The WHO Meeting of Investigators on Methodology of Twin Studies was held in Geneva from 24 October to 1 November 1965. The meeting was opened by Dr L. Verhoestraete, Director, Division of Health Protection and Promotion, who welcomed the participants. He said that this meeting of geneticists, epidemiologists and clinicians had been called to review the possible contribution of twin studies, a recognized tool in genetic research, to the broader field of epidemiological investigations, where so far they had found comparatively little use.

Professor D. D. Reid was elected Chairman; Professor L. Gedda, Vice-Chairman and Dr R. Cederlöf, Rapporteur.

Studies of general population characteristics include vital statistics such as mortality and morbidity data which are obtained on a routine basis. These data constitute one of the best sources of raw material for epidemiological studies and provide easily accessible information for basic research and for programme planning in control of disease. Very often they raise questions concerning the epidemiology of chronic disease, which may help delineate the relevant factors and provide guiding hypotheses for further research in this field. A deeper understanding of disease may also be arrived at through the study of individual characteristics in cross-sectional, retrospective and prospective studies, and through experimental investigations. A cross-sectional study can be used not only in determining prevalence of disease in a population, but it can also serve as the base-point for a longitudinal study of chronic diseases.

The study of the clinical material concerning the patients hospitalized at the Rome Forlanini Sanatorium during 25 years has indicated 894 patients of postprimary pulmonary tuberculosis, constituting 447 pairs of single-born brothers (♂♂ or ♂♀ or ♀♀).

The above pairs have been studied from the standpoint of their concordance with respect to the following three clinical parameters: (i) age of onset of postprimary tuberculosis; (ii) clinical form of the reinfection; (iii) pulmonary localization of the tubercular process. Such parameters were studied in the case of the brothers living together, as well as in the opposite case.

On the basis of the statistical analysis of the results, the AA. conclude for the existence of a tubercular predisposition in terms of a hereditary trait significantly influencing the course of postprimary tuberculosis with respect to both onset and localization, and especially to the clinical form. The clinical parameters appear to be more concordant, though in a statistically nonsignificant way, when the two affected brothers lived together.

The family and individual variability of the predisposition to pulmonary tuberculosis appears to be demonstrated. According to the AA., such predisposition would be inherited through a multifactorial mechanism.

The Authors show twin study to allow the determination of gene frequency and penetrance in the general population, by means of the analysis of distribution of phenotypic combinations in the twin pairs.

The AA. have studied the characteristical steps of the first and permanent dentition on 408 twin pairs (156 MZ and 252 DZ). These phenomena appear to be significantly genetically controlled. According to the AA., the hereditary units might possess a characteristic potential time span, which is a function of an energetic genetically conditioned charge. This parameter of the hereditary unit is called Chronon.

The Twin Clinical Method (Gedda, 1963) has been applied to the study of dental pathology. Four cases of MZ female twin pairs have been studied, concordantly affected by dental agenesis (case I), mirror-imaging dental agenesis (case II), diastema (case III), and dental caries and enamel dystrophy (case IV). The test has also been applied, and for the first time, to a set of MZ female triplets, concordantly affected by dental caries and malposition.

In all the above cases, the test has permitted to reject hypothesis of a concordance being due to chance, while postulating the existence of a causality.

The latter is ascribed to the common heredity characterizing MZ cotwins.

In order to test the possible effect of maternal inbreeding upon non-disjunction, ancestors of 104 children with Down's syndrome born to younger mothers were identified on the basis of official records. Among them, 6 had related parents, while 10 of the fathers and 12 of the mothers had also such parents. The relationship comprises first-cousins, first-cousins once removed, and second cousins. It was concluded that recessive genes are unlikely to be involved in the aetiology of non-disjunction of the 21st autosome, at least in younger mothers.

Alder's anomaly of the leucocytes, which had been considered as a manifestation of the gene-carrier of Fuchs' atrophia gyrata chorioideae et retinae, has not been found in other cases of the latter disease.

The Authors report on the steps involved in the computerization (coding of data, card punching and tape recording) of a Twin Register initiated in 1942 and currently approaching 11,000 cases of multiple births.

The Register is permanent in that it involves continued updating of information and addition of new cases. It includes twins of any age, sex, zygosity and health condition.

The experience gained in the reported project can be usefully shared in wiew of international cooperation and standardization.

During routine karyotypic analysis of patients with mental deficiency and congenital malformations, a partial deletion of the short arm of a B (4-5) chromosome was observed in two children (a male, 23 months old, and a female, 4 months old).

Clinical pictures and chromosomal abnormalities were found to be consistent with the findings in the « cri du chat » syndrome.

Scurvy, now regarded as a nutritional disorder due to the lack of the trace food constituent, vitamin C, is shown to be the end result of a typical genetic disease. This genetic disease syndrome has been named Hypoascorbemia. Its primary cause is the hereditary lack of — or defect in — the gene controlling the synthesis of the enzyme, L-gulonolactone oxidase. This is a mammalian liver enzyme, the last one in the series for converting glucose into ascorbic acid. Man is one of the few mammals that lacks this enzyme and hence is unable to sythesize his own ascorbic acid. The gene defect occurred during the course of evolution by a conditional lethal mutation. The replacement of the present vitamin C theory regarding the etiology of scurvy by this genetic concept gives important new viewpoints to the quantitative aspects of ascorbic acid in human physiology and also provides new rationales for the use of high levels of ascorbic acid in normal physiology and in the therapy of clinical entities other than scurvy.

Discordant schizophrenic monozygotic twin pairs were examined in order to clarify the view interpreting schizoid disorders as attenuated or incomplete expressions of schizophrenic heredity. The aggregate observations indicate that typical schizophrenia can be paired with all types and degrees of schizophrenic or schizoid illness, including clinical normality. These intra-pair combinations seem to occur more or less at random. The reviewed schizoid states showing evidence of schizophrenic psychopathology represent one of the developmental phases of schizophrenic process. Yet the psychopathologic connection with schizophrenia is not evident in all deviations and non-deviant personality patterns. Thus the seeming continuum of schizophnic psychosis — schizoid disorder — neurotic character — normal personality may consist of two discrete series: one with underlying schizophrenic psychopathology, and the other independent of the psychotic process. This division might reflect a threshold effect, dependent upon a switch mechanism.

The Authors studied the leukocyte alkaline phosphatase (LAP) activity in 40 subjects with Down's syndrome. The age of the patients ranged from one week to 15 years. Chromosome analysis was carried out in 13 cases. 42 normal children of the same age as the patients were used as controls. The mean value of LAP in the patients with Down's syndrome was 175.5 and in the control group 108.8. In the latter group the LAP activity was clearly influenced by the age; the highest values were obtained in children under 11 years of age. The regression coefficient of the LAP on the age in the control group was –3.73. In the patients with Down's syndrome the differences observed between the various age groups were not statistically significant.

Chromosome studies showed a 21 trisomy in 12 cases; in one case a 15/21 translocation was found. The latter case presented an elevated LAP activity.

The Authors support the hypothesis that the gene or genes controlling LAP activity are located in the 21 chromosome and that the LAP activity may vary under the influence of several factors within the limits of the genetic control.

Three familial cases of epibulbar dermoids, associated with lid ptosis, antimongoloid aspect of the palpebral fissure and nasal lobuloschisis are reported.

The hereditary character of this malformation is interpreted in terms of polimery.

When the result of the reaction to an antiserum is known for only one twin, it is nevertheless possible to calculate the probability that the twins be monozygotic, making allowance for that partial result.

The probability of monozygosity is calculated in the hypothesis of complete concordance.

This too high probability is then combined with the probability of concordance between sibs for the trait considered.

A case of two daughters of consanguineous parents, one with « pure gonadal dysgenesis », and the other with severe ovarian hypogenesis are reported. Both patients have positive nuclear pattern, and normal feminine karyotype, i e. 44 A + xx.

After reviewing the literature on familiar cases of « rudimentary gonads syndrome », the AA. suggest that the genetic mechanisms involved are different, according to the clinical picture and the chromosomal constitution.

In the few cases of classical Turner's syndrome with xo karyotype, a repetition of a chromosomal nondisjunction, during maternal or paternal gametogenesis, can be accepted. The cases of chromosomal mosaicism are probably related to an anomalous mitotic division of normal zygotes which takes place in the same woman, in the course of more than one pregnancy.

Various interpretations can be given to the cases of familiar pure gonadal dysgenesis. Since the patients show more often a normal feminine or masculine karyotype, the possibility that the anomaly is bound to an autosomal recessive gene has been suggested (see Hauser's case, 1960, in which, as well as in the one here reported, the parents were consanguineous).

Other possibilities are not to be underestimated: an early lesion of the gonads by environmental maternal factors, also in subjects with different genetic sex, should be taken into account.

A family with dysplasia spondylo-epiphysaria tarda is reported. This dysostosis clearly differs both clinically and genetically from Morquio's disease. The onset is at the age of ten or later. The skeleton deformation concerns mainly the vertebral column and lesser the thorax and pelvis. In the course of life the degeneration increases slowly. Eleven male members of this family were affected and out of these eight have been examined. An X-linked-recessive inheritance is suggested. The remarkable clinical and genetical analogy with the families described in the literature justifies the assumption that the dysplasia spondylo-epiphysaria tarda be an independent disease clearly differing from Morquio's one (Lamy and Maroteaux).

The Authors describe a pedigree including four certain and two probable cases of «Ehlers-Danlos syndrome ». All the affected subjects were born to consanguineous but apparently healthy parents. Of the three main symptoms of the syndrome, the patients presented hyperelasticity of the skin and hyperlaxity of the joints and of the ligaments, while the signs of cutaneous fragility were absent (« partial form » of E.-D. syndrome). In the first two cases it was possible to find some less common aspects of the E.-D. syndrome, such as ectasia of the trachea and of the main bronchi, anomalies regarding the eyes, the teeth and the nails, muscular hypotonia and hypotrophia, and particularly some skeletal manifestations (bending of the long bones, osteoporosis, anomalies of the methaphysis and epiphysis of the tubular bones, vertebral, thoracic and pelvic deformations).

The Authors emphasize the importance of these less common aspects of the E.-D. syndrome, and the similarity between these clinical signs and those found in other « heritable disorders of the connective tissue ».

The type of inheritance in this family (autosomal recessive) is discussed, in comparison to the commoner type (autosomal dominant) of inheritance of the E.-D. syndrome.

A new case has been presented of MZ twin girls, both showing albinism of the incomplete generalized type. Such cases are quite rare. Two elder siblings and the parents presented various degrees of diascleral translucency of the irides.

1. Sex-linked type of defective colour vision among 608 unrelated students, including 251 males and 357 females belonging to different communities residing in Madhya Pradesh of India, was investigated. Males were found to have 3.19% defective colour vision; again, of the defectives the deutans were found to be exactly three times greater than the protans. Significantly, none of the females was colourblind.

2. Brahmin of Madhya Pradesh displayed a comparatively low value of abnormal incidence being 2.88% among the other Brahmin samples. The occurrence of green-blind was found to be a little more than double of the red-blind in the sample, χ2 test for significance in respect of the total incidence of colour-blindness in various samples of Brahmin shows no heterogeneity (P>0.05). But, when certain Brahmin samples having a common origin are combined, some significant differences are brought out showing a clear statistical heterogeneity (P<0.02).