Another case of preaxial polydactyly and white forelock in branchio-oculo-facial syndrome

A 1-year-old male with branchio-oculo-facial syndrome together with preaxial polydatyly and a white forelock at birth is described. This is only the second case where preaxial polydactyly has been described in branchio-oculo-facial syndrome. In both cases a diagnosis of Waardenburg syndrome had been considered.     

Intestinal mucosa on top of a rudimentary occipital meningocele in amniotic rupture sequence: disorganization-like syndrome, homeotic transformation, abnormal surface encounter or endoectodermal adhesion?

We present a case of a peculiar rudimentary occipital meningocele that was surgically removed when the patient (a boy) was 5 months of age. The patient also had distal transverse defects of both hands. The association of congenital scalp defects and distal congenital hand anomalies is relatively rare and one form is known as the Adams-Oliver syndrome. To our surprise, microscopic examination revealed intestinal mucosa on top of the skin tag containing the rudimentary meningocele. No comparable cases were found in the literature. We discuss the following possible explanations for this peculiar situation: 1) disorganization-like syndrome; 2) homeotic transformation; 3) abnormal surface encounter between the epidermis and remnants of the yolk sac or omphalo-enteric duct; and 4) endoectodermal adhesion in the presomite embryo.     

Preaxial polydactyly in neurofibromatosis 1

Although skeletal manifestations are a cardinal feature of neurofibromatosis 1, they are largely confined to the axial skeleton and tibiae. In contrast, congenital malformations of the extremities are less common in patients with neurofibromatosis 1, occurring in fewer than 10%. We describe a boy with bilateral, symmetrical polysyndactyly (preaxial polydactyly type IV) and neurofibromatosis 1. This report discusses peripheral skeletal malformations in neurofibromatosis 1 and their possible etiology.     

Diaphragmatic hernia and preaxial polydactyly in spondylothoracic dysplasia

We report on two cases (male twins), and a female sib terminated at 20 weeks, whose autopsy revealed features of spondylothoracic dysplasia (STD) and also a diaphragmatic hernia and preaxial polydactyly. We present the findings and review STD and the closely related spondylocostal dysostosis. On the basis of the discussion we suggest that our cases are possibly the first report of preaxial polydactyly in spondylothoracic dysplasia and that STD and spondylocostal dysostosis may be allelic.     

Isolated polydactyly: prenatal diagnosis and perinatal outcome

Our objective was to determine the clinical significance of isolated polydactyly identified on prenatal sonogram. All patients with sonographically detected isolated polydactyly scanned over an 11-year period were identified from our database. All patients underwent detailed surveys, and follow-up was obtained by review of the medical records and telephone conversations with parents and referring physicians. Thirteen patients with isolated polydactyly were identified. Follow-up was available in 12 patients. Indications for referral included advanced maternal age (2), second-opinion polydactyly (4), family history of polydactyly (1), uncertain dates (5), and growth (1). The gestational ages at the times of sonographic diagnosis ranged from 17.5 to 34 weeks with all but one case being identified before 23 weeks. Prenatal identification included polydactyly of the upper limb (8), lower limb (4), and both upper and lower limbs (1). Postaxial polydactyly was seen in 12 patients and preaxial in one. Polydactyly was confirmed in all 12 cases in which follow-up was available. Karyotypes were normal in all five fetuses in which amniocentesis was performed. Ten of 12 fetuses were born alive, one died in utero at 34 weeks as a complication of severe pre-eclampsia and one died at term as a result of a cord accident. No surviving neonate had any other identifiable malformation or suspected karyotypic abnormality. In conclusion isolated polydactyly identified by prenatal sonography is associated with good perinatal outcome.     

Bilateral preaxial polydactyly: a possible dominant inheritant

We described families with the preaxial polydactyly in bilateral hands and feet. An analysis of their pedigree strongly suggested that the polydactyly was controlled under the autosomal dominant inheritance. Despite multiple abnormalities, surgical outcomes were quite satisfactory. These cases would be useful for antenatal diagnoses and counseling.     

Optic nerve coloboma, Dandy-Walker malformation, microglossia, tongue hamartomata, cleft palate and apneic spells: an existing oral-facial-digital syndrome or a new variant?

We report on a female infant with postaxial polydactyly of the hands, preaxial polydactyly of the right foot, cleft palate, microglossia and tongue hamartomata consistent with an oral-facial-digital syndrome (OFDS). The patient also had optic nerve colobomata, a Dandy-Walker malformation, micrognathia and apneic spells. This combination of clinical features has not been previously reported. This patient either expands the clinical features of one of the existing OFDS or represents a new variant. A review of the literature highlights the difficulties in making a specific diagnosis because of the different classification systems that exist in the literature.     

Tibial aplasia, lower extremity mirror image polydactyly, brachyphalangy, craniofacial dysmorphism and genital hypoplasia: further delineation and mutational analysis

Congenital anomalies involving tibial aplasia are rare. Recently, four children with an unusual combination of limb anomalies, facial dysmorphism and genital hypoplasia have been reported. All affected children reported were male. One case noted father to son transmission, implying autosomal dominant inheritance. We report the first female patient with this syndrome. The patient had tibial aplasia, mirror image preaxial polydactyly involving her feet, brachyphalangy, genital hypoplasia as well as facial dysmorphism including telecanthus, blepharophimosis, a flat nasal bridge with a small nose and a small mouth. Consistent with reports in males of a micropenis and hypoplastic scrotum, our patient had absent labia minora and a very small clitoris. Her father had very minor anomalies suggestive of somatic mosaicism or marked variability. Mouse models affecting limb development are powerful tools in the study of human syndromes. The clinical phenotype of patients with this syndrome is reminiscent of some luxoid mouse mutants suggesting Alx4 and related members of the paired homeodomain class as candidate genes. ALX4 haploinsufficiency in humans causes parietal foramina, which one patient with this syndrome was reported to have. Sequencing of coding exons of ALX4 and its related homologue, ALX3, in the proband failed to reveal coding sequence alterations. Our father/daughter pair is the second family reported, supporting a dominant mode of inheritance. Moreover, the very mild phenotype in the father suggests the need for very careful attention to parental examination in such cases.     

Amniotic band sequence versus the autosomal recessive microcephaly, facial clefting, and preaxial polydactyly syndrome

We report a Brazilian boy, born to consanguineous parents. On the left arm there was a proximal 'ring shaped' constriction, regional aplasia cutis, and a short hand with markedly hypoplastic fingers and nails 2-3. He also had a bilateral cleft lip/palate, preaxial polydactyly involving the distal phalanx of the left index finger, and a supernumerary nipple on the right. The differential diagnosis is discussed.     

Microcephaly, distinctive facies, single atrium, postaxial polydactyly, skeletal defects and mental retardation: a new familial faciocardiomelic syndrome?

Three siblings with postaxial polydactyly type A, congenital heart defect (single atrium), mental retardation, microcephaly, a distinctive facial appearance, skeletal anomalies and neonatal macrosomy were studied. Comparison with other cardiomelic syndromes previously described in the literature lead us to conclude that this is a new faciocardiomelic syndrome probably inherited as an autosomal recessive trait.     

Fetal polydactyly diagnosis during early pregnancy: clinical applications

OBJECTIVES: This study was undertaken to assess the incidence of fetal polydactyly observed by ultrasonography and to evaluate the outcome of these fetuses. STUDY DESIGN: Detailed ultrasonographic examinations were performed in 17,760 consecutive pregnant women. Both low- and high-risk pregnancies were included in the study. Most examinations were carried out at 14 to 16 weeks' gestation. RESULTS: Twenty-six fetuses with polydactyly were observed. Ten fetuses had either associated anomalies or polydactyly of the feet, or both, and those pregnancies were terminated. The other 16 fetuses had isolated polydactyly and a normal karyotype. Fourteen of them had postaxial polydactyly type B. The outcomes of fetuses with isolated polydactyly were usually favorable. There was 1 intrauterine death and there were 2 terminations of pregnancy. Four infants were born with polydactyly. In utero autoamputation of extra digits occurred in 2 cases, whereas in the remaining infants only a small residual bump was noted. CONCLUSIONS: Isolated fetal postaxial polydactyly type B is associated with a favorable outcome.     

Mullerian agenesis associated with in-utero thalidomide exposure: A case report

Thalidomide is a well-known teratogen, which is experiencing resurgence as new uses are identified. Exposure is classically associated with limb deformities, such as: dysmelia, phocomelia, preaxial hypoplasia and polydactyly, in addition to visceral anomalies that have been documented as well. We report a case of a 38 year-old nulligravid female, who was previously evaluated for primary amenorrhea, and given the presumptive false diagnosis of an imperforate hymen. On magnetic resonance imaging (MRI) exam, she was noted to have uterovaginal agenesis. The implications of thalidomide on women’s health extend beyond external birth defects. Although, most commonly associated with limb deformities, there may also be gynecologic implications of in utero exposure. As this medication is increasingly used for various medical conditions, obstetricians/gynecologists need to remain aware of this potential mullerian teratogenic effect.     

Pre-existing diabetics: Relationship between glycemic control and emotional status in pregnancy

The purpose of this retrospective study was to determine if maternal serum (MSAFP) or amniotic fluid (AF-AFP) α-fetoprotein analysis might he useful in detecting fetal structural defects in the first trimester. During a 5-year period, 20 fetal anomalies were diagnosed at 11–13 weeks by transvaginal ultrasound scanning. A MSAFP sample was obtained in all 20 patients and 17 patients had AF-AFP results obtained by an early amniocentesis. Ten of 20 patients (50%) had elevated MSAFP levels, and 6 or 17 patients had elevated AF-AFP samples (35%). MSAFP was elevated in 4 of 5 cases of anencephaly (80%), in one fetus with the combined malformations of anencephaly and omphalocele, in one fetus with a large encephalocele, in 2 of 3 fetuses (67%) with an omphalocele, and in two cases of cystic hygroma with an abnormal karyotype. AF-AFP was elevated in 3 of 3 cases of anencephaly, in one fetus with the combined defects of anencephaly and omphalocele, in 1 of 3 cases (33%) of omphalocele, and in one fetus with an encephalocele.

Our study suggests that MSAFP and AF-AFP analysis may prove useful in detecting fetal malformations in the first trimester. Larger prospective studies are needed to evaluate further the association of fetal anomalies and first-trimester AFP analysis.     

Antenatal diagnosis of sacral agenesis syndrome in a pregnancy complicated by diabetes mellitus

The sacral agenesis syndrome is a severe congenital abnormality consisting of agenesis of the lumbar spine, sacrum, and coccyx, as well as hypoplasia of the lower extremities. It is considered the most characteristic of all congenital anomalies associated with maternal diabetes mellitus. We describe the sonographic and radiologic findings of agenesis of the lumbosacrococcygeal spine with lower limb and genital hypoplasia in the offspring of a woman with both diabetic retinopathy and nephropathy. The diagnosis was established at 25 weeks' gestation and was confirmed by radiologic evaluation of the neonate.     

The role of ultrasonography and amniocentesis in the evaluation of pregnancies at risk for neural tube defects

To assess the relative efficacy of amniocentesis versus targeted (detailed) ultrasonography, 225 patients referred because of an elevated maternal serum alpha-fetoprotein level (79.6%) or a family history of neural tube defect (20.4%) were evaluated. Ultrasonographic examination alone detected all 26 fetal abnormalities (11 cases of anencephaly, 10 cases of open spina bifida, and five other anomalies). Twenty-eight patients declined amniocentesis; all had normal pregnancy outcomes. Of the 167 patients with apparently normal fetal anatomy by sonography, seven had elevated alpha-fetoprotein levels but no acetylcholinesterase in the amniotic fluid. Six of these pregnancies resulted in normal infants; one infant had congenital nephrosis. The remaining 160 patients had normal sonograms with normal amniotic fluid alpha-fetoprotein levels and no fetal malformations at delivery. Although these results suggest that targeted ultrasonography by experienced personnel is a reasonable alternative to amniocentesis in evaluations for neural tube defects, the availability, cost-effectiveness, and diagnostic accuracy of this approach must be well documented in large prospective studies.     

Amniotic fluid alpha-fetoprotein levels and the prenatal diagnosis of neural tube defects: a collaborative study of 2180 pregnancies in the Netherlands.

Amniotic fluid alpha-fetoprotein (AFP) concentrations were measured in 2180 patients at risk of fetal abnormality because of previous history, family history, advanced maternal age, suspected fetal growth retardation and hydramnios. In 12 patients investigated before 20 weeks gestation, pregnancy was terminated because of a raised amniotic fluid AFP-level: 11 fetuses had neural tube defects (NTDs) and one had a congenital nephrosis. There were no false negative results in the 1927 patients tested before 20 weeks and with a pregnancy of known outcome. In patients tested after 20 weeks, the amniotic fluid AFP concentration was raised in 20 cases of anencephaly, in 9 fetuses with severe congenital malformations without NTD and in one apparently normal fetus. Of 428 patients with a previous offspring who had a NTD, only 8(1.9 per cent) again had a fetus with a NTD.     

70例尸检所见神经管畸形的病理学分析

目的通过病理解剖,了解山西吕梁农村地区神经管畸形的检出率及病理特点.方法对三个县（6个解剖单位）的孕20～28周中期引产胎儿及7 d内死亡围产儿（含死胎、死产及活产儿）,逐一在当地进行详细的尸体解剖,并带回制片做全面镜检.结果70例中发现神经管畸形25例,占尸检的35.7%.其中胎儿为41.5%（17/41）,围产儿为27.6%（8/29）,多为复合畸形.常见的神经管畸形为各种类型的脊柱裂、先天性脑积水、无脑儿及脑膜脑膨出等.结论该地区尸检的畸形检出率明显高于城市,吕梁地区为神经管畸形的高发区.     

Congenital anomalies are an independent risk factor for neonatal morbidity and perinatal mortality in preterm birth

OBJECTIVE: To determine whether congenital anomalies are associated with a high rate of neonatal morbidity in preterm birth. STUDY DESIGN: 312 singletons (22-36 wk) with congenital anomalies that were delivered preterm were compared with a random sample of 936 preterm singleton without congenital anomalies. Data was obtained using the computerized birth discharge records. Statistical analysis included univariate and multivariate logistic regression analyses. RESULTS: Three thousand five hundred and seventy-eight (3578) women with preterm births met the inclusion criteria (singleton with prenatal care). The prevalence of congenital anomalies in the study population was 8.7% (312/3578). Gestational age at delivery was significantly lower in the congenital anomaly group compared with the control (32.0+/-3.7 SD vs. 34.4+/-2.7 SD; p<0.001). The following pregnancy complications were higher in the group with congenital anomalies than in those without anomalies: severe pregnancy induced hypertension (PIH), hydramnions, oligohydramnion, intrauterine growth restriction (IUGR), fetal distress, cesarean section, malpresentation and mal position, abruption placenta, meconium stained amniotic fluid, 1 min Apgar score (<2), 5 min Apgar score (<7). Perinatal mortality rates in 28-32 wk and 33-36 wk were significantly higher in the group with congenital anomalies than in the control group. Neonatal morbidity data (necrotizing enterocolitis, respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage, and sepsis) was available for 909 neonates (239 with congenital anomalies and 670 without congenital anomalies). After adjusting for gestational age, the presence of congenital anomalies remained strongly associated with neonatal morbidity (having one or more of the above mentioned conditions) (adjusted OR: 5.3, 95% CI 3.4-9.2). When adjusting for other confounding variables, congenital anomalies were strongly associated with neonatal morbidity (OR: 6.44, 95% CI 3.94-10.51), and perinatal mortality (OR: 3.08, 95% CI 2.04-4.65). In terms of attributable fraction in our population of preterm births, the proportion of neonatal morbidity and the proportion of perinatal mortality attributable to congenital malformation is 32% and 15%, respectively. CONCLUSION: Congenital anomalies in preterm birth are associated with a higher rate of pregnancy complications and are an independent risk factor for neonatal morbidity and perinatal mortality.     

Ultrasonographic diagnosis of Jarcho-Levin syndrome at 20 weeks' gestation in a fetus without previous family history

Jarcho-Levin syndrome (JLS; spondylothoracic dysplasia) is a congenital disease characterized by multiple vertebral and rib malformations, causing a short trunk dwarfism commonly leading to respiratory insufficiency and death during the first years of life. We describe a case diagnosed during the second trimester routine ultrasound scan for screening of fetal anomalies without a previous family history. The fetus had a severe disorganization of the spine and ribs, skeletal kyphosis, with several hemivertebrae and a small thorax. All of the findings at postmortem examination confirmed the ultrasound features and were consistent with the JLS. To the best of our knowledge there is only one case reported in the literature of a prenatal diagnosis of the syndrome in a family with low risk for the condition.     

Monozygotic twinning as a congenital defect and congenital defects in monozygotic twins

The process of monozygotic twinning in animals and humans is presented. In addition, congenital defects in monozygotic twins versus dizygotic twins and singletons is discussed. Overall, the rates of congenital anomalies are higher among whites as compared to blacks, males as compared to females, and multiples as compared to singletons. The highest rates are among infants born to women in the oldest age category and infants with birth weights below 2,000 g. Among white infants, live births in plural deliveries had 22% more congenital anomalies as compared to single live births. Among black infants, the rate was only 4% higher among multiples. It has been suggested that the more frequent occurrence of low birth weight and preterm delivery among multiple births and by race are critical to the higher incidence of congenital anomalies in twins. Newer theories relating the twinning process to congenital anomalies in twins are also presented.