The Value of Twins for Health and Medical Research: A Third of a Century of Progress.

In 1984, Hrubec and Robinette published what was arguably the first review of the role of twins in medical research. The authors acknowledged a growing distinction between two categories of twin studies: those aimed at assessing genetic contributions to disease and those aimed at assessing environmental contributions while controlling for genetic variation. They concluded with a brief section on recently founded twin registries that had begun to provide unprecedented access to twins for medical research. Here we offer an overview of the twin research that, in our estimation, best represents the field has progress since 1984. We start by summarizing what we know about twinning. We then focus on the value of twin study designs to differentiate between genetic and environmental influences on health and on emerging applications of twins in multiple areas of medical research. We finish by describing how twin registries and networks are accelerating twin research worldwide.

Management of congenital midline nasofrontal dermoid cysts in two identical twins: Case report.

Midline dermoid cysts are uncommon lesions that can lead to severe complications when an intracranial extension exists. We report the cases of two twin sisters referred to surgery for removal of the masses and the intracranial extension. They represent an additional example of familial nasal dermoid cysts, providing further support for a genetic basis for the disorder.

Discordant immune complete heart block and growth restriction in dichorionic twin pregnancy with permanent pacemaker implantation of an 1140 g neonate.

Fetal atrioventricular block is a rare pathology, mostly due to placental transmission of maternal SSA/Ro and SSB/La antibodies, and can lead to severe fetal or neonatal outcomes. We report a case of dichorionic, diamniotic twin pregnancy, with maternal SSA/Ro antibodies. Isolated complete atrioventricular block was diagnosed at 23 weeks in one fetus (Twin A), while the second fetus (Twin B) remained in normal sinus rhythm. Severe asymmetric intrauterine growth restriction occurred in Twin A. Delivery was by caesarean section at 32 + 2 weeks. Neonatal permanent pacemaker was inserted on the first day after birth in 1140 g neonate. Discordant heart block in twin pregnancy has already been reported in a few dichorionic pregnancies, but the pathway of discordant disease expression remains unclear. Extraction decision is a dilemma between cardiac failure prevention and prematurity associated twin morbidity. This case shows a successful pacing in a very low birth weight neonate.

A classic twin study of lower urinary tract obstruction: Report of 3 cases and literature review.

OBJECTIVE: The aim of the present study was to investigate genetic effects in the formation of congenital lower urinary tract obstruction (LUTO) comprising posterior urethral valves (PUV), urethral atresia, and urethras with variable degrees of stenosis. METHODS: A classic twin study was performed by assessing LUTO twin pairs from the literature. Furthermore, data regarding 3 previously unreported twin pairs with PUV from University of Bonn, Essen and Wroclaws own in-house databases were added. Both pair- and probandwise concordance rates were calculated and compared for monozygotic (MZ) and dizygotic (DZ) twin pairs. RESULTS: The pairwise concordance rates for all LUTO were 53% (95% confidence interval [CI] 32%-73%) and 17% (95% CI 3%-56%) for MZ and DZ twin pairs, respectively (P = .180). The probandwise concordance rates were 69% (95% CI 51%-83%) and 29% (CI 95% 8%-64%) for MZ and DZ twin pairs respectively (P = .084). The MZ/DZ ratios of the pair- and probandwise concordance rates were 3.1 and 2.4, respectively. CONCLUSION: The present study did not show significant differences in comparisons of concordance rates of MZ and DZ twin pairs, probably due to the small number of twin pairs reported. However, the more than 2-fold higher pair- and probandwise concordance rates for MZ versus DZ twin pairs are very suggestive of a contribution of genetic factors to the development of LUTO.

Congenital tuberculosis after in vitro fertilization: suggestion for tuberculosis tests in infertile women in developing countries.

Congenital tuberculosis (CTB) after in vitro fertilization (IVF) is a major new problem in developing countries. Only 16 cases of CTB after IVF have been reported, and no tuberculosis (TB) tests were performed before IVF in these cases. However, on the basis of data in the literature and from the World Health Organization, the incidence of CTB has been substantially underestimated. We describe two cases of CTB after IVF in detail in our center and provide new insight into the important issue of controlling TB vertical transmission in developing countries. Performing an early diagnosis of CTB, mostly based on evidence of maternal infection and a high index of clinical suspicion, is a challenge. However, most mothers have no symptoms of TB infection during prepartum, and infertility may be the only symptom. Infertility caused by genital TB is common in countries with a high TB burden, and IVF is considered to be an effective treatment to improve their fertility. Therefore, this may lead to more CTB cases without thorough TB tests before IVF. We suggest that thorough TB tests should be conducted in infertile women before IVF to prevent CTB.

[Periorbital, blue tumour in newborn twins]. / Periorbitale, blauwe zwelling bij pasgeboren tweeling.

Newborn twins both had a blue, smooth tumour in the inner angle of the orbit; one of them had two such tumours. They were diagnosed with congenital dacryocystoceles. If decompression into the nose is not effective, patients should undergo probing early in life to reduce the incidence of dacryocystitis and orbital cellulitis.

Poor oral intake in a late preterm twin - usual symptom with an unusual diagnosis.

BACKGROUND: At three weeks of age, a previous 34 weeks' gestation male infant (twin A) was transferred to our regional perinatal center (RPC) with complaints of poor oral feeding and intermittent tachypnea. Twin B was discharged at 37 weeks with an uneventful course. CASE: Twin A briefly required respiratory support but continued to have difficulty transitioning from gavage to oral feeding. Initially, his inability to feed orally was thought to be secondary to nasal congestion and prematurity, but with worsening respiratory distress he was transferred for further evaluation and management. DIAGNOSIS & CONCLUSION: On admission to RPC, the examination prompted a cardiac assessment which revealed a large aortic-pulmonary window type II. After surgery, the infant quickly improved and went home on-demand oral feeds. Cardiac lesions are more common in monochorionic twins but should be suspected in dichorionic twins especially if one twin has a normal course.

Laparoscopic repair of congenital duodenal obstruction is feasible even in small-volume centres.

INTRODUCTION It has been suggested that laparoscopic repair of congenital duodenal obstruction (CDO) should be restricted to a limited number of designated centres of expertise. After gaining extensive experience with intracorporeal suturing in other procedures, we evaluated the feasibility of this approach at the Royal Hospital for Sick Children (RHFSC; Edinburgh, UK). METHODS We conducted a retrospective review of all cases of CDO presenting to the RHFSC from 2012 to 2014. Cases were identified from our electronic database using standardised codes. Data comprised: gestation; birth weight; associated anomalies; patient age and weight at surgery; operative time; complications; postoperative course. RESULTS Five consecutive non-selected cases of isolated CDO were repaired laparoscopically, and all were carried out by the senior surgeon. The male:female ratio was 4:1. Corrected gestational age at surgery was 35-38 weeks, and the weight at surgery was 1.7-3.1 kg. None of our patients had significant associated anomalies. CONCLUSIONS The present study demonstrates the feasibility of laparoscopic repair of CDO in small-volume centres, and is the first report of laparoscopically managed congenital duodenal atresia in twins.

Acardiac twinning: High resolution three-dimensional reconstruction of a low resistance case.

BACKGROUND: Acardiac twinning is a rare anomaly of monochorionic twin pregnancies. Acardiac fetuses lack a functional heart but are passively perfused by arterial blood from their pump co-twin. Although four acardiac morphological types have been classified, the various paths of anatomical and circulatory acardiac twin development, and the potential influence of acardiac size and perfusion flow as possible predictors of pump twin morbidity and mortality are poorly understood. This report presents the first high resolution three-dimensional reconstruction of the vasculature of an acardiac twin by cryomicrotome imaging. CASE: A small, approximately 7.5-cm-diameter ball-shaped acardius amorphous of 30 5/7 weeks had caused pump twin cardiac decompensation that necessitated an emergency cesarian section. The pump twin survived well. The acardiac body had a partially intact vascular system with large diameter arteries and veins and multiple zones that appeared devoid of perfusion. The three-dimensional reconstruction showed neither recognizable organ structures nor identifiable blood vessels except for the umbilical artery and vein. CONCLUSION: Our case showed a small acardiac mass with large diameter vessels and consequential low outflow resistance that caused pump twin complications. This indicates that the development of a method that allows pump twin prognosis is likely more successful if based on the use of acardiac versus pump twin perfusion flows than on body volume ratios.

Premature newborns with fatal intrauterine herpes simplex virus-1 infection: first report of twins and review of the literature.

BACKGROUND: Neonates with blistering skin diseases are dermatologic emergencies. The pathologies involved can pose diagnostic difficulties and there exists a variety of potential life-threatening differential diagnoses. OBJECTIVE: description of the first case of intrauterine acquired herpes simplex virus (HSV) 1 infection in twins. METHODS: We present the case of two premature bicordial biamniotic twins (27th week of gestation) whose intrauterine growth retardation, fetal anaemia and cardiotocography abnormalities led to a caesarean emergency delivery. RESULTS: Accurate medical history revealed a maternal febrile gingivostomatitis at the 23rd week of gestation, which was neglected by the treating gynaecologist. Respiratory distress was present at delivery and intubation was necessary in both children. The whole skin showed extensive erosions and ulcerations and the mucosa of the eyes and genitals was also involved. Intrauterine Herpes simplex virus (HSV) 1 infection was confirmed by immunohistochemistry of skin Tzanck smear (HSV 1 positive, HSV 2 negative), real-time polymerase chain reaction of both serum and skin (HSV 1 positive; HSV 2 negative) and maternal serology positive for HSV 1 IgM and IgG. Siblings were immediately treated with high-dose endovenous acyclovir. Anaemia thrombocytopenia and hepatorenal values markedly deteriorated and both developed consequential hepatorenal failure. The third day live supportive measures were terminated after parental informed consent and both siblings deceased shortly after on their mother's breast. DISCUSSION: Intrauterine HSV infection is rare and accounts only for 5% of neonatal HSV infections. Literature reports only 64 cases and 90% of those are related to HSV-2. Transplacental viral transmission is highest during the first 20 weeks of gestation and has been observed in pregnant women with disseminated HSV infection. Mortality and morbidity of intrauterine herpetic infection are extremely high. CONCLUSION: Despite transplacental HSV transmission remains a rare event, the potential devastating outcome justifies immediate adequate antiviral treatment in a pregnant woman affected by primary HSV infection.

Limb hypoplasia resulting from intrauterine infection with herpes simplex virus: a case report.

Intrauterine infection with herpes simplex virus, although very rare, has devastating effects on multiple organ systems in the fetus and can lead to in utero fetal demise. Neonates born following intrauterine herpes simplex virus infection commonly manifest with cutaneous lesions, ocular damage and/or brain abnormalities. We describe the case of a dichorionic, diamniotic twin gestation complicated by intrauterine herpes simplex virus infection. This infection led to the fetal demise of twin A and a very uncommon presentation of limb hypoplasia in twin B.

Factors contributing to facial asymmetry in identical twins.

BACKGROUND: This study examines the potential contributions of environmental factors to variations in facial symmetry between identical twins. METHODS: Identical male and female twins were recruited from the Twins Days Festival in 2009 and 2010. Subjects independently completed a comprehensive questionnaire on their medical and personal history, and then posed for digital facial photography from several different angles. Eight facial features from these photographs were measured using Adobe Photoshop, and these facial features were then analyzed against survey responses between twins through multivariate regressions. RESULTS: A total of 147 pairs of identical twins were included. Twins who slept primarily prone had greater nasal midline deviation (p = 0.047) and oral commissure asymmetry (p = 0.027). Tooth extractions were significantly associated with canting of the plane of occlusion (p = 0.043), and use of dentures was associated with nasal midline deviation (p = 0.032) and oral commissure asymmetry (p = 0.007). Smoking was associated with canting of the plane of occlusion (p = 0.049) and upper eyelid ptosis (p = 0.023). Lastly, headaches were also associated with nasal midline deviation (p = 0.024). CONCLUSION: Exogenous factors such as prone sleep position, tooth extractions, dentures, and smoking are significant risk factors for facial asymmetry. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

The innate immune response status correlates with a divergent clinical course in congenital Chagas disease of twins born in a non-endemic country.

The innate immune response from diamniotic and dichorionic twin brothers congenitally infected with Trypanosoma. cruzi (strain DTU-V) who displayed different clinical symptomatology was studied. While Brother I manifested severe cardiac and digestive disorders, the Brother II showed slight splenomegaly. The secretion level of IL-1ß, TNF-α, IL-12, IL-10, IFN-α and IL-6 cytokines produced after stimulation of peripheral blood cells with TLR-2, TLR-4 and TLR-9 ligands was determined pre- and post-benznidazole treatment. Cells from 10 uninfected infants born to mothers seropositive for Chagas disease were included as control. The obtained data show that the cells of Brother I secreted lower levels of the pro-inflammatory cytokines IL-1ß and TNF-α (upon TLR-2 and TLR-4 stimulation) relative to those secreted by cells from Brother II and uninfected controls. The cells from Brother II secreted high levels of the IL-1ß cytokine following TLR-2 stimulation relative to uninfected controls. The cells from both brothers secreted a higher level of IL-6, following TLR-4 stimulation, than that secreted by uninfected infant cells. After treatments, the cytokine secretion levels were similar in both children and comparable to those of uninfected donors. Treatment success in Brother I and treatment interruption in Brother II was detected by the use of serological biomarkers (KMP11, HSP70, PFR2, Tgp63) as well as follow-up done by PCR. Therefore, the Brother II required a second treatment. The data presented suggest that benznidazol treatment allows the innate immune system to reach a fully functional status similar to that of uninfected subjects.

Connatal cyst in a preterm twin infant with maternal comorbidities.

BACKGROUND: Connatal cysts are rare but recognized periventricular cysts that represent anatomic variants and are associated with good neurological outcomes. These cysts can be differentiated from cysts that portend graver prognoses by their location in relation to the ventricles, size, laterality, and temporal resolution. PATIENT PRESENTATION: We describe a preterm twin infant born to a mother with diabetes and cardiovascular disease who was found to have connatal cysts on head ultrasound at 3 days of age. These cysts were present again on head ultrasound at 12 days of age and on brain magnetic resonance imaging at 27 days of age. The infant had a normal neurological examination in the neonatal period and on follow-up at 3 and 6 months of age. Repeated head ultrasound at 3 months of age demonstrated near resolution of the cysts. CONCLUSION: Connatal cysts are normal anatomic variants which clinicians should be able to distinguish from similar appearing cysts with less favorable outcomes. Although the etiology of connatal cysts remains unknown, this case raises the possibility of maternal comorbidities or perinatal hypoperfusion playing a role in their formation.

Complicações fetais na gemelaridade monocoriônica: quadro clínico, fisiopatologia, diagnóstico e conduta / Fetal complications in monochorionic twin pregnancy: clinical features, pathophysiology, diagnosis and management

A incidência de gemelaridade monocoriônica é de um para cada duzentos e cinquenta gestações. A placenta monocoriônica está relacionada a maior risco de complicações gestacionais, como transfusão feto-fetal, restrição seletiva do crescimento fetal, óbito fetal e gêmeo acárdico. Portanto, a avaliação criteriosa da corionicidade, o monitoramento da gestação e a detecção precoce de complicações são fatores importantes para melhorar o desfecho neonatal. Assim, o objetivo deste estudo é descrever as principais complicações fetais da gestação monocoriônica e qual deve ser a conduta obstétrica diante das diversas situações adversas. Foi realizada uma revisão de literatura dos últimos 28 anos, nas bases de dados MEDLINE/Pubmed, Scielo, LILACS e BIREME, sendo encontrados 401 artigos. Dentre estes, 28 estudos foram selecionados para esta revisão.(AU)

The incidence of monochorionic twin pregnancy is one in every two hundred and fifty pregnancies. The monochorionic placenta is associated with higher risk of pregnancy complications, such as fetal-fetal transfusion, selective fetal growth restriction, fetal death and acardiac twin. Therefore, a careful assessment of chorionicity, monitoring of pregnancy and early detection of complications are important factors to improve neonatal outcomes. Thus, the aim of this study is to describe the major fetal complications of monochorionic pregnancy and the better and what should be the obstetric approach considering the various adverse situations. A literature review of the past 28 years was performed in MEDLINE/PubMed, SciELO, LILACS and BIREME, being found 401 articles. Of these, 28 studies were selected for this review.(AU)