Valvular heart disease is a multifactorial disorder. Twin studies may help to better understand both genetic and environmental determinants contributing to the development of valve lesions. We describe the case of a 45-year-old female asymptomatic triplet with multiple valvular heart lesions, with a somewhat different pattern between the dizygotic twin pairs compared with the monozygotic twin pair. After thorough assessment of medical history and physical examination, the triplet underwent two- and three-dimensional transthoracic and transesophageal echocardiographic examinations to assess the pathomechanism and severity of their heart valve lesions. The monozygotic twin pair (second-born twin B and third-born twin C) showed the same pattern of valvular lesions: mild mitral, tricuspidal, and aortic regurgitation of the same pathomechanism (posterior mitral valve cleft and aortosclerosis). Interestingly, the examination of first-born twin (twin A), who was dizygotic to twins B and C, revealed mild protosystolic mitral and mild tricuspidal regurgitation, but neither aortic insufficiency nor mitral cleft or indentation could be detected. Beyond the genetic effect, we presume that the intrauterine twinning process might also play a role in the development of congenital valvular heart disease. In order to verify this, further investigation should be performed on larger twin populations. Nevertheless, when one twin is affected, the other asymptomatic twin should also be examined for valvular heart disease.

We aimed to analyze the characteristics of development of relative weight in Japanese triplets from birth until 12 years of age. Data were collected through a mailed questionnaire sent to mothers of triplets asking for information recorded in medical records. Altogether we had information on 1,061 triplet children of 354 mothers born between 1978 and 2006. For these births, data on triplets’ height and weight growth, gestational age, sex, parity, and maternal age at delivery were obtained from records in the maternal and child health handbooks and records from the schools where children receive health check-ups. In addition, information on maternal height and weight was obtained. Triplets have a lower ponderal index at birth and lower body mass index (BMI) compared with the general population until 12 years of age, except for the period during 1 and 3 years of age. Moreover, birth weight had the strongest contribution to BMI of triplets until 6 years of age. After 9 years of age, maternal BMI was a significant factor affecting BMI of triplets.

Twin–twin transfusion syndrome (TTTS) is an antenatal complication of monochorionic multiple gestations. There have been few studies exploring the role of laser photocoagulation or outcomes following treatment in monochorionic triplet pregnancies with TTTS. We present a case where TTTS and twin anemia–polycythemia sequence (TAPS) complicated a monochorionic triplet pregnancy. Following the laser photocoagulation to treat the TTTS between the triplets, an intra-uterine death occurred in one triplet and TAPS developed in the remaining two triplets. Intervention in this case resulted in a 2-week prolongation of pregnancy and a positive outcome for the remaining fetuses. This case and other published data reviewed in this article suggest that laser photocoagulation has a potential role for TTTS in monochorionic triplet pregnancies.

We analyzed the characteristics associated with the growth in weight of Japanese triplets from birth to 12 years of age. The study included 376 mothers and their 1,128 triplet children, who were born between 1978 and 2006. Data were collected through a mailed questionnaire sent to the mothers asking for information recorded in medical records. For these births, data on triplets’ weight growth, gestational age, sex, parity, maternal age at delivery, maternal height, and maternal body mass index were obtained from records in the Maternal and Child Health Handbooks and records in the school where children receive health check-ups. The weight deficit of the triplets compared to the general population of Japan remained between 10% and 17% until 12 years of age. Moreover, at 12 years of age, the differences of weight between the general population and triplets were approximately –4.75 kg for boys and –6.00 kg for girls. Very low birth weight had the strongest contribution to body weight until 8 years of age. After 8 years of age, maternal body mass index was a significant factor affecting the weight of triplets until 12 years of age.

Birth weight in triplets is, on average, lower than in singletons and twins, and more children are classified as having very low or extremely low birth weight. Still, there is limited research on factors that affect triplet birth weight, and samples under study are often small. Chorionicity and zygosity influence triplet birth weight, but it is unknown whether the effect of zygosity can be entirely ascribed to the effect of chorionicity or whether zygosity has an additional effect on triplet birth weight. This question was investigated in 346 triplets (from 116 trios) registered with the Netherlands Twin Register for whom data on chorionicity were available. ‘Triplet’ refers to one child and the set of three triplets is referred to as ‘trio’. Trios and triplets were classified based on zygosity and chorionicity. With regression analysis, the effects of zygosity and chorionicity on triplet birth weight were examined, while controlling for gestational age, sex, and maternal smoking during pregnancy. In addition, within the dizygotic trios a within-family comparison was made between the birth weight of the triplets that were part of a monozygotic pair (with some pairs sharing a chorion), and the birth weight of the dizygotic triplet. Based on the classification on individual level, monozygotic, monochorionic triplets had a lower mean birth weight than dizygotic, dichorionic triplets. Most remarkably, in dizygotic trios, monozygotic pairs only had a lower mean birth weight than their dizygotic sibling triplet when the pair shared a chorion. We conclude that having shared a chorion, rather than being monozygotic, increases the risk of a low birth weight.

We analyzed the characteristics associated with the growth in length and height of Japanese triplets from birth to 6 years of age and present the growth charts for them. The study included 354 mothers and their 1,061 triplet children, who were born between 1978 and 2006. Data were collected through a mailed questionnaire sent to the mothers asking for information recorded in medical records. For these births, data on triplets' length and height growth, gestational age, sex, parity, and maternal age at delivery were obtained from records in the Maternal and Child Health Handbooks, which is provided by the authorities after a report of pregnancy. Birth length showed the strongest contribution to height of triplets from 1 to 6 years of age. In addition, birthweight was also a significant contributing factor to height from 1 to 3 years of age. Compared to the 50th percentile of the growth standard for the general population of Japan, the length and height deficit of the triplets was approximately 15% at birth (male, –7.0 cm; female, –7.0 cm), decreased within the first year of age, and fluctuated between 2 and 5% until 6 years of age (male, –3.7 cm; female, –3.3 cm). In conclusion, triplets have lower birth length and subsequent height than singletons. In spite of the catch-up growth during the first year of life, they are behind singletons even in mid-childhood. This study provides height growth curves for triplets.

We analyzed whether motor development in early life is different between singletons and triplets in Japan. The motor development was reported by mothers by postal questionnaire for 1,121 triplet children and in regular health check-ups for 13,906 singleton children. Children who were suspected of having neurological abnormality or disability were excluded from the analysis. The ages of milestone achievements were significantly higher in triplets for each outcome compared to singletons. Further, after adjustment for gestational age, birthweight, and birth length, the differences were significant for maintaining head, sitting alone and standing holding on. In children with birthweight of 2 kg or more, the ages of milestone achievements were significantly higher in triplets for each outcome compared to singletons, except walking holding on. Moreover, after adjustment for the confounding factors, the differences were significant for sitting alone and walking independently. On the contrary, singletons attained motor development facilitating crawling, walking holding on, and walking independently slower than triplets among those children with birthweight of 2 kg or less after adjustment for gestational age. In conclusion, triplets are overall at higher risk for the delay of gross motor milestones as compared to singletons independently of birth-related factors. In contrast, among children with a birthweight of less than 2 kg, singletons showed slower motor development than triplets after adjusting for gestational age. There is an obvious need to apply developmental standards that consider at least both multiple birth status (singleton, twin or triplet) and birthweight.

We analyzed the characteristics of weight growth and present the weight growth charts from birth to 6 years of age in Japanese triplets. The study included 366 mothers and their 1098 triplet children, who were born between 1978 and 2006. Data were collected through a mailed questionnaire sent to the mothers asking for information recorded in medical records. For these births, data on triplets' weight growth, gestational age, sex, parity, and maternal age at delivery were obtained from records in the Maternal and Child Health Handbooks, which is provided by the authorities after a report of pregnancy. Birthweight proved to be the strongest contribution on weight of triplets from 1 to 6 years of age. In addition, gestational age was also a significant contributing factor to weight from birth to 6 years of age. Moreover, males had a higher weight from birth to 6 years of age than females. Compared to the 50th percentile of the growth standard for the general population of Japan, the weight deficit of the triplets was more than 40% at birth (male, –1.28 kg; female, –1.28 kg), decreased within the first 1 year of age, and fluctuated between 4% and 9% until 6 years of age (male, –1.82 kg; female, –1.78 kg). In conclusion, triplets have lower birth weight than singletons and in spite of the rapid catch-up growth during first year of life they are behind singletons even in mid-childhood. This study provides growth curves for use in triplets.

We analyzed the characteristics associated with the growth in height of Japanese triplets from birth to 12 years of age. The study included 376 mothers and their 1,128 triplet children, who were born between 1978 and 2006. Data were collected through a mailed questionnaire sent to the mothers asking for information recorded in medical records. For these births, data on triplets' length and height growth, gestational age, sex, parity, maternal age at delivery, and maternal height were obtained from records in the Maternal and Child Health Handbooks and records in the school which children receive health check-ups. The height deficit of the triplets compared to the general population of Japan remained between 2% and 5% until 12 years of age. Moreover, at 12 years of age, the differences of height between the general population and triplets were approximately -3.6 cm for male and -4.4 cm for female. Maternal height showed the strongest contribution to height of triplets from 6 to 12 years of age. In conclusion, triplets remain shorter than singletons until 12 years of age.

Repeat-expansion mutations cause 13 autosomal dominant neurodegenerative disorders falling into three groups. Huntington's disease (HD), dentatorubral pallidoluysian atrophy (DRPLA), spinal and bulbar muscular atrophy (SBMA), and spinocerebellar ataxias (SCAs) types 1, 2, 3, 7 and 17 are each caused by a CAG repeat expansion that encodes polyglutamine. Convergent lines of evidence demonstrate that neurodegeneration in these diseases is a consequence of the neurotoxic effects of abnormally long stretches of glutamines. How polyglutamine induces neurodegeneration, and why neurodegeneration occurs in only select neuronal populations, remains a matter of intense investigation. SCA6 is caused by a CAG repeat expansion in CACNA1A, a gene that encodes a subunit of the P/Q-type calcium channel. The threshold length at which the repeat causes disease is much shorter than in the other polyglutamine diseases, and neurodegeneration may arise from expansion-induced change of function in the calcium channel. Huntington's disease-like 2 (HDL2) and SCAs 8, 10 and 12 are rare disorders in which the repeats (CAG, CTG or ATTCT) are not in protein-coding regions. Investigation into these diseases is still at an early stage, but it is now reasonable to hypothesise that the net effect of each expansion is to alter gene expression. The different pathogenic mechanisms in these three groups of diseases have important implications for the development of rational therapeutics.

Type 1 diabetes mellitus (IDDM) results from a chronic process of autoimmune destruction of ß cells of the Langerhans islets. The presence of autoantibodies (ICA, GADA, anti-IA2, IAA) in serum preceds the clinical onset of the disease. Genetic predisposition for IDDM is connected with HLA, CTLA-4 and insulin gene region.

The aim of the study was the genetic and immunological analysis of a triplet. One of them developed Type 1 diabetes mellitus. We analysed HLA class II, CTLA-4 and insulin gene polymorphisms in the whole family. Besides, we investigated immunological status of three brothers.

All patients present identical genotype for VNTR loci: D1S80, D17S5 and Apo B, as well as for HLA-DRB1, — DQA1, — DQB1, CTLA-4 gene and all studied insulin gene polymorphisms. That proves their monozigosity. The triplet presents strong genetic predisposition for IDDM. The two patients without overt diabetes have increased levels of ICA, GADA, IA2 and IAA.