A research has been carried out on a sample of 29.309 Milan school children. Among them, 321 carriers of congenital aural fistula (FAC) have been found. Pedigrees could be drawn in 93 cases, covering three generations and including as collateral branches families of uncles and aunts. According to Smith's test (modified) the trait appears to be inherited as an autosomal dominant, with a penetrance of 85%. The phenotypical frequency (genetically controlled, i.e. excluding phenocopies) is of 1%, while the gene frequency may be estimated around 0.5%.

Though conception and reproduction have been favorite topics of the biologists of all ages many of the simplest facts of generation are still lacking their proper explanation. They remained mysteries and stimulated wild speculations not only among the uneducated people but also among the physicians, naturalists and others engaged in the scrutiny of Nature.

Fragile X syndrome is the most common cause of interited mental retardation in humans, with a frequency of approximately 1 in 1200 males and 1 in 2500 females [1]. It is second only to Down syndrome as a genetic cause of mental retardation, which has an overall frequency of 1 in 600. These frequency estimates suggest that fragile X syndrome accounts for approximately 3% of mental retardation in males, and perhaps as much as 20% in males with IQs between 30 and 55 [2]. The disease derives its name from the observation of a fragile site at Xq27.3 in cultured lymphocytes, fibroblasts and amniocytes [3].

The phenotype of the fragile X syndrome is mental retardation, usually with an IQ in the 4-70 range [4] and a number of dysmorphic features: long face, everted ears and large testicles [for review see ref. 5] (Fig. 1). Not every patient shows all the physical symptoms, which are generally more apparent after childhood. Macroorchidism is a common feature of fragile X syndrome in more than 90% of postpuberal males. Some patients show hyperactivity and attention deficits as well as avoidance behaviour similar to autism. Affected females generally have a less severe clinical presentation, and their IQ scores are generally higher, with typically borderline IQs or mild mental retardation.

No gross pathological abnormalities have been described in the brains of fragile X patients. Only a few post-mortem brain studies of fragile X males have been described and the information is very limited, presenting only non-specific findings such as brain atrophy, ventricular dilatation and pyramidal neurons with abnormal dendritic spines. It has been shown that the volume of the hippocampus was enlarged compared to controls [6], while a significantly decreased size of the posterior cerebellar vermis and increased size of the fourth ventricle was found [7]. Using magnetic resonance imaging it was shown that fragile X patients have an increased volume of the caudate nucleus [8]. The caudate volume is correlated with IQ and methylation status of the FMR1 gene.

Data obtained from 53 Panjabi Khatris families were tested for mode of inheritance of patterns on palmar interdigital area II. Gene frequencies were obtained from 1,000 unselected Panjabi Khatris.

Analysis of the data indicate that a single dominant gene, with approximately 88% penetrance, is responsible for D patterns in both the second and fourth interdigital areas of the palm.

A survey of chromosomal abnormalities has been carried out in Italy since 1966. Among the 1,551 subjects examined, the following abnormalities were found: 2 cases of C/C translocation, 1 of D/C, 5 of D/D, and 9 of D/G; 2 cases of Patau's syndrome with D trisomy; 4 cases of Edwards' syndrome; 176 cases of Down's syndrome, of which 163 with regular trisomy, 4 with mosaicism, 7 with D/G translocation, 1 with G/G translocation, and 1 with C/G translocation; 10 cases with 47,XXY complement; 1 case with 46,XY/47,XXY/48,XXXY mosaicism; 4 cases with 45,XO karyotype; 3 with 45,XO/46,XX, 1 with 45,XO/46,XY, 2 with 45,XO/46,XXr and 1 with 45,XO/46,XXi mosaicism; 2 cases with 47,XYY complement; 2 phenotypic females with 46, XY karyotype; and 5 leukaemic patients with Ph chromosome.

Furthermore, several kinds of normal variants were observed, such as no. 9 prominent secondary constriction, chromosome-D or -G enlarged short arm, 16-pair heteromorphism, Y-chromosome polymorphism, and satellited E chromosome.

A study of perinatal mortality in multiple pregnancy over a period of 12 years, 1972 to 1984, showed prematurity and low birthweight as the major causes of fetal loss. The highest risk was found at 28 to 30 weeks gestation (306/1,000). There was a significantly greater risk to babies delivered by the breech (136/1,000), and likewise in the second twin when compared with the first, ratio 1:1.4. A significant drop in the perinatal mortality rate, from 98/1,000 to 39/1,000, was observed between 1972-1978 and 1979-1984. Ultrasound has facilitated the earlier diagnosis of twins and provides more accurate serial fetal assessment. Bedrest, more vigilant antenatal care, intrapartum surveillance and improved neonatal care, are required to maintain and further reduce the perinatal mortality rate. When regional analgesia was employed in labour, the number of babies lost was 41/1,000, vs 93/1,000 in patients not receiving regional analgesia. External cephalic version and vertex delivery of the second twin is preferable to internal version and breech extraction. It should also be contemplated, as an alternative to elective cesarean section for a transverse lie or brrech presentation of the second fetus.

Twins deriving from a single zygote were produced in Triton alpestris and Triton taeniatus by two different series of experiments. The first type of experiments proceeded, by means of a glass thread put on and cutting through the median plane of early gastrulae, to a division of these into two lateral (right and left) halves. These halves may give rise to normally formed identical twins (fig. 2), or to twins with more or less accentuated deficiencies on their inner sides (figg. 3 and 4). In extreme cases they may even produce left or right half-embryos, or much reduced malformations with very imperfect organ formation. Generally considered, the regolation in the head region is better than that in the tail one, and much better than in the trunk. Most of the heads show two eyes of equal size and normal position; in rare cases we encounter two eyes of different size, or synophthalmus or cyclopia. The «real» half-embryos have only one laterally situated eye (tab. 2). The normally formed identical twins deriving from half an egg each, develop into properly proportionned embryos of half the normal size; the resulting larvae reach the normal size of the equally-aged control larvae deriving from entire eggs, often before the stage of nourishment, (fig. 5, tab. 3).

In the second series of experiments, an early gastrula was cut through in correspondence to the median plane, and then the complete presumptive epidermis of another gastrula and, respectively, of a third one, was stuck on to the wound surfaces of the halves in normal orientation (fig. 6). The right and the left combinations resulting therefrom give rise, in the original median line, to long, narrow and apparently somewhat too great neural plates, the external half-portion of which was fournished by the host half-gastrula and is somewhat more strongly developped than the inner half-portion deriving from the presumptive epidermis (fig. 7 a, b). This epidermis that was stuck on to the gastrula-halves' surfaces, takes part in the formation of the embryos either totally or at least for its greatest part. No perfect larvae will be formed (tab. 4). The head is always bilaterally developped, but it is often asymmetric and shows synophthalmous or cyclopic character (figg. 8, 9, 10, tab. 5). The trunk is sometimes normal (fig. 8 a), but it may also show an axial system of too great length (fig. 8 b), or dorsal deficiencies—often in the form of either symmetrical or asymmetrical Spina bifida—with dorsal incurvation (fig. 9 a, b). The tail can be either normal, or crooked, or defective, or doubled. In the best cases we see, in the first series of experiments, the regolation of the half-organiser of the gastrula-half into an entire organiser of half the normal size, while, in the second series of experiments, the regolation can produce an approximately normally sized entire organiser, which however, in the anterior head region is lacking of its full indutcive capacity.

In both series of experiments the right hand member of the twins was observed to show inversion of the situs viscerum.

Early detection is a prerequisite for the active management of twin pregnancy. Detection rate was not, or was only slightly, increased by improved anamnesis or more alert physical examination. General placental lactogen screening selected 95% of the twins but implied a subsequent ultrasonic screening examination of 16% of the pregnant population for the definitive diagnosis. A general screening programme with ultrasound detected 90% of the twin pregnancies (methodological error 1.7%; not participating 8%) in the mid-trimester. Extensive restriction of maternal physical activity from the 29th to the 36th gestational week by bed rest in hospital reduced perinatal mortality to the level of singletons and also decreased the incidence of neurological and mental handicap among the surviving twins. For the supervision of twin pregnancy, urinary estriol estimates predict birth weight rather than fetal distress. Monitoring with repeated ultrasonic biparietal diameter measurements seem limited in value; even large intertwin BPD differences are not indicators of fetal distress in the smallest twin. The decrease of perinatal mortality and morbidity among twins subjected to special antenatal supervision suggests that large gains can be made by early detection and antenatal hospitalization. The earlier finding that impairment of the intrauterine supply line is closely associated with neurological sequelae gives added importance to the reduction of CNS handicap and of growth-retarded fetuses observed during such a programme.

The annual variation of the sex ratio (SR) of 1385 twin births was analyzed and compared to that of 85909 singletons. These births referred not only to live births but also to stillbirths in two southeastern Brazilian maternity hospitals from 1984 to 1993. While the annual variation of the SR of singletons was very small, that of twin births was extremely high, due to the significant heterogeneity of the annual data. It is suggested that the large SR annual variation of the twin birth might be a consequence of the variation of male or female monozygotic twins.The hypothesis that twin births show a lower sex ratio than singletons could not be supported by the present data.

Report of the result of familial examinations on 49 stillborn of before half year of life died and dissected children with lethal anomalies.

1. In two of 4 families, whose probands suffered from harelip and clett palate combined with other deformities, is supposed, that—just like harelip and clett palate without other malformations—an unstable dominant gen being origin of the mistake of development.

In one case with a special severe combination and probable consanguinity of the parents is to think of homozygoty.

In a fourth case the question of the origin of the combined deformities by « psychical trauma » may be discussed.

2. In 32 families the cause of death of the probands is to be seen in a lethal closing mistake of the vetebral column.

a) In seven of 20 families with an anencephalus signs of « Dysraphies » and other anomalies were found which may be caused by pathological gens. One time both parents of a (homozygote?) anencephalus who showed deformities of heart and limbs had Spina bifida occulta.

b) In 5 of 12 families with Spina bifida aperta was the cause of deformation an unstable unregular dominant gen. In two other families is this probable.

Anencephalie and Spina bifida aperta may be found together in the same family. Heterogenie ist probable for both.

3. a) Hydrocephalie without other deformities was in 8 families not inherited.

b) 4 families with microcephaly showed differences. Dominant gens for « Dysraphies » and recessive gens may bring about microcephaly.

c) Consanguinity of the parents in a case of cyklopy is seen to be sign of recessive inheritance.

A kindred is described with a probably new inherited syndrome, involving bilateral congenital hip dysplasia with coxa vara, patella aplasia and tarsal synostosis. This association is probably inherited as an incomplete dominant trait, apparently as a result of a new mutation.

In this case a single pleiotropic gene might be held responsible for the multiple skeletal defects.

From a bibliographical review, it may be concluded that the nosological association of these multiple defects has never been published so far.

The negative influence of some insecticides on male fertility has been noted. We report our cytogenetic observations on a group of infertile insecticide workers. Increased chromosomal breakage was a constant finding and the Y chromosome was especially damaged. This may account for impaired spermatogenesis. Furthermore, the involvement of heterochromatic chromosomal variants both in the individual susceptibility to the chemically induced damage and in the reproductive fitness is emphasized.

The heredity investigation on thrombopathia (v. Willebrand-Jürgens) at Aaland-Is. revealed the autosome-dominant inheritance of this blood disorder. Until now, it has been possible to keep watch on thrombopathia for five generations. The penetration of the thrombopathia gene is high, the expressiveness is unsteady. The bleeding tendency occurs in both sexes. On a number of patients, recent investigations have shown, that there can be a certain deficiency of factor VIII (AHG) as well as the functional disorder of thrombocytes. The role of factor VIII deficiency in the pathogenesis of thrombopathia (v. Willerand-Jürgens) is not clear yet. Recent investigations on patients with aalandish throm-bopathia have shown certain morphalogical changes in thrombocytes, not existing in thrombocytes of healthy persons.

Two factors emerged from a search for obstetric phenomena that might explain concordance of leukemia in both members of a twin pair within days or months of each other: antenatal exposure to ionizing radiation; and antenatal cojoined intrauterine circulation. In addition, antenatal tumor metastasis and chromosomal changes, antenatal or postnatal, may be contributory. Continued observation of reports should be carried out.

The Strong Vocational Blank inventory was administered to 43 pairs of identical and 34 pairs of fraternal twins in high schools in the Metropolitan Detroit area, and scores obtained on 44 vocational preference scales and 3 personality scales. F tests of the ratio between fraternal and identical within twin pair variances were significant beyond the .01 level of significance for the scales for Physicist, Mathematician and Osteopath while 9 more scales had F-ratios significant beyond the .05 level; these were for the scales of Dentist, Personnel Director, Veterinarian, Sales Manager, Aviator, Chemist, Public Administrator, Engineer and for the scale of Interest Maturity. Thus a total of 12 scales had F-ratios indicative of some hereditary contribution to the within pair variance of the twins in this study.

A comparison with the results published by Carter in 1932 was possible for 21 scales, by computing intraclass correlations for the present data. From these, as well as from the intraclass correlations reported by Carter, h2 values were computed and compared. There was stronger evidence for hereditary components in the earlier study, and the rank order correlation for the h2 values in the two studies was only .16, although in both studies it was found that the “Science” group of interest scales had the highest “average” h2 value (computed from average intraclass correlations, after Z-transformation).

These results are interpreted as indicative of a small but persistent contribution of hereditary components to the vocational choices reflected in scores on the Strong Vocational Preference Blank, particularly for scientific careers.

The use of the male form for the female twins in this study seems partly justified by the presence of equally often high mean values on scales and higher heritability estimates on some scales compared with the boys.

Multiple birth rates in entire Japan were analyzed using vital statistics for 1951 to 1988. The triplet rate was nearly constant from 1951 to 1974, where the rate per million births was 58, then increased with the year up to 1982 (104), and decreased up to 1984, and suddenly increased thereafter (109 in 1987). The average rate of quadruplets per million births from 1951 to 1968 was 0.93, then increased with the year up to 1975 (7.5), and decreased until 1984 and suddenly increased thereafter (10.6 in 1987). The rate of quintuplets was 0.77 per million births during the period from 1975 to 1987. The higher multiple birth rate since 1975 was attributed to the higher proportion of mothers treated with ovulation-inducing hormones in Japan. Since 1985, higher multiple birth rates might be partially attributed to in vitro fertilization. The stillbirth rates for male triplets gradually decreased from 1960 to 1978 and thereafter remained constant at a little higher level except in 1988, whereas the rates for females gradually decreased with the year. The overall stillbirth rates decreased to 1/4 for triplets and to 1/5 for quadruplets during the 37-year period from 1951. The overall stillbirth rate of quintuplets was 0.60 (51/85) during the period 1975-1987.

The authors describe a new hereditary dystrophy of the cornea, the specked heredo-dystrophy of the corneal parenchyma. In the corneal stroma of both eyes speckles can be easily distinguished; they are more or less numerous and can be found in all the layers of the parenchyma, as well in the center as at the periphery. Dimension, shape and density of the speckles are very variable: they are oval, round or festooned; some of them are opaque at the borders; others show a more diffuse trouble; others are dotted; their borders are well-cut, regular or indented. In optical section the opacities are thin and flat. This dystrophy is not evolutive and is transmitted as an autosomal regular dominant trait. One member of the affected family shows a cloudy central dystrophy of the corneal stroma, so that it is possible that there exists a relationship between these two affections.

In their general model of twin concordance Allen and Hrubec recently introduced the concept of secondary ascertainment rate to consider partial ascertainment of secondary cases. This concept is found to be of limited interest because only pairs where valid information can be obtained from both twins should be included in genetic analyses. It is furthermore shown that the validity of the proband method and the Allen/Hrubec model depends on the equivalence of ascertainment in twins from concordant and discordant pairs. However, if this condition is fulfilled, it has been shown how the ascertainment probability in cotwins of probands is related to the overall ascertainment probability in the total twin population.

The term gestational trophoblastic disease is used to indicate a group of both benign and malignant trophoblast, including molar degeneration of villi, hydatid mole, invasive mole and choriocarcinoma.

This study shows a new classification of trophoblastic disease existing with a living fetus or fetuses. Benign hydatid mole is the initial stage of the disease continuum, whereas highly malignant choriocarcinoma is the final stage of this spectrum.

The twinning, triplet and quadruplet rates were found to be 23.8, 0.3 and 0.04 per thousand maternities, respectively in a survey of 71,773 maternities carried out in Ibadan and Igbo Ora, Nigeria. This represents a dramatic fall from the rates found in previous studies. The findings are discussed in the light of changing dietary habits.