Search

Introduction: One of the leading causes of infant blindness is cataracts. The prevalence of congenital cataracts has been estimated to range between 1 and 15 per 10.000 children globally. Congenital cataract in twin babies is a rare case. This case will report the outcome of comprehensive management of congenital cataracts in dizygotic twin babies. Case presentation: Eight months old dizygotic twin babies came to our clinic with the primary complaint of whitish appearance in the pupil of both eyes since birth. They were born a term with cesarean delivery, and the birth weight was 2.700 g and 3.100 g, and they were the fourth and fifth children in the family. There is no family history of congenital cataracts. The visual acuity of both eyes was a response to light and had blink reflex positive. The cataract was bilaterally and dense on both babies. Fundus reflex and Torch examination were negative. Ultrasonography (USG) of the retina was standard on both babies. Discussion and conclusions: Isolated congenital cataract in twin babies is an unusual condition that should be treated comprehensively. Congenital cataracts cause deprivation amblyopia, refractive amblyopia, and permanent vision impairment, and the early diagnosis and quick treatment, such as surgical timing and visual rehabilitation, are critical to successful management. A case of isolated bilateral cataracts in dizygotic twin infants is presented here. Comprehensive care is required to monitor the visual result of cataract surgery. It is unusual to find an isolated congenital cataract in dizygotic twin infants. Early diagnostic and comprehensive management should be done early to maximize the visual outcome.

Objective To investigate differences in the heritability of skeletodental characteristics between twin pairs with skeletal Class I and Class II malocclusions. Methods Forty Korean adult twin pairs were divided into Class I (C-I) group (0° ≤ angle between point A, nasion, and point B [ANB]) ≤ 4°; mean age, 40.7 years) and Class II (C-II) group (ANB > 4°; mean age, 43.0 years). Each group comprised 14 monozygotic and 6 dizygotic twin pairs. Thirty-three cephalometric variables were measured using lateral cephalograms and were categorized as the anteroposterior, vertical, dental, mandible, and cranial base characteristics. The ACE model was used to calculate heritability (A > 0.7, high heritability). Thereafter, principal component analysis (PCA) was performed. Results Twin pairs in C-I group exhibited high heritability values in the facial anteroposterior characteristics, inclination of the maxillary and mandibular incisors, mandibular body length, and cranial base angles. Twin pairs in C-II group showed high heritability values in vertical facial height, ramus height, effective mandibular length, and cranial base length. PCA extracted eight components with 88.3% in the C-I group and seven components with 91.0% cumulative explanation in the C-II group. Conclusions Differences in the heritability of skeletodental characteristics between twin pairs with skeletal Class I and II malocclusions might provide valuable information for growth prediction and treatment planning.

The velopharyngeal mechanism is comprised of several muscular components that act in a coordinated manner to control airflow through the nose and mouth. Proper velopharyngeal function is essential for normal speech, swallowing, and breathing. The genetic basis of normal-range velopharyngeal morphology is poorly understood. The purpose of this study was to estimate the heritability of velopharyngeal dimensions. We measured five velopharyngeal variables (velar length, velar thickness, effective velar length, levator muscle length and pharyngeal depth) from MRIs of 155 monozygotic and 208 dizygotic twin pairs and then calculated heritability for these traits using a structural equation modeling approach. The heritability estimates were statistically significant (95% confidence intervals excluded zero) and ranged from 0.19 to 0.46. There was also evidence of significant genetic correlations between pairs of traits, pointing to the influence of common genetic effects. These results indicate that genetic factors influence variation in clinically relevant velopharyngeal structures.

Twin pregnancies are common and associated with pregnancy complications and adverse outcomes. Prenatal clinical management is intensive and has been hampered by inferior screening and less acceptable invasive testing. For aneuploidy screening, meta‐analyses show that non‐invasive prenatal testing (NIPT) through analysis of cell‐free DNA (cf‐DNA) is superior to serum and ultrasound‐based tests. The positive predictive value for NIPT is driven strongly by the discriminatory power of the assay and only secondarily by the prior risk. Uncertainties in a priori risks for aneuploidies in twin pregnancies are therefore of lesser importance with NIPT. Additional information on zygosity can be obtained using NIPT. Establishing zygosity can be helpful when chorionicity was not reliably established early in pregnancy or where the there is a concern for one versus two affected fetuses. In dizygotic twin pregnancies, individual fetal fractions can be measured to ensure that both values are satisfactory. Vanishing twins can be identified by NIPT. Although clinical utility of routinely detecting vanishing twins has not yet been demonstrated, there are individual cases where cf‐DNA analysis could be helpful in explaining unusual clinical or laboratory observations. We conclude that cf‐DNA analysis and ultrasound have synergistic roles in the management of multiple gestational pregnancies., Key Points What's already known about this topic? In singleton pregnancies, non‐invasive prenatal testing (NIPT) for fetal aneuploidy is more effective than conventional serum and ultrasound‐based screening tests.NIPT is more complex in dizygotic twin pregnancies due to the presence of two fetal genotypes.Overall fetal fraction is higher in twin pregnancies but the individual contribution for each fetus is lower. What does this study add? A review of cell‐free DNA testing in twin pregnancies.Individual fetal fractions in dizygotic twin pregnancies can be measured.Zygosity can be established using NIPT and this can be particularly useful when there are concerns about chorionicity or determining whether one versus two fetuses are affected.Vanishing twins can be detected through NIPT and this testing could be considered for some apparently singleton pregnancies with complications.

Background Propionic acidemia (PA) is a severe monogenic disorder characterized by a deficiency of the mitochondrial protein propionyl-CoA carboxylase (PCC) enzyme, which is caused by mutations in the PCCA or PCCB gene. Preconception carrier screening could provide couples with meaningful information for their reproductive options; however, it is not widely performed in China. Case presentation This report describes a case of dizygotic twin siblings conceived by in vitro fertilization (IVF) and diagnosed with propionic acidemia (PA). Their parents had no history of PA. Tandem mass spectrometry and urine gas chromatography/mass spectrometry (GC/MS) of the twin siblings revealed markedly elevated propionyl carnitine (C3), C3/C2, and 3-hydroxypropionate in the plasma and urine. Whole-exome sequencing was performed for the twin siblings. A homozygous missense mutation, c.2002G > A (p.Gly668Arg) in PCCA, was identified in the twin siblings. Sanger sequencing confirmed the homozygous mutation in the twin siblings and identified their parents as heterozygous carriers of the c.2002G > A mutation in PCCA. Both neonates in this case died. This is an emotionally and financially devastating outcome that could have been avoided with genetic carrier screening before conception. If couples are screened before IVF and found to be silent carriers, then reproductive options (such as preimplantation genetic diagnosis or prenatal diagnosis) can be offered to achieve a healthy newborn. Conclusion This case is a reminder to infertile couples seeking IVF that it is beneficial to clarify whether they are silent carriers before undergoing IVF.

Despite the evolution of transplantation techniques, urological complications are common and result in loss of graft. We report the case of a 57-year-old man who developed continuous urine leakage despite pyeloureteral neoanastomosis and stenting after kidney transplantation from his dizygotic twin. Suspecting ureteral leakage, we performed pyeloureteral neoanastomosis using his native right ureter and a ureteral stent 5 days after the kidney transplant. However, urine leakage continued for several days. Because the plasma factor XIII level decreased to 48%, we administered factor XIII products (Fibrogammin P; CSL Behring, King of Prussia, PA) after the surgery. Although its utility and safety in patients with renal failure and/or transplantation are unclear, urine leakage stopped after the infusion of fibrogammin without any side effects. This is the first case report of the use of factor XIII for refractory urine leakage after kidney transplantation. Although further studies are needed, administration of factor XIII products could be one option for refractory urine leakage after transplantation.

Isolated hypogonadotropic hypogonadism (IHH) is a rare genetic disorder that is clinically and genetically heterogeneous. It is characterized by absent or incomplete pubertal development owing to an isolated defect in the production, secretion, or action of gonadotropin-releasing hormone. The incidence of IHH is estimated at 1:30,000 in males and 1:125,000 in females. Although the vast majority of IHH cases are sporadic, some X-linked recessive, autosomal dominant, and autosomal recessive modes of inheritance have been described. IHH can be classified into Kallmann syndrome with anosmia and normosmic IHH. Here, we report dizygotic twin sisters with normosmic IHH who showed short stature and absence of puberty as a result of a variant of the FGFR1 gene. They had a normal sense of smell, and brain magnetic resonance imaging (MRI) showed well-defined olfactory bulbs. The older sister and the twins' mother had cleft palate, while the younger sister did not. The mother had menarche at the age of 16 years after hormonal replacement owing to delayed puberty. Molecular analysis of the FGFR1 gene identified a missense variant c.874C>G (p.His292Asp) in the twins and their mother. Herein, we described the clinical heterogeneity observed in the 2 affected twins who carry an identical variant in the FGFR1 gene. Further studies of the effects of modifier genes and epigenetic factors on the expression of FGFR1, as well as the various clinical manifestations of its mutations, are warranted.

BackgroundGenetically informed studies have provided mixed findings as to what extent parental substance misuse is associated with offspring substance misuse and antisocial behavior due to shared environmental and genetic factors.MethodsWe linked data from nationwide registries for a cohort of 2 476 198 offspring born in Sweden 1958–1995 and their parents. Substance misuse was defined as International Classification of Diseases diagnoses of alcohol/drug use disorders or alcohol/drug-related criminal convictions. Quantitative genetic offspring-of-siblings analyses in offspring of monozygotic and dizygotic twin, full-sibling, and half-sibling parents were conducted.ResultsBoth maternal and paternal substance misuse were robustly associated with offspring substance misuse [maternal adjusted hazard ratio (aHR) = 1.83 (95% confidence interval (CI) 1.80–1.87); paternal aHR = 1.96 (1.94–1.98)] and criminal convictions [maternal aHR = 1.56 (1.54–1.58); paternal aHR = 1.66 (1.64–1.67)]. Additive genetic effects explained 42% (95% CI 25–56%) and 46% (36–55%) of the variance in maternal and paternal substance misuse, respectively, and between 36 and 44% of the variance in substance misuse and criminality in offspring. The associations between parental substance misuse and offspring outcomes were mostly due to additive genetic effects, which explained 54–85% of the parent-offspring covariance. However, both nuclear and extended family environmental factors also contributed to the associations, especially with offspring substance misuse.ConclusionsOur findings from a large offspring-of-siblings study indicate that shared genetic influences mostly explain the associations between parental substance misuse and both offspring substance misuse and criminality, but we also found evidence for the contribution of environmental factors shared by members of nuclear and extended families.

Criminologists have long been interested in understanding the mechanisms that create male-female differences in criminal involvement. One possible explanation that has generated a significant amount of interest is whether testosterone—including exposure to prenatal testosterone—might be central to male-female disparities in crime. We use this possibility as a springboard to examine the potential association between prenatal testosterone and multiple criminogenic outcomes. To do so, we analyze a sample of female dizygotic twin pairs drawn from the National Longitudinal Study of Adolescent to Adult Health and employ a proxy measure of prenatal testosterone based off of the twin testosterone transfer (TTT) hypothesis. The analyses revealed that prenatal testosterone is not associated with nonviolent criminal involvement, violent criminal involvement, psychopathic personality traits, being arrested, and being incarcerated. Interestingly, there was a small association with low self-control, but the effect was in the opposite direction of expectations. We conclude by discussing the implications and limitations of our study as well as considerations for future research.

Metabolites are small molecules involved in cellular metabolism where they act as reaction substrates or products. The term ‘metabolomics’ refers to the comprehensive study of these molecules. The concentrations of metabolites in biological tissues are under genetic control, but this is limited by environmental factors such as diet. In adult mono- and dizygotic twin pairs, we estimated the contribution of genetic and shared environmental influences on metabolite levels by structural equation modeling and tested whether the familial resemblance for metabolite levels is mainly explained by genetic or by environmental factors that are shared by family members. Metabolites were measured across three platforms: two based on proton nuclear magnetic resonance techniques and one employing mass spectrometry. These three platforms comprised 237 single metabolic traits of several chemical classes. For the three platforms, metabolites were assessed in 1407, 1037 and 1116 twin pairs, respectively. We carried out power calculations to establish what percentage of shared environmental variance could be detected given these sample sizes. Our study did not find evidence for a systematic contribution of shared environment, defined as the influence of growing up together in the same household, on metabolites assessed in adulthood. Significant heritability was observed for nearly all 237 metabolites; significant contribution of the shared environment was limited to 6 metabolites. The top quartile of the heritability distribution was populated by 5 of the 11 investigated chemical classes. In this quartile, metabolites of the class lipoprotein were significantly overrepresented, whereas metabolites of classes glycerophospholipids and glycerolipids were significantly underrepresented.

The incidences of twin gestation and higher order multi-fetal pregnancies are on increasing trend. There are increased use of ovulation induction drugs and assisted reproductive technology in this era owing to higher incidences of infertility and better diagnostics and treatment modalities. And with increased use of these methods, comes increased incidence of complications. Incidences of complications are more in monozygotic pregnancies than in dizygotic twin. Acardiac twin is a rare, severe congenital malformation seen in monozygotic twin gestation, which is incompatible with life. Acardiac twin, also known as TRAP (Twin Reversed Arterial Perfusion Sequence); results from abnormal placental vasculature. Early diagnosis of acardiac twin by ultrasonography and colordoppler is essential for timely management and preventing complications like preterm delivery, cardiac failure and intrauterine fetal death of ‘ pump’co-twin. Here we are reporting a case of an antenatally diagnosed mono-chorionic twin pregnancy with acardiac twin, which was managed conservatively. Proper monitoring and timely decision for terminationresulted in preterm delivery of a live, normal twin along with an acardiac co-twin. Keywords: Pump twin, Acardiac twin, Monochorionic, Twin reversal arterial perfusion.

Higher levels of anger expression, as well as lower levels of anger control, have been reported for adults with anxiety disorders compared to individuals without anxiety disorders. Different to the research on adults, very few studies examined the relationship between anxiety and anger in childhood. In our study, we investigated 398 Italian twin pairs (74 MZ male, 70 MZ female, 134 same-sex dizygotic-53 male, 81 female-, and 120 unlike-sex dizygotic twin pairs), aged 8–17 (mean 13.06 ± 2.59): (i) the heritability of a childhood anger phenotype; (ii) the association between five anxiety domains and anger; (iii) the role of possible common etiological factors in explaining the observed comorbidity and overlap in the risk between anxiety phenotypes and anger. The study demonstrated that anger, assessed by CBCL items, is heritable in children at a similar rate to prior studies (40%). Our research found low to moderate rate of correlation between anger and anxiety (from 0.10 to 0.19). Finally, the present study found that the majority of etiological influences on anxiety and anger are independent of each other. Data showed that shared environmental influences have some small effects on the phenotypic covariation between the anxiety phenotypes and anger (12%); whereas unique environmental influences have an almost negligible effect (1%). Our analyses did not reveal the effect of genetic effects in explaining the covariation between these phenotypes.

The goal of this study was to explore the raters’ agreement and the effect of raters’ and targets’ gender on self- and parental intelligence assessments in the sample of Croatian twins. Twins were asked to assess their own and their parents’ overall intelligence, as well as specific abilities from the Gardner’s theory of multiple intelligences. Data was analysed to explore: i) twins’ agreement in parental assessments and behavioural genetic analysis of the overall intelligence estimates; ii) gender differences in self- assessments; and iii) raters’ and targets’ gender effects on parental assessments. The twins’ mean correlation in their assessments of overall parental intelligence was .60. The differences between monozygotic and dizygotic twin correlations were nonsignificant for all of the estimated abilities, and model fitting analysis indicates that hypothesis about genetic effect on parental assessment of intelligence should be rejected. The hypotheses about males’ higher self-assessments for overall intelligence and for the masculine types of abilities - logical-mathematical, body-kinesthetic and spatial abilities - were confirmed. For the feminine types of abilities - verbal/linguistic, inter- and intra- personal intelligences - there were no significant gender effects. Both target and rater effect were found for the parental estimates of intelligence. Fathers were estimated higher on overall intelligence, logical-mathematical, body-kinesthetic and spatial abilities, while mothers were estimated higher on interpersonal and intrapersonal intelligence. The effect of the raters’ gender was found for overall intelligence as well as for inter- and intra- personal intelligences, where males gave higher estimates of parental intelligences than females.

Purpose Early language and speech acquisition can be delayed in twin children, a twinning effect that diminishes between 4 and 6 years of age in a population-based sample. The purposes of this study were to examine how twinning effects influence the identification of children with language impairments at 4 and 6 years of age, comparing children with specific language impairment (SLI) and nonspecific language impairment (NLI); the likelihood that affectedness will be shared within monozygotic versus dizygotic twin pairs; and estimated levels of heritability for SLI and NLI. Twinning effects are predicted to result in elevated rates of language impairments in twins. Method The population-based twin sample included 1,354 children from 677 twin pairs, 214 monozygotic and 463 dizygotic, enrolled in a longitudinal study. Nine phenotypes from the same comprehensive direct behavioral assessment protocol were investigated at 4 and 6 years of age. Twinning effects were estimated for each phenotype at each age using structural equation models estimated via diagonally weighted least squares. Heritabilities were calculated for SLI and NLI. Results As predicted, the twinning effect increased the percentage of affected children in both groups across multiple language phenotypes, an effect that diminished with age yet was still not aligned to singleton age peers. Substantial heritability estimates replicated across language phenotypes and increased with age, even with the most lenient definition of affectedness, at −1 SD . Patterns of outcomes differed between SLI and NLI groups. Conclusions Nonverbal IQ is not on the same causal pathway as language impairments. Twinning effects on language acquisition affect classification of 4- and 6-year-old children as SLI and NLI, and heritability is most consistent in the SLI group. Clinical practice requires monitoring language acquisition of twins to avoid misdiagnosis when young or a missed diagnosis of language impairments at school entry.

Background and Aims:PCDH19 gene, which encodes protocadherin 19, is associated with epilepsy and intellectual disability, mainly in affected females. The clinical manifestations are heterogeneous and the main features include early onset seizure, generalized or focal seizures sensitive to fever, and brief seizures occurring in clusters. The disorders exhibit a unique and unusual X-linked pattern of expression. We aimed to investigate PCDH19 mutations/deletions in patients with epilepsy and describe the clinical/molecular features. Methods: PCDH19 gene was analyzed in 35 Turkish female patients from 34 families with early-onset epilepsy via direct sequencing and multiplex ligation-dependent probe amplification analysis. Additionally, array comparative genomic hybridization analysis was performed in patients with whole gene deletion. Results: We identified 2 different heterozygous mutations in 2 unrelated probands (5. 7%) which were located in exon 1. Additionally, whole gene deletions were detected in dizygotic twin girls (5. 7%), who had distinct clinical features and the deletion was inherited from the unaffected father. The second twin suffered more severe clinical manifestations including autistic features, behavioral problems, mild-moderate mental retardation and seizures, which were under control with multidrug regimen when compared with the first twin. Conclusion: PCDH19 is a major causative gene in patients with epilepsy and further data is required to gain a better understanding of phenotype-genotype correlation. In addition to gene sequencing, deletion/duplication analysis will improve the molecular diagnosis in patients with clinical findings.

Objective Results from twin studies examining the genetic overlap between type 2 diabetes and depression are currently inconclusive. This question has not been addressed in non-Western populations. We aimed to examine whether there are common genetic factors between type 2 diabetes and depression in a Sri Lankan population using genetic model-fitting analysis. Method The Colombo Twin and Singleton Study–Phase 2 consists of 2019 singletons, and 842 monozygotic and 578 dizygotic twin pairs. The primary outcomes were self-reported type 2 diabetes diagnosis and Beck Depression Inventory scores. Standard bivariate twin models were fitted to estimate the genetic and environmental (co)variance of type 2 diabetes and depression. Results In the best-fitting model, the phenotypic correlation between type 2 diabetes and depression was significant in female individuals only (r = 0.15 [0.08–0.21]). This association was primarily attributed to a significant genetic correlation between the traits (rA = 0.53 [0.19–0.98]). Conclusions In female individuals, but not male individuals, we found a significant genetic overlap between type 2 diabetes and depression in the context of a modest phenotypic correlation.