First documented cases of heteropaternal superfecundation in dizygotic twins from the Dominican Republic: A case report

Myelomeningocele (MMC) is a common subtype of congenital neural tube defects (NTD). Although congenital malformations including NTD are more common in twins, concordance, especially in dizygotic twins, is extremely rare and is found mostly in same-sex twins. The role of genetic and environmental factors in the etiology of MMC is unclear. Dizygotic twins of opposite sex were born at term to a 35-year-old woman conceived with in vitro fertilization (IVF) using intracytoplasmic sperm injection (ICSI). Prenatal ultrasonography (US) revealed concordant lumbosacral MMC at 18weeks of gestation as well as ventriculomegaly and Arnold-Chiari malformation type II at 28weeks. Both twins underwent surgical repair of the MMC within 48h after birth and required a ventriculoperitoneal shunt in the second week of life. The case presented raises questions concerning the etiology of MMC, since in twins, it is compelling to attribute the etiology to genetic factors. In the literature, 22 pairs of twins with concordant MMC have been reported, and of the 10 dizygotic twins described, four were of opposite sex. However, in monozygotic twins, most of the cases are non-concordant; therefore, the role of genetics remains unclear. In addition, environmental factors such as nutrition, metabolic folic acid deficiency, and assisted conception with IVF and ICSI might play a role as well. The appearance of concordant MMC in opposite-sex dizygotic twins, conceived by IVF using ICSI, intrigues questions concerning the etiology of MMC. In such cases, genetic counseling and evaluation should be considered.

Superfecundation, the fertilization of two oocytes by different spermatozoa within the same ovulatory cycle, can result in monopaternal or heteropaternal dizygotic twins. While monopaternal superfecundation is more common, heteropaternal superfecundation is rare and typically seen in disputed paternity cases. This study presents a case of heteropaternal superfecundation confirmed through forensic DNA analysis and reviews its occurrence in existing literature. A forensic investigation was conducted in a court-ordered paternity case involving dizygotic twins, their mother, and an alleged father. Buccal swab samples were collected and analyzed using multiplex amplification of 19 STR markers and the amelogenin locus. A second DNA test confirmed the results. Additionally, a dataset of 2,679 paternity tests over 10 years was examined to estimate paternity exclusion rates in twin cases. Genetic analysis confirmed the alleged father's paternity of twin 1 but not twin 2, with 14 out of 19 STR loci showing absent alleles in twin 2. The 10-year dataset showed 553 paternity exclusions (20.64% of cases), with 31 involving twins, of which one case (3.23%) was identified as heteropaternal superfecundation. No significant difference was found between paternity exclusion rates in twin and non-twin cases. This case underscores the value of forensic genetic testing in detecting heteropaternal superfecundation, a rare occurrence with legal and social implications. Advances in DNA analysis may lead to more frequent identification of such cases.

Heteropaternal superfecundation (HP) occurs when two or more ova are fertilized by sperm from separate males. The resulting siblings are genetically equivalent to half-siblings and share, on average, 25% of their inherited genetic material. In the absence of genetic testing HP siblings could be treated as dizygotic (DZ) twins in behavioral genetic analyses and bias heritability estimates in phenotypic decomposition models. However, the extent to which such misclassification could affect calculated estimates of heritability is currently unknown. Employing simulation analyses, the current study assessed the potential biasing impact across a variety of conditions varying by proportions of DZ twins, sample sizes, and low, moderate, and high levels of genetic and environmental contribution to phenotypic variance. Overall, the results indicated that misclassified HP siblings had minimal impact on estimates of heritability. Nonetheless, greater attention should be paid to the identification of HP siblings within existing and future twin datasets.

The base paper calls for urgent implementation of activities to achieve the targets for TB control set by the 1991 World Health Assembly, the 2015 Millennium Development Goals and the Stop TB Partnership. Laserson & Wells conclude that the greatest challenge is the devastating impact of the HIV epidemic. They suggest that countries will only achieve success with an accelerated political commitment to TB/HIV collaborative activities through national revised plans built upon the Stop TB Strategy and the Global Plan to Stop TB 2006–2015. The Dominican Republic faces several challenges in addressing these targets. While the incidence of all forms of TB in the Dominican Republic has been estimated to be among the highest in the Americas (91 cases per 100 000 people in 2005),1 much progress has been achieved since the implementation of DOTS in 1999. By 2005, DOTS services had been made available to 80% of the population and detection of infectious cases was 83% for the whole country and 76% in DOTS areas. The 2003 cohort analysis suggested 80% treatment success.1 Funding for TB control has been secured for the next 3 to 5 years and technical support has been provided. A steady supply of high-quality anti-TB drugs has been assured via the Global Drug Facility, fixed-dose combinations have been introduced and a MDR-TB unit has recently been created. This impressive list of achievements was realized in a short period of time. However, to ensure sustainability and guarantee that targets are reached, 5- to 10-year national planning in line with the Global Plan to Stop TB 2006–2015 and implementation of the new Stop TB Strategy are vital. The Dominican national TB programme and its partners face several of the barriers acknowledged in the base paper. Notably, the latest data suggest that progress to address TB/HIV, MDR-TB and XDR-TB has been slow. Data on TB/HIV coinfection, which are limited to certain areas of the country, suggest that between 6% and 11% of TB patients are infected with HIV.2,3 A recent survey suggests that young adults, provinces with a high rate of tourism and sugar-mill camps should be targeted for interventions.3,4 While the country has introduced some TB/HIV collaborative activities (e.g. isoniazid prophylaxis for HIV-infected people and provision of antiretroviral drugs), there are no data on the number of HIV-infected TB patients receiving antiretroviral drugs. There is no surveillance of HIV among TB patients, no information is available on coinfected patients receiving cotrimoxazole, and a proper referral/counter referral mechanism for patients has not been established. Collaboration between TB and HIV/AIDS programmes needs to advance immediately and concretely in line with the new Stop TB Strategy.5 The recent development of national TB/HIV guidelines and inclusion of TB/HIV activities on national plans are steps in this direction. MDR-TB has been one of the greatest challenges for the Dominican Republic, which was classified by WHO in the mid-1990s as one of the world’s hot spots for MDR-TB.6 This high rate of MDR was associated with poor programme performance and lack of political will to fight the disease. TB control has now been implemented according to internationally recommended guidelines for more than 7 years, and a project to manage MDR-TB has recently started. The use of second-line drugs must be fully supervised to prevent the rise of extensively drug-resistant TB. New data on the magnitude of MDR-TB is urgently needed. In addition, a strengthened national network of properly-equipped laboratories with trained personnel and a fully functioning national reference laboratory are necessary to ensure access to quality-assured sputum smear microscopy, culture and drug-susceptibility testing. Surveillance efforts in the Dominican Republic, although following WHO/PAHO standards, need to be strengthened. While case reporting in DOTS areas suggests a steady increase in the number of cases detected, nationally there is an inconsistent pattern of increases and decreases. The quality of case finding across the country and TB programme/health system issues, such as the quality of the workforce, may be contributing factors explaining disparities. The national TB programme needs to develop and maintain a strong stewardship capacity to guide and oversee collaboration between private and public providers. Public–private approaches, including monitoring and evaluation, should be explored and implemented. Increased advocacy and social mobilization to engage civil society in TB-control efforts is also needed to increase access to DOTS services in urban and rural areas. The implementation of locally relevant operational research can also be useful in identifying programme limitations and strengths, as well as mechanisms to facilitate scaling up of activities. Finally, TB-control efforts must progress hand-in-hand with strengthening of the health system as a whole. International cooperation, financial sustainability and strong political commitment to work at all levels with different stakeholders will be the recipe to achieve targets for TB control in the Dominican Republic. ■

Background: Dizygotic twin pregnancies with discordant manifestation of abnormalities with unclear etiology are of interest because they arise in the same environment. Case report: We present a dizygotic third trimester twin placenta with discordant villous maturation, one placenta lacking developed syncytiocapillary membranes. The twins were eutrophic with no perinatal or postnatal complications. Conclusions: Discordant manifestation of villous maturation in dizygotic twin placentas could be a hint for a genetic rather than an environmental etiology. Villous maturation defect may be underrecognized and has been associated with perinatal morbidity and stillbirth in the late third trimester. Proper recognition is important because of the increased recurrence risk of villous dysmaturity.

Mediators of susceptibility to alcohol-related toxicity in the prenatal environment are relatively unknown. The placenta has been proposed as a potential source of variability in the fetal environment, primarily through its significant metabolic capabilities. Meconium is a toxicological matrix unique to the developing fetus that offers an opportunity to quantify fetal exposure to alcohol through the analysis of fatty acid ethyl esters (FAEE) [nonoxidative ethanol metabolites]. To explore the role of the placenta as a potential source of variability in mediating fetal alcohol exposure via meconium analysis of FAEE, by combining a clinical case report involving human dizygotic twins and a series of guinea pig littermates. Meconium was collected from a pair of dizygotic twins with clinical suspicion of prenatal alcohol exposure and analyzed for FAEE to confirm prenatal alcohol exposure. Meconium was also collected from a series of guinea pig pups prenatally exposed to alcohol at a daily dose of 4 g/kg/day administered to the pregnant dam. FAEE levels were analyzed by gas chromatography with flame ionization detection following liquid-liquid extraction from meconium. The dizygotic twin pair yielded positive meconium FAEE results (>2.00 nmoL/g) in the female twin (2.21 nmoL/g) and no detectable FAEE in the male twin. A total of 15 meconium samples were collected from 15 pups of five pregnant guinea pig litters. With the exception of one pair of littermates, meconium FAEE concentrations differed substantially within each litter (FAEE expressed in units of nmoL/g): litter 1 (0.996, 4.43, 1.36); litter 2 (5.17, 4.15, 0.00); litter 3 (5.16, 5.27); litter 4 (18.57, 8.26, 7.46); litter 5 (0.00, 4.32, 0.00, 1.27). Identical maternal ethanol exposure levels produced differing levels of fetal exposure in a dizygotic human twin pair and a series of guinea pig littermates as evidenced through FAEE meconium analysis. These data indicate that the placenta may have a previously unappreciated role in mediating ethanol-induced fetal injury.

Heteropaternal superfecundation (HP) is the fertilization, within the same cycle, of simultaneously released ova by sperm from separate males. The twin offspring resulting from HP are genetically equivalent to half-siblings, sharing an average of 25% of their genetic complement, by descent. The frequency of such twins is unknown and assumed to be rare, but is likely to be underestimated. Reasons for underestimation include inadequate detection, absence of confirmation, links between illegitimate births and dizygotic twinning, modern reproductive technologies and public unawareness of such pairs. A recently identified case of heteropaternal female twins is illustrative in this regard. HP twins pose significant implications for paternity suits, organ donation and other forensic inquiries. Recognizing the importance of this special class of non-identical twins is further emphasized, given that their inclusion in modest size twin samples might spuriously inflate estimates of genetic influence underlying measured traits.

The purpose of this case presentation is to determine the efficiency of two treatment mechanics in correcting clinically comparable malocclusion in dizygotic twins. The case report describes the orthodontic management of 19-year-old non-identical twins diagnosed with bimaxillary dentoalveolar protrusion on a Class I skeletal base with severe crowding using two different treatment mechanics. The first patient was treated with frictionless mechanics by making use of Kalra simultaneous intrusion and retraction arch for space closure, whereas the friction mechanics accomplished the task in the second patient with mini-implant (Titanium mini-implant, FavAnchor™ SAS, Favorite supplies, Thane west, Maharashtra, India) assisted power arm (Power hook, Azdent Orthodontics, Zhengzhou, China) retraction. It evaluated the overall treatment duration, anterior torque control, and level of comfort for the patients with the two mechanics. The post-treatment results in both cases exhibited remarkable change in inclination of upper anterior teeth which were established through cephalometric findings. Moreover, the anterior torque control was comparatively superior with loop mechanics over mini-implant assisted sliding mechanics. Both the treatment mechanics effectively and efficiently corrected the malocclusion with considerable impact on soft-tissue profile.

IntroductionBrown syndrome is a rare ocular movement abnormality. This syndrome is characterized by an inability to elevate the affected eye in adduction. Most cases are sporadic but the occurrence in Monozygotic twins has suggested the possible autosomal dominant inheritance in Brown syndrome.Case presentationA 4-year-old girl (one pair of dizygotic twins) was referred to our pediatric ophthalmology clinic to assess her abnormal eye movement noticed by her mother. Visual acuity of both eyes was 20/20 with Snellen chart. Ocular motility showed mild exotropia in primary position with marked divergence in upward gaze (V pattern), mild hypotropia in adduction, and limitation of elevation in adduction of both eyes (Fig. 1A). We also examined her sister, all ocular evaluations including visual acuity, slit lamp examination, funduscopy and ocular motility (Ductions & Versions) were normal without any limitation.We also review the related articles that previously have reported Brown syndrome in twins.ConclusionAlthough there are few case reports of Brown syndrome in twins, combination of these reports may elucidate the genetic basis of this disease.

Introduction and importanceThe association in the occurrence of hypertrophic pyloric stenosis (HPS) is 0.25 % to 0.44 % between monozygotic twins and 0.05 % to 0.10 % in dizygotic twins. A combination of genetic and environmental factors may have contributed to the occurrence of HPS. In view of the few related cases reported recently, we present two dizygotic twins who were diagnosed with HPS. Case presentationThis report describes a rare case of congenital infantile hypertrophic pyloric stenosis in preterm dizygotic twins diagnosed early, in which the first case presented with severe clinical features and managed surgically while the second presented with moderate features and hence managed non-operatively with atropine for 14 days. At 6 months of age, both twins continued to tolerate feeds, demonstrated satisfactory weight gain and had achieved appropriate developmental milestones. The postoperative course was uneventful in the twin A. Clinical discussionCongenital HPS in premature twins remains an underdiagnosed pathology due to its clinical picture mimicking digestive intolerance to feeds. The mean age at diagnosis is about 38 days, and only 0.4 % of all children suffering from HPS show symptoms in the first 3 days of life. Symptom relief is achieved after a classic pyloromyotomy is performed by a more preferable laparoscopic technique or using the open surgical technique. ConclusionIf one of the dizygotic twins has HPS, the other baby should be evaluated for the same diagnosis as early as possible, to ensure timely management. HPS with moderate clinical features can be treated with atropine for 14 days while severe HPS should be treated by pyloromyotomy.

To understand a mechanism for the difference in clinical manifestations of congenital cytomegalovirus (CMV) infection between dizygotic twins, the placentas of the dizygotic twins were evaluated for the number of the cells infected with CMV by immunohistochemical and in situ hybridization studies. A Japanese woman with dizygotic twin pregnancy had immunoglobulin M antibodies to CMV at 15 weeks gestation. Intrauterine growth retardation was noted only in the first twin. At birth, CMV was isolated from urine culture in both twins. Clinical manifestations for CMV, such as petechiae, jaundice, hepatosplenomegaly, and deafness were more pronounced in the first twin than in the second twin. Immunohistochemical and in situ hybridization studies showed CMV-positive cells two or three times more densely distributed in the placenta of the first twin compared with the second twin. These data suggest the severity of CMV manifestations of dizygotic twins may be in accord with the number of CMV-positive cells in the placenta.

Binovular follicles including a pair of conjoined oocytes within a common zona pellucida or their fusion in the zonal region gained some attentions due to its possible role in dizygotic twins. Although some cases in the literature been reported in which two conjoined oocytes arising from binovular follicles were mature, and injected with two separated sperm, no available evidence reported for dizygotic twin pregnancies. A case report of a 37-year-old female patient underwent embryo transfer cycle whereby a pair of conjoined blastocysts after ICSI of a pair of conjoined oocytes was transferred. The β-hCG level was positive 15days after embryo transfer. The subsequent pregnancy scan revealed a dizygotic pregnancy. The woman gave birth to two healthy boys in the mid of 38weeks of gestation by cesarean section. Given the insufficient evidence on how to handle conjoined oocytes, this report acknowledges the first occurrence of dizygotic twin delivery resulted from transfer of a pair of conjoined blastocysts after ICSI of a pair of conjoined oocytes. This also confirms that we should be extremely conservative in discarding any mature oocyte without sufficient data about its useless future to result in a healthy baby.

First-born twins are at a four-fold risk of acquiring HIV infection if delivered by caesarean section. A female second twin delivered by caesarean section presented at the age of 14 months with features of HIV/AIDS. She died four months later of full blown AIDS. The first twin, a male, who was delivered vaginally, is asymptomatic and negative for HIV-1 at 18 months of age. He is growing normally. Their father died of AIDS a month before the demise of twin two. Discussion focuses on factors influencing perinatal transmission of HIV and strategies available to minimize the risk. Key Words: HIV, transmission, dizygotic twins. [Jnl College of Medicine Vol.8(2) 2003: 27-30]

A review of the literature concerning “early infantile autism” revealed that very few cases of this syndrome have been reported in twins. For example, such a distinction was not made in Kallman's large scale study of childhood schizophrenia in twins. This case report concerns a set of fraternal female twins who are presented as typical examples of “early infantile autism”. A pregnancy marked by an early threatened abortion was followed by a normal labor and delivery without complications. Early development was normal but before their second birthday they began a gradual withdrawal and loss of most of the speech they had developed. Their subsequent development is traced to their eighth year. The lack of appreciable change in their condition despite vigorous therapeutic efforts is noted. These included placement in a special nursery school, foster home care and psychiatric attention. The latest approach to their difficulty consisting of admission to a children's psychiatric hospital for observation and assessment of their condition is described in some detail. The findings on general physical and neurological examination are described. They were within normal limits aside from a mildly diffusely abnormal E.E.G. in one of the twins. Kanner's clinical picture of autism is related to the symptoms in these children and the close correspondence noted. Continuing, the difficulties in applying psychometric testing to the children is described and the findings concerning the parents are listed. Finally, a picture of the children's behaviour during their stay in hospital, together with a brief description of the methods used to make a tentative analysis of their behaviour, is presented.

In this case report we describe colloid cysts in the third ventricles of monozygotic twin sisters. They were 26 years old when their condition was discovered. One woman was admitted to us on an emergency basis, with signs of high intracranial pressure such as unconsciousness and extension posturing. Her sister was also brought to the hospital since she had a history of attacks of headache. They were both operated with removal of the colloid cysts, and the clinical courses are described in the case report. In reviewing the literature another 30 familial cases were found. Of these were two pairs of monozygotic and one pair of dizygotic twins.