period 1870-1910, where both partners have survived the age of five. On January 1, 1968, coronary occlusion had been registered in a total of 352 twins.

Uchida and Rowe (1957), Lamy et al (1957), as well as Campbell (1961), were of the opinion that genetic factors do not play an important role in the genesis of congenital heart deformities. These authors could not find any concordantly affected pair among a total of 32 MZ twin pairs. Impressive family case reports and systematic investigations (Fuhrmann, 1970; Jörgensen, 1970) do not support this assumption. The results of twin investigations by Nora et al (1967) also contradict previous results. Among a total of 37 twin pairs these authors found 6/13 MZ and 1/24 DZ concordantly affected pairs.

Our own investigations began in autumn, 1966 and were recently completed. With the help of the registrar of birth offices and the cardiological team of the University of Göttingen (Prof. Dr. A. J. Beuren, Prof. Dr. H.-E. Hoffmeister, Prof. Dr. J. Koncz, Prof. Dr. J. Stoermer), we were able to find 50 index patients, each being a member of a twin pair, among 2427 propositi with different congenital heart defects.

Our own results are shown in Tab. I: 4/21 MZ (19.0 ± 8.6%) and 1/24 DZ (4.2 ± 4.1%) are concordantly affected. In five cases, the zygosity of the twins, as well as the diagnosis of respective cotwins, (stillborn or perinatal-dead) is unknown.

Genetic skin diseases have been considered with respect to their population and family frequencies, as well as to their concordance values, in MZ and DZ twin pairs. The clinical evolution of the disease has been further considered in its various stages and compared in MZ and DZ twins, concordant for the disease.

The material consisted of 100 twin pairs, with at least one member affected, subdivided with respect to concordance and zygosity. For each dermatosis, then, the population and family frequencies have been calculated. The following dermatoses could be studied: psoriasis, acne vulgaris, keratosis pilaris, alopecia areata, epidermolysis bullosa and dermatitis seborrheica.

A high concordance of clinical evolution in MZ twins has appeared to correspond to a low frequency of the disease, while a high frequency appears to correspond to low concordance values. This finding may be very useful for a better understanding of the disease's inheritance, as well as of its penetrance and expression.

It has been finally possible to evaluate the hereditary quantum vs. the environmental one in the determination of a dermatosis, by means of Holzinger's coefficient of heredity (H). The estimates of the latter vary from 35 to 50% in the various dermatoses examined.

L'enuresi primitiva (essenziale notturna) può essere definita come una minzione involontaria che avviene di notte durante il sonno, mentre nel corso della giornata la minzione è normalmente controllata, ed ha perciò caratteri peculiari.

Il notare, a volte, nei bambini affetti da enuresi primitiva la concomitanza di piccoli disturbi psichici o emozionali, di piccolo male, di stati di ipervagotonia o spasmofilia, conferma la natura funzionale complessa dell'affezione, sulla quale influiscono in prevalenza turbe della vita psichica o degli interessi affettivi del bambino. Alcuni dei fattori psichici implicati nell'enuresi (mancinismo, infantilismo nei giochi o discorsi, terrori notturni, fobie) possono anche essere considerati come indice di una incompleta maturazione psichica.

Non vogliamo qui discutere sull'etiopatogenesi della malattia, che è tuttora piuttosto oscura. La maggioranza degli autori considera l'enuresi primitiva come un disturbo funzionale complesso, non legato ad alterazioni dell'innervazione o della maturazione delle strutture nervose e muscolari preposte alla funzione vescicale, ma piuttosto riportabile ad alterazioni (o ritardo) del meccanismo volontario della minzione.

Si parla di enuresi primitiva quando il controllo anche notturno della minzione non è stato raggiunto entro i primi tre anni di vita. Secondo Harrison (1967), a 5 anni l'enuresi è presente nel 15% dei maschi e nel 10% delle femmine, a 9 anni nel 5%. Il disturbo cessa spontaneamente alla pubertà in quasi tutti i casi.

L'association entre hypertension artérielle essentielle et ulcère peptique a fait l'objet de nombreuses observations et études statistiques. La littérature indique aussi le pourcentage de cas où ces deux maladies sont associées. On peut notamment constater que la fréquence de cette association est — pour les sujets jeunes — moins forte qu'on ne le croyait jusqu'à présent (1.5%), tout en demeurant intéressante en raison du conditionnement neurogène des deux maladies.

Partant des données de la littérature, nous allons exposer les résultats d'une étude sur deux jumelles, qui permet d'illustrer l'association existant entre ces deux maladies de caractère génétique.

La justification de notre étude résulte des faits suivants:

1) La concordance de hypertension artérielle essentielle et ulcère peptique chez un couple de jumeaux MZ a été rarement, si non jamais, signalée;

2) Nous avons conduit une étude cherchant à approfondir le problème de cette association par un sondage des différents types de réactivité vasculaire et gastrique chez des jumeaux apparemment sains, mais provenant d'un père atteint des deux affections à la fois.

Notre étude a porté sur deux jumelles apparemment saines, âgées de 19 ans (K.M. et K.G.).

In the late 1950's and early 1960's, it became evident that some glaucoma patients developed elevations of intraocular pressure, which were difficult to control, following prolonged use of systemic or ocular medications containing corticosteroids (Chandler, 1955, Alfano, 1963; Armaly, 1963). In addition, some patients without glaucoma, when treated with steroids for long periods of time, developed clinical signs of chronic simple glaucoma (McLean, 1950; François, 1954; Covell, 1958; Linner, 1959; Goldman, 1962). Fortunately, the elevation of intraocular pressure was reversible if the drug was discontinued.

Over the past decade, extensive investigation of the “steroid response” has been undertaken. For this presentation, the steroid response may be considered as a gradual elevation of intraocular pressure, occurring over several weeks, in an eye being medicated with corticosteroid drops several times a day. The elevation in pressure is usually accompanied by a reduction in the facility of aqueous outflow. When relatively large numbers of subjects were tested with topical steroids, so that a wide range of responsiveness could be observed, a variation in individual sensitivity was demonstrated. Frequency distributions of intraocular pressure or change in pressure following steroids showed a skew toward the high side. On the basis of trimodal characteristics which they observed in such frequency distributions, Becker and Hahn (1964), Becker (1965) and Armaly (1965, 1966) considered the possible existence of several genetically determined subpopulations. These investigators distinguished three subpopulations on the basis of low, intermediate, and high levels of pressure response. It was hypothesized that these levels of response characterized three phenotypes, corresponding to the three possible genotypes of an allele pair, wherein one member of the pair determined a low level of response, and the other member determined a high level of response (Armaly, 1967).

The Authors report a 54-year-old male MZ twin pair with two single-born relatives suffering from glaucoma.

The twins are concordant as to glaucoma, but onset of the disease in the first-born occurred 20 years later than in the second-born. This high chronological difference is ascribed to the hardships the latter twin had suffered for three years in Africa.

The meaning of anticipation is discussed in the light of modern views on the time dimensions of the unit of inheritance (chronon).