Female Monozygotic Twins Research Articles

A Case of Monozygotic Twins: The Value of Discordant Monozygotic Twins in Goldenhar Syndrome—OMIM%164210

Goldenhar syndrome is a rare developmental disorder characterised by hemifacial microsomia, epibulbar tumours, ear malformation, and vertebral anomalies. As monozygotic (MZ) twins are believed to be genetically identical, discordance for disease phenotype between MZ twins varies with craniofacial anomalies, cardiac, vertebral, and central nervous system defects sporadically. We report a case of monozygotic female twins discordant for Goldenhar syndrome with hemifacial microsomia and the dysplasia of auricular pinna.

Transsexuality Among Twins: Identity Concordance, Transition, Rearing, and Orientation

ABSTRACT The relative contributions of genetic and environmental factors to the development of gender identity have been debated. Twins were studied that are concordant or discordant for gender identity status in order to provide clarification of this issue. An extensive library search yielded reports of 27 male and 16 female sets concordant or discordant for transsexuality. An Internet bulletin board search and clinical contact requests for participants in a survey of twins in which one or both transitioned located 69 new twin pairs. In addition to asking about matters associated with gender, these new twins were asked about their transition, rearing, and sexual practices. Combining data from the present survey with those from past-published reports, 20% of all male and female monozygotic twin pairs were found concordant for transsexual identity. This was more frequently the case for males (33%) than for females (23%). The responses of our twins relative to their rearing, along with our findings regarding some of their experiences during childhood and adolescence show their identity was much more influenced by their genetics than their rearing.

Mirror-Image Identical Twins Presenting in Mirror-Image Hip Cysts: A Case Report and Review of the Literature

One-third of twins are monozygotic. Of monozygotic twins, 25% of them are mirror images. Mirror-imaging occurs when pathologic conditions are present on opposite sides of the body. This is the first case report of mirror-image identical twins with opposite hip pain that were found to have small cysts of the femoral head on opposite hips. Case presentation: 38 year-old mirror-image Asian female identical twins presented with hip pain on opposite sides. MRI demonstrated a 4 mm cyst of the anterior aspect of the left hip, the femoral head and neck junction, with a herniation pit on opposite sides. The right-handed twin had the cyst on the right hip, and the left-handed twin had the cyst on the left hip. Conclusion: Mirror-image pathology in mirror-image monozygotic twins suggests possible cytogenetic factors involved in the etiology of various medical problems. If an identical twin presents with a medical problem, it may be recommended to perform a medical diagnostic work-up on the other twin.

The Contribution of Endogenous and Exogenous Factors to Female Alopecia

Background:In this study, the authors investigated the potential contribution of environmental factors and testosterone levels on androgenic alopecia in women.Methods:Ninety-eight identical female twins were recruited from 2009 to 2011. Subjects were asked to complete a comprehensive questionnaire,

Microparticles and microscopic structures in three fractions of fresh cerebrospinal fluid in schizophrenia: Case report of twins

Schizophrenia is a diagnosis with a set of symptoms of aberrant psychological phenomena. Here, we discuss that there may be an imbalance of proteostasis of neurons in the brain leading to increase in membrane shedding and buildup of microparticles (MPs) appearing in the cerebrospinal fluid. The number of MPs can be determined and their phenotypes verified by size and membrane expression with flow cytometry. This is the first report of specified MPs in cerebrospinal fluid (CSF) in schizophrenia. Two 56-year-old Swedish-born female monozygotic twins of Caucasian ethnicity with onset of schizophrenia more than 30years ago were studied. Three fractions of fresh CSF were examined for microparticles by flow cytometry analysis, which measure the specific binding of antibodies to CD42a (platelet-MP; 33 GPIX), CD144 (endothelial-MP; Ve-cadherin), CD45 (leukocyte-MP; pan-leukocyte antigen) and of phosphatidylserine to lactadherin. The patients with schizophrenia displayed more phosphatidylserine-positive MPs in CSF compared with healthy control subjects. The scanning electron microscopic (SEM) structures in CSF studied over a 3-year period in twins with schizophrenia were of similar appearance at both time points. The increased number of MPs in fresh CSF may be a sign of enhanced membrane shedding in the central nervous system. Such MPs can be investigated for both human and non-human DNA, RNA and microRNA that may activate different immune signaling systems in patients with schizophrenia.

Monozygotic twins discordant for submicroscopic chromosomal anomalies in 2p25.3 region detected by array CGH

Although discordant phenotypes in monozygotic twins with developmental disorder are not an exception, underlying genetic discordance is rarely reported. Here, we report on the clinical and cytogenetic details of 4-year-old female monozygotic twins with discordant phenotypes. Twin 1 exhibited global developmental delay, overweight and hyperactivity. Twin 2 had an autistic spectrum disorder. Molecular karyotyping in twin 1 identified a 2p25.3 deletion, further confirmed by Fluorescence in situ hybridization (FISH) analysis on leukocytes. Interestingly, array comparative genomic hybridization was normal in twin 2 but FISH analysis using the same probe as twin 1 showed mosaicism with one-third of cells with a 2p25.3 deletion, one-third of cells with a 2p25.3 duplication, and one-third of normal cells. Genotyping with microsatellite markers confirmed the monozygosity of the twins. We propose that the chromosome imbalance may be due to a mitotic non-allelic recombination occurring during blastomeric divisions of a normal zygote. Such event will result in three distinct cell populations, whose proportion in each embryo formed after separation from the zygote may differ, leading to discordant chromosomal anomalies between twins. We also discuss that the MYTL1L and the SNTG2 genes within the reported region could probably relate to the phenotypic discordance of the monozygotic twins.

Birthweight discordant female twins and their offspring: is the intergenerational influence on birthweight due to genes or environment?

Does the intergenerational influence on birthweight and birth length remain within female dizygotic and monozygotic twin pairs? The intergenerational influence on birthweight and birth length remained within dizygotic but not within monozygotic twin pairs. Low birthweight is associated with increased morbidity and mortality in both the short and long term; therefore it is important to understand determinants of fetal growth. There is a known intergenerational association between parents' and offspring's size at birth. This is a register-based cohort study with a nested within-twin-pair comparison. The study is retrospective, but based on prospectively collected information. The study population included 8685 monozygotic and like-sexed dizygotic female twins born in Sweden from 1926 to 1985, who had given birth to their first infant between 1973 and 2009. This study is set in Sweden and used data from the Swedish Twin Register and the Swedish Medical Birth Register. We used generalized estimating equations to obtain regression coefficients with 95% confidence intervals (CI) for the outcomes: offspring birthweight and birth length. To control for genetic and shared environmental factors, we performed within-twin-pair analyses in 1479 dizygotic and 1526 monozygotic twin pairs. In the cohort of both dizygotic and monozygotic twins, there was an association between mother's and offspring's size at birth. Within-dizygotic twin pairs, a 500-g increase from the twin pair's mean birthweight was associated with increased offspring birthweight [70 g (95% CI: 35-106)] and birth length [0.22 cm (95% CI: 0.07-0.38)]. The corresponding increase in birth length of 1 cm was estimated to increase offspring's birthweight by 26 g (95% CI: 12-40) and birth length by 0.11 cm (95% CI: 0.04-0.17). Within-monozygotic twin pairs there were no such associations. This study is limited to twins who themselves or whose co-twin voluntarily responded to questionnaires. The intergenerational influence on size at birth is suggested to be due to direct or indirect genetic factors.

Oculo-facio-cardio-dental syndrome in three succeeding generations: genotypic data and phenotypic features

Oculo-facio-cardio-dental (OFCD) syndrome is a rare X-linked disorder mainly manifesting in females. Patients show ocular, facial, cardiac, and dental abnormalities. OFCD syndrome is caused by heterozygous mutations in the BCOR gene, located in Xp11.4, encoding the BCL6 co-repressor. We report a Croatian family with four female members (grandmother, mother and monozygotic female twins) diagnosed with OFCD syndrome who carry the novel BCOR mutation c.4438C>T (p.R1480*). They present high intrafamilial phenotypic variability with special regard to cardiac defect and cataract that showed more severe disease expression in successive generations. Clinical and radiographic examination of the mother of the twins revealed a talon cusp involving the permanent maxillary right central incisor. This is the first known report of a talon cusp in OFCD syndrome with a novel mutation in the BCOR gene.

Determinants of Breast Appearance and Aging in Identical Twins

Appearance, aging, and disorders of the breast are multifactorial. There are intrinsic, patient-specific characteristics, such as breast growth during puberty and propensity for breast cancer, which are primarily inherited. There are also environmental factors, which can be potentially controlled. Monozygotic twins provide an excellent research opportunity to examine the role of extrinsic factors in subjects with identical genetic predispositions. The authors investigate the role and significance of various environmental and acquired factors on breast aesthetics. Identical female twins were recruited during the Twins Days Festival in Twinsburg, Ohio, in 2009 and 2010. After consent was obtained, enrolled subjects completed a comprehensive survey on their medical and personal history. Standardized digital photographs were taken by medical photographers. Sixteen aesthetic breast features were subjectively rated by 6 plastic surgery residents blinded to the survey results. These ratings were then analyzed against survey data to determine the significance of different exogenous factors on breast appearance. A total of 161 pairs of identical female twins (n = 322) with a mean (SD) age of 47.6 (14.5) years were recruited. Twins who moisturized their skin daily had significantly fewer rhytids (P = .002). Twins who received hormone replacement therapy after menopause had more attractive breast shape, size, projection, areolar shape, and areolar size (P < .03). However, twins who had a higher body mass index, greater number of pregnancies, and larger cup sizes had significantly less attractive breasts (P < .05). Twins who smoked cigarettes and consumed alcohol also had significantly less attractive breasts (P < .05). Twins who breastfed had less attractive areolar size and shape but better skin quality than their counterparts who never breastfed (P < .03). Finally, there was a significantly higher incidence of breast pain in twins who primarily slept on their sides compared with twins who primarily slept on their backs (P < .008). This study implicates several environmental factors that significantly affect the aesthetic quality of breasts.

Congenital rubella syndrome: a continuing conundrum

A 32-year-old woman delivered monozygotic female twins vaginally at 34 weeks of gestation in November, 2011. This was her fourth pregnancy. She had received antenatal care elsewhere. During the fi rst trimester she had an episode of fever and rash. The rest of the antenatal period was uneventful. Both the twins had respiratory distress and were admitted to our neonatal intensive care unit. Both were given empirical antibiotic therapy and were mechanically ventilated. Echo cardiogram showed that twin one had a patent ductus arteriosus; weight was appropriate for gestational age. Twin two was small for gestational age and was covered with diff use purpura (fi gure), and had thrombocytopenia (platelet count 39×109/L) and retinitis. Radiography showed a radiolucent humerus bilaterally and intracranial calcifi cations. In view of the clinical features and maternal history of fever in the fi rst trimester, intrauterine infection was suspected. Both twins were positive for rubella specifi c IgM (chemiluminescent microparticle immunoassay; Abbott, Ireland) and negative for antibodies against toxoplasma and cytomegalovirus (CMV). The mother tested positive for both rubella and CMV specifi c IgG. Viral cultures could not be done because of lack of resources. Twin two succumbed to pulmonary haemorrhage on day 4. Twin one developed congestive cardiac failure on day 3 and was managed conservatively; she was extubated on day 5, and eventually discharged on medication for cardiac failure on day 12 having established direct breastfeeds. When she was last seen for follow-up in January, 2012, she had appropriate weight gain, tests for vision and hearing were normal, and her cardiac failure secondary to patent ductus arteriosus was under control. More than three decades have passed since the introduction of the live attenuated rubella vaccine. With widespread immunisation against rubella, the incidence of fetal exposure to rubella has decreased drastically, particularly in developed countries. However, rubella continues to aff ect women of childbearing age and young children in developing countries where vaccination against rubella is not covered under the national immunisation schedule. In our case, the diagnosis was made on the basis of the criteria for congenital rubella syndrome proposed by the US Centers for Disease Control and Prevention. Only a few studies have reported congenital rubella syndrome in twins. Only one twin in our case was severely aff ected, supporting the view that that there can be individual variation in disease expression. One study showed that in India, 82·2% of children between 1 and 5 years of age and 13·5% between 10 and 15 years of age were susceptible to rubella. Congenital rubella syndrome is a leading cause of non traumatic cataracts and hearing loss in children in developing countries. In India, more than 50% of children who underwent surgery for cataracts associated with congenital rubella syndrome had poor visual outcomes; most also had associated hearing loss. These facts underline the need for strengthening the rubella immunisation programme in India towards universal coverage in states that have not yet implemented it. Strong political will and a change in the constitution of the immunisation advisory groups could put an end to the problem of congenital rubella syndrome, and pave the way for its elimination as is being planned in the USA and the EU.

Effect of Body Composition Methodology on Heritability Estimation of Body Fatness.

Heritability estimates of human body fatness vary widely and the contribution of body composition methodology to this variability is unknown. The effect of body composition methodology on estimations of genetic and environmental contributions to body fatness variation was examined in 78 adult male and female monozygotic twin pairs reared apart or together. Body composition was assessed by six methods – body mass index (BMI), dual energy x-ray absorptiometry (DXA), underwater weighing (UWW), total body water (TBW), bioelectric impedance (BIA), and skinfold thickness. Body fatness was expressed as percent body fat, fat mass, and fat mass/height2 to assess the effect of body fatness expression on heritability estimates. Model-fitting multivariate analyses were used to assess the genetic and environmental components of variance. Mean BMI was 24.5 kg/m2 (range of 17.8–43.4 kg/m2). There was a significant effect of body composition methodology (p<0.001) on heritability estimates, with UWW giving the highest estimate (69%) and BIA giving the lowest estimate (47%) for fat mass/height2. Expression of body fatness as percent body fat resulted in significantly higher heritability estimates (on average 10.3% higher) compared to expression as fat mass/height2 (p=0.015). DXA and TBW methods expressing body fatness as fat mass/height2 gave the least biased heritability assessments, based on the small contribution of specific genetic factors to their genetic variance. A model combining DXA and TBW methods resulted in a relatively low FM/ht2 heritability estimate of 60%, and significant contributions of common and unique environmental factors (22% and 18%, respectively). The body fatness heritability estimate of 60% indicates a smaller contribution of genetic variance to total variance than many previous studies using less powerful research designs have indicated. The results also highlight the importance of environmental factors and possibly genotype by environmental interactions in the etiology of weight gain and the obesity epidemic.

Discordant phenotypes in monozygotic twins with identical de novo WT1 mutation

Mutations in the WT1 gene, leading to Denys-Drash syndrome and Frasier syndrome, can also cause isolated steroid-resistant nephrotic syndrome (ISRNS). Previous studies have reported six pairs of monozygotic twins with WT1 mutations, including one presenting with discordant phenotypes with identical WT1 mutations being of paternal origin and five pairs of monozygotic twins presenting the same phenotype with identical WT1 mutations. In this study, we report on female monozygotic twins showing discordant phenotypes with an identical de novo WT1 mutation, R394W, and presenting incomplete Denys-Drash syndrome and ISRNS.

Feeling of Cold Hands and Feet is a Highly Heritable Phenotype

The prevalence of the feeling of cold hands and feet (FCHF) is high in the general population but the etiology of FCHF is largely unknown. The aim of the present study was to explore whether the FCHF is heritable. Eight hundred and ninety-four pairs of twins completed a question about FCHF. Tetrachoric correlations for FCHF were .58, .29, .67, .52, and .04 for monozygotic male, dizygotic male, monozygotic female, and dizygotic female twins, respectively. Model-fitting analyses suggested that in the best fitting model, additive genetic and nonshared environmental variance including measurement error were 64% (95% CI: 55%-72%) and 36% (28%-45%), respectively. Sex differences in genetic and environmental influences were not significant.

Abstract P194: Gene-Environment Interactions and Blood Lipid levels: a Twin Study

Genetic variation may affect blood lipid levels by directly determining levels (‘level genes’) and/or by influencing the response to environmental factors (‘variability genes’), i.e. gene-environment interaction. Previous dietary studies assessing variability gene effects have produced inconsistent results, perhaps due to a lack of statistical power, different dietary protocols, and/or differences in the age, sex, habitual diet, baseline lipid values and other genes of the participants. Monozygotic (MZ) twins can enhance our ability to identify variability genes because they are genetically identical and also share the same age, sex and aspects of their early environment. Therefore, all intrapair differences in blood lipid levels are due to environmental factors such as diet and lifestyle, and variation between genotypes in intrapair differences will indicate the existence of variability genes. We investigated the hypothesis that polymorphisms within the genes for apoB, apoE and lipoprotein lipase influence the blood lipid response to environmental factors. The subjects studied were 64 MZ male and female twin pairs aged 18-75 years who had been recruited for a study of coronary heart disease risk factors in twins. Blood samples already taken for analysis of fasting lipid levels were used for DNA extraction. Genotypes were determined for the polymorphisms apoB signal peptide insertion/deletion (I/D), apoB Xba I, apoE, and lipoprotein lipase Pvu II, Hind III and S447X. Mean intrapair differences in lipid levels adjusted for mean twin pair lipid level were calculated for each genotype group. In MZ twins, carriers of the apoB signal peptide D allele had smaller intrapair differences in total cholesterol (p=0.044) but larger intrapair differences in apoAI (p=0.035) than I/I twins, and apoE ε4 carriers had smaller intrapair differences in HDL-cholesterol than E3/3 and E3/2 twins (p=0.024). MZ twins with the Pvu II P-P- genotype had significantly greater intrapair differences in apoB than P-P+ or P+P+ twins. The Xba I, Hind III and S447X polymorphisms did not influence intrapair differences in lipid levels. In conclusion, the apoB signal peptide I/D, apoE and lipoprotein lipase Pvu II polymorphisms may act as variability genes and influence the susceptibility of blood lipid levels to dietary and pharmacological interventions for dyslipidaemia. The approach of using MZ twins to identify variability genes can be applied to other phenotypes, prior to determining the environmental factors that interact with the genes to influence the phenotype.

Gender Identity Disorder in Twins: A Review of the Case Report Literature

The etiology of gender identity disorder (GID) remains largely unknown. In recent literature, increased attention has been attributed to possible biological factors in addition to psychological variables. To review the current literature on case studies of twins concordant or discordant for GID. A systematic, comprehensive literature review. Of 23 monozygotic female and male twins, nine (39.1%) were concordant for GID; in contrast, none of the 21 same-sex dizygotic female and male twins were concordant for GID, a statistically significant difference (P=0.005). Of the seven opposite-sex twins, all were discordant for GID. These findings suggest a role for genetic factors in the development of GID.

Cyberspace Chat

1. Sharon A. Keene, MD (drkeene{at}hairrestore.com) 1. Tucson, Arizona, USA ![][1] In the last Cyberchat column, a discussion began with Mike Beehner’s presentation of monozygotic female twins who, despite their identical genotype, had remarkably different degrees of hair

Functional neuroimaging study in identical twin pairs discordant for regular cigarette smoking

Despite the tremendous public health and financial burden of cigarette smoking, relatively little is understood about brain mechanisms that subserve smoking behavior. This study investigated the effect of lifetime regular smoking on brain processing in a reward guessing task using functional magnetic resonance imaging and a co-twin control study design in monozygotic (MZ) twin pairs that maximally controls for genetic and family background factors. Young adult (24-34 years) MZ female twin pairs (n = 15 pairs), discordant for regular smoking defined using Centers for Disease Control criteria as having smoked ≥100 cigarettes in their lifetime, were recruited from an ongoing genetic epidemiological longitudinal study of substance use and psychopathology. We applied hypothesis-driven region of interest (ROI) and whole-brain analyses to investigate the effect of regular smoking on reward processing. Reduced response to reward and punishment in regular compared with never-regular smokers was seen in hypothesis-driven ROI analysis of bilateral ventral striatum. Whole-brain analysis identified bilateral reward-processing regions that showed activation differences in response to winning or losing money but no effect of regular smoking; and frontal/parietal regions, predominantly in the right hemisphere, that showed robust effect of regular smoking but no effect of winning or losing money. Altogether, using a study design that maximally controls for group differences, we found that regular smoking had modest effects on striatal reward processing regions but robust effects on cognitive control/attentional systems.

The Second to Fourth Digit Ratio (2D:4D) in a Japanese Twin Sample: Heritability, Prenatal Hormone Transfer, and Association with Sexual Orientation

The second to fourth digit ratio has been argued to reflect prenatal hormonal influences and is reportedly associated with various psychological and behavioral traits, such as sexual orientation, cognitive abilities, and personality. We examined genetic and environmental influences on the second to fourth digit ratio (2D:4D) using a Japanese twin sample (N=300). The genetic analysis showed substantial additive genetic influences for both right and left hand 2D:4D. The rest of the variance was explained mainly by environmental influences not shared within twin pairs. These findings were, in general, in accordance with preceding studies with primarily Caucasian twin samples. The bivariate genetic analysis revealed that the additive genetic influences were largely shared between the right and left hand, while the non-shared environmental influences were largely unique to each hand. Results from a comparison of opposite-sex and same-sex twins were not significant, although they were in the predicted direction according to the prenatal hormone transfer hypothesis. Female monozygotic twin pairs discordant in sexual orientation showed significant within-pair differences in left hand 2D:4D, where non-heterosexual twins had lower (more masculinized) 2D:4D. In addition, we found that non-heterosexual male MZ twins had larger (more feminized) 2D:4D than their heterosexual co-twins. These results suggest the existence of non-shared environmental influences that affect both 2D:4D and sexual orientation.

Fear Processing and Social Networking in the Absence of a Functional Amygdala

The human amygdala plays a crucial role in processing social signals, such as face expressions, particularly fearful ones, and facilitates responses to them in face-sensitive cortical regions. This contributes to social competence and individual amygdala size correlates with that of social networks. While rare patients with focal bilateral amygdala lesion typically show impaired recognition of fearful faces, this deficit is variable, and an intriguing possibility is that other brain regions can compensate to support fear and social signal processing. To investigate the brain's functional compensation of selective bilateral amygdala damage, we performed a series of behavioral, psychophysiological, and functional magnetic resonance imaging experiments in two adult female monozygotic twins (patient 1 and patient 2) with equivalent, extensive bilateral amygdala pathology as a sequela of lipoid proteinosis due to Urbach-Wiethe disease. Patient 1, but not patient 2, showed preserved recognition of fearful faces, intact modulation of acoustic startle responses by fear-eliciting scenes, and a normal-sized social network. Functional magnetic resonance imaging revealed that patient 1 showed potentiated responses to fearful faces in her left premotor cortex face area and bilaterally in the inferior parietal lobule. The premotor cortex face area and inferior parietal lobule are both implicated in the cortical mirror-neuron system, which mediates learning of observed actions and may thereby promote both imitation and empathy. Taken together, our findings suggest that despite the pre-eminent role of the amygdala in processing social information, the cortical mirror-neuron system may sometimes adaptively compensate for its pathology.

Chondromyxoid fibroma of C1: first case report

BACKGROUND: Chondromyxoid fibroma (CMF) is a rare, benign primary bone tumor. The cervical spine is an uncommon site for this tumor, with only 10 reported cases to date and none involving the first cervical vertebra (C1). CASE REPORT: Female patient, 25-year-old monozygotic female twin, presented with cervical pain. Radiographic imaging demonstrated a contrast-enhanced, right-sided lytic lesion of the insufflated type in C1, with a punched-out appearance and extending to the anterior arch. A postero-lateral and a posterior approach were performed in two steps to resect the tumor followed by occipitocervical fixation. Pathology confirmed the diagnosis of CMF. At one year, the patient remains disease free with excellent spinal stability. CONCLUSION: Spinal surgeons may need to treat rare spinal tumors. Despite the proximity to neural and vascular structures, the goal of surgery is always a radical resection due to high recurrence rates.