Report of 4 families with two or three sibblings who suffered from different malformations of skeleton system and dwarfism.

In the first family is supposed, that the different severe chondrodysplasie of three children who descended from healthy parents was caused by a recessive gen which is unstable in manifestation.

In the second family was found that a dwarfic mother had two sons with phenotypical differences on chondrodysplasie.

In the third family a sister who was less deformed and a brother with severe dwarfism (among 13 sibblings) showed different phenotypes of a rare (skeleton) system sickness in any way related to chondrodysplasie. Consanguinity of their parents seems to be expression of a single recessive gen.

In the fourth family were found two brothers who had healthy, blood related parents. The abnormities of their skeleton system are supposed to be a rare form of dysostotic dwarfism.

The observations above communicated may show how many special gens exist in pathological human genetics. The phenotypical differences of special human deformities seem to prove a dependence from a respective genotypical association.

The complex serologic behavior of the Rh-Hr agglutinogens has been underlined by the recent discovery that, with very rare exceptions, associated with blood factor Rh0 of Rh-positive blood, there are numerous other blood factors which we designated RhA, RhB, RhC. Rare Rh-positive individuals exist whose bloods have blood factor Rh0 but lack one or more of the other components. Such individuals can and have become sensitized to the missing blood factor. For example, in the case of an Rh-positive individual lacking blood factor RhA, anti-RhA may be produced. So, too, when RhB and RhC, are lacking, anti-RhB or anti-RhC may be produced. In fact, all 3 have been identified. The resulting anti-RhA, anti-RhB and anti-RhC serums are indistinguishable from “standard” anti-Rh0 serum in parallel tests on a random series of blood specimens, unless the series happens to include one of the rare Rh-positive bloods lacking blood factor RhA (type Rh0a or type Rh1a, etc.).

In the present paper, anti-RhA serum from a sensitized type Rh1a mother whose child had erythroblastosis was used for studies on the distribution and heredity of the RhA blood factor. In addition, attention is called to the fact that Unger and Wiener have identified anti-RhB and anti-RhC although they are reporting at this time their studies with anti-RhA. A total of 2012 blood specimens from Rh0-positive individuals were tested; 951 from Caucasoids and 918 from Negroids. In tests on blood from Caucasoids, a “standard” Rh0 blood factor was invariably associated with a “standard” RhA blood factor. In no instance where the reactions with anti-Rh0 serums were typical was the RhA factor absent or a variant. However, if the Rh0 factor was a variant, 3 possibilities with regard to factor RhA were identified. Either factor RhA was “standard”, or factor RhA was a variant, or factor RhA was absent. This last possibility rarely occurs in Caucasoids since in our series only 1 Caucasoid blood or 0.1 percent lacked RhA blood factor and in that case the Rh0 factor was a variant.

Among the 918 Rh-positive blood specimens from Negroids examined the situation was found to be somewhat different. While a “standard” Rh0, was almost always associated with a “standard” RhA, in 0.9 percent the RhA factor was absent. Among bloods with a Rh0 variant blood factor, just as with Caucasoids, all 3 possibilities were identified, namely bloods with “standard” RhA, with RhA variant, and also bloods with blood factor RhA absent. The incidence of Rh-positive bloods lacking factor RhA was considerably higher among Negroids than among Caucasoids, namely, 1.6 percent in Negroids, as compared with only 0.1 percent in Caucasoids.

One interesting family was studied. The father's blood had the “standard” Rh0 blood factor, but lacked the RhA component (type Rh0a). The mother's blood had the Rh0 variant blood factor, and also lacked blood factor RhA (type ). The child's blood was of the same type as its mother, namely, Rh0 variant and lacking blood factor RhA (type ). The possible genetic explanations for these observations and their clinical significance were discussed.

A total of 198 pairs of monozygotic twins reared apart and together were surveyed on their lifestyle and blood pressure through mailed questionnaires. The age of the subjects ranged from 47 to 87 years. The intrapair concordance rate on blood pressure increased from 51% (age of separation 0-5) to 78% (age of separation 26 and over) as the age of separation advanced. The concordance rate on occupation was 59% at the age of separation 0-5 and 87% at the age of separation 26 and over. The intrapair concordance on the food intake (egg, meat, fish, milk and salty seasoning) was positively correlated with the age of separation. Hayshi's quantification theory III (multivariate analysis) was used to claryfy the lifestyle pattern in 39 MZ pairs discordant on blood pressure. There were three factors (meat, milk and occupation) which were closely related with each other in the “non-hypertensive” twins, while lifestyle were not patterned in the “hypertensive” twins. The concordance rate of these three items increased along with the rise of concordance rate of blood pressure as the age of separation advanced.

Twin births are known to vary across seasons in several countries. It has been hypothesized that this variation may be due to seasonal changes in luminosity leading to pineal gland-mediated multiovulation among susceptible mothers. To describe seasonal variation of twin births in Washington State, all mothers residing in Washington State who gave birth to both a pair of twins and a singleton baby between 1984-1990 (n = 1168) were identified through linkage of computerized State birth certificates. Using a “matched-on-mother” case-control design, the estimated month of conception of twin gestations (the “case” events) were compared to that for their singleton siblings (the “control” events) to determine their relative occurrence during periods of high vs low sunlight in accordance with local climatological data. For the study population as a whole, there was only a slight tendency for twins to have been conceived during the period of high sunlight compared to their singleton siblings (OR = 1.3, 95% C.I. = 1.0-1.7). When stratified by concordant-sex vs discordant-sex, however, more discordant-sex twin pairs were conceived during the light period than corresponding singletons (OR = 1.7, 95% C.I. = 1.0-2.8), whereas no association was found for concordant-sex twins (OR =1.1, 95% C.I. =0.8-1.6). The presence of an association only among discordant-sex twins, all of whom are dizygotic, is consistent with the hypothesis that exposure to sunlight may stimulate multiple ovulation, and thus increase the incidence of twin gestations among twin-prone mothers.

Fucosidosis is an autosomal recessive disorder caused by a deficiency of alpha-L-fucosidase. Up to now 79 cases have been described and several others identified but not yet published. The higher incidence of the disease is in Italy, where nearly 20 patients have been identified. Fourteen disease-causing mutations have been detected and four of them, Q422X, G60D, E375X, P141fs are present in more than 70% of the forty patients studied. In Italian patients, only seven mutations have been described and P141fs and G60D mutations are present in more than 50% of the cases. The P141fs mutation is absent in other ethnic groups. It has been impossible to establish genotype-phenotype correlation so far and the clinical variability of the disease cannot be explained only by genetic heterogeneity.

The symbols for trie 4 allelic M-N-S genes in common use, namely, MS, Ms, NS, and Ns, are satisfactory only if one subscribes to the theory of linked gene couplets, but not for those who, like the present author, believe that the theory of multiple alleles is valid. Therefore, it is proposed to designate the 4 allelic genes by the symbols Ls, L ls and l, respectively. These symbols are easy to learn and to use, if one bears in mind that L stands for the presence of blood factor M in the corresponding agglutinogen, and l for the presence of blood factor N. Similarly the letter S in the superscript stands for the presence of blood factor S in the corresponding agglutinogen, while the absence of any superscript denotes the presence of blood factor s. It is unnecessary to change the names of the phenotypes. This is fortunate, since duplication of nomenclature is avoided, such as exists unnecessarily in the case of the Rh-Hr types. The purpose of a phenotype name is to identify and not to provide a full description, or to indicate the genetic mechanism. For this reason, the phenotype designations of the M-N-S types should be the same, regardless of the genetic theory to which one subscribes.

The practicability of the new gene symbols for the M-N-S types is demonstrated by applying them to a sample mating. A simple method of estimating the frequencies of the 4 allelic M-N-S genes is also described. These formulae are applied to Boyd's data on the distribution of the M-N-S types among 230 Bengalis. The results obtained do not differ significantly from those obtained by the more complex maximum likelihood method. Since the maximum likelihood method does not improve the accuracy of the estimates, the additional effort and skill which is required are wasted. The simple formulae proposed here yield results which fulfill all the requirements of anthropologists and geneticists.

The incidence of twinning in India, as estimated on the basis of data from the various types of maternity centers, so as to include both urban and rural population, appears to be 15.97 per thousand (12.6 DZ, 3.3 MZ). The incidence is significantly higher in rural than urban populations (18.1 vs. 11.8 per thousand). It is suggested that this may be accompanied with a higher production of DZ, possibly opposite-sexed twins.

Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder with extensive clinical variability. Present estimates of the prevalence of TSC suggest that it may exceed 1:6,000. New mutations are frequent, as about 2/3 of all cases are apparently sporadic. Locus heterogeneity has been established, with one gene on chromosome 9q34 (TSC1) and the other on chromosome 16p13.3 (TSC2). The majority of TSC2 mutations are propably subtle alterations. In some cases, somatic and germline mosaicism might be explanations for intrafamilial phenotypic variation and apparent non penetrance. A role of the predicted protein product tuberin in growth suppression would be in agreement with allelic losses observed in tumors of TSC patients. Studies on tuberin using antibodies raised against various parts of the protein can be expected to provide insight into its normal and impaired function.

The results of pilot studies of the activities of platelet monoamine oxidase (MAO) and catechol-0-methyl transferase (COMT) in the blood of selected schizophrenics and the families of schizophrenics is presented.

No statistically significant difference was found between the blood COMT levels of 21 control subjects and 26 schizophrenics, whereas the values found for platelet MAO activity were significantly lower for the schizophrenic group than for the control group.

In one acutely disturbed first-admission schizophrenic the platelet MAO activity increased to a normal level in parallel with the clinical improvement, whereas in the relapsing schizophrenics the platelet MAO activity remained at its initial level although the clinical picture improved. No consistent findings with regard to the platelet MAO activity emerged from the study of 3 families having a history of schizophrenia.

Another family in the Åland archipelago (Fennoscandia) suffering from a hemorrhagic disorder (von Willebrand-Jürgens' disease, heredi tary constitutional thrombopathie) is described. This family, so far the largest in the literature, has many common ancestors with the original bleeder families on Åland described in 1926 by v. Willebrand. Of the more than 1300 kindred traced genealogically, 132 (71 women and 61 men) in the five most recent generations have had manifest bleeding disorders in their medical history. Of the ca. 450 living relatives of this family 211 could be examined, and of these 56 females and 50 males were confirmed to be bleeders anamnestically, clinically or, and hematologically. Several cases were analysed exhaustively by modern coagulation tests. The clinical and laboratory hemostatic findings varied widely both inter- and intra-individually. Some patients showed a partial lack of a plasma factor (AHG) coupled with a qualitative platelet defect. Other patients of this family without bleeding disorders had a markedly prolonged bleeding time. The vascular disturbances also vary widely. The consanguinity in this pedigree is unusually high. The autosomal recessive in heritance are discussed. According to the mendelian segregation ratio, a not sex-linked, dominant transmission of the hemmorrhagic diathesis was in question. I has been possible to observe the hemostatic disturbances in 4-5 generations. The penetration of the gene is high, the expressiveness is unsteady.

The A. has studied 51 pairs of epileptic twins: 20 were MZ (11 ♂, 9 ♀) and 31 DZ (9 ♂ 12 ♀, ♂♀).

An ereditary aetiology has been found in 65% of cases:

a) by the concordance of 80% of MZ against 35% of DZ. The MZ concordant in the symptomatic form were 62,5% the DZ 14, 5% the MZ concordant in the so-called idiopathic form were 91%, the DZ 50%.

b) by the incidence in one third of the families of a relative with epileptic seizures (3-4,7% against the 0,5% of general population).

Genic information is not specific either for the convulsive form nor for the electroencephalografic dysrythmia which are only some of the phenotypic manifestations of a deeper disturbance. The pathologic gene or genes should act at a metabolic level with a pleiotropic action upon more functions of the nervous system. The genetic action of the major gene is that of an autosomic, dominant one.

The effect of migration on pairwise concordance for disease was assessed in 11,154 twin pairs of the Finnish Twin Cohort Study by comparing the pairs living in the same province to the pairs which members were living in different provinces of Finland. The cumulative incidence of psychosis and hypertension for the years 1972-1985 were analyzed. The cumulative concordance of psychosis for those MZ twin pairs living in the same province were higher than for those MZ pairs living further apart. Similar findings were found among DZ pairs for psychosis. The cumulative concordance of hypertension was only slightly higher among those MZ and DZ pairs living in the same province compared with pairs living in different provinces. These results indicate an overestimation of concordance of psychosis caused by selective migration. This bias in twin studies is likely to influence heritability estimates in a sample of limited geographical area.

During a 10-year period (1971-1980) 16 sets of conjoined twins were delivered in the author's hospital. The incidence of those twins was 1 in 4242 deliveries, 1 in 69 multiple births, and 1 in 139 congenitally malformed babies. All diagnoses were made during labour or at operation and all babies were lost. There were no maternal deaths.

A total of 88 women with a twin pregnancy who had elective cervical suture were compared with 76 women with a twin pregnancy who had cervical assessment between the 13th and the 28th weeks of gestation but received no active treatment. The incidence of spontaneous onset of labour before 36 weeks was higher in the cervical suture group, and 53.4% of them sustained cervical damage.

The rate of infant mortality of triplet individuals (deaths under one year of age) was computed using 34 sets of triplets born in the first half of 1974. The rates were 8.82%, 9.68%, and 10.34% for the first-, second-, and the third-born triplets, respectively. For males and females the rates were 8.33% and 10.34%, respectively, and the difference was not significant. The rate decreased with gestational age up to 32-35 weeks. For those with heavier weight at birth (≤2,000 g) the rate was lower (0%) than for those with lighter weight (<2,000 g, 8.16%), but the difference is not significant (P = 0.087). Infant mortality rate of triplets decreased with increased monthly expenditure of the household.

Fifty marriages of twins to twins have been studied. Most of them have the characteristics of MZ twins. All have an identical outcome of their marriages within each set. This finding and others from the literature are consistent with the idea that marital stability depends in part upon one's original “blueprint” for physical and emotional health.

Two findings in this study, and others from the literature, are consistent with the idea that similarities at the chemical level may in general tend to promote a better understanding of each other and hence more congenial relationships: (a) all but one of the twin foursomes have lived closeby; three-quarters of them share the same house, even after they have had children; and (b) there is some degree of similarity in the ABO and Rh blood groups between husbands and wives in this sample.

The stably-married twins knew each other for an average of four years before marriage, whereas the divorced and annulled ones met only a few weeks or months before marriage.

Four hundred and thirty four twins occurring in 220 women were studied during a period of 11 years (1969–1979) at Notre-Dame Hospital.

Perinatal mortality (< 28 days) was compared before and after 1974, and the impact of ultrasound technique upon perinatal outcome was assessed during the second period (1974–1979). The main factor associated with perinatal mortality was low birth weight caused by either prematurity or intrauterine growth retardation.

While fetal mortality remained unchanged within the two study periods, neonatal mortality decreased from 68.2/1,000 to 28.9/1,000 mainly due to increased survival rate of twins below 1,500 g at birth.

With identical perinatal care during the same period, perinatal mortality and incidence of intrauterine growth-retarded twins remained unchanged despite early diagnosis by ultrasound.

We described a D1 trisomy syndrome patient who had a normal 46,XX cell line and 15.4% of lymphocytes with a 47,XX,+D chromosome constitution as an occasion to review normal trisomy 13 mosaicism.

A case report is given of a pair of monozygotic twin girls with neurofibromatosis caused by a new mutation. The symptomatology was dominated by a neurofibrosarcoma on the leg of one twin and by a large plexiform neurofibroma on the neck of the other twin. Otherwise, the disease showed similar, although not identical or mirror-image distribution of subcutaneous neurofibromas and café-au-lait spots. The twins had identical HLA and blood group antigens and the same chromosome aberration. These case reports indicate that nonhereditary factors may influence the manifestations of neurofibromatosis. A review of the literature on monozygotic twins with neurofibromatosis is given.

Limited data suggest that cesarean section (CS) may be the preferred method of delivery for triplets. Despite this, it is also felt that the third triplet is at great risk at delivery. We reviewed our experience of 14 triplet pregnancies at Northwestern University between 1981 and 1985. All deliveries were attended by neonatal teams in sufficient number to resuscitate each infant. Of the 14 pregnancies, two ended in previable loss. Thirty-six infants were born from 12 pregnancies of a mean gestational age of 33 weeks (28-38 weeks). The overall survival was 97.3%. Two women delivered vaginally. While the first was successful, the second resulted in vaginal delivery of the first two triplets followed by emergency CS for the third. That infant had a cord blood pH of 6.96(BE-19), was resuscitated and survived. All 10 CS were successful. The mean cord blood gas tensions and pH were normal. In addition, Apgar scores, the requirement for mechanical ventilation or supplemental oxygen, and mortality did not differ between the first and thirdborn triplet. These observations suggest that CS was beneficial. Our very low mortality rate supports the concept that CS delivery and aggressive neonatal resuscitation and therapy greatly enhances survival.