Prenatal findings and the genetic diagnosis of fetal overgrowth disorders: Simpson-Golabi-Behmel syndrome, Sotos syndrome, and Beckwith-Wiedemann syndrome

With the advent of prenatal sonography, fetal overgrowth can be easily detected. Prenatal-onset overgrowth can be secondary to normal variants of familial tall stature, familial rapid maturation, diabetic macrosomia, and congenital nesidioblastosis, or prenatal-onset overgrowth can be primary due to pathological overgrowth disorders. This article provides a comprehensive review of the prenatal findings and the genetic diagnosis of some of the pathological prenatal-onset overgrowth disorders, such as Simpson-Golabi-Behmel syndrome, Sotos syndrome, and Beckwith-Wiedemann syndrome.     

Clinical features of NSD1-positive Sotos syndrome

It is 40 years since the first case of Sotos syndrome was reported. For most of the past four decades the diagnosis of Sotos syndrome has been dependent on the subjective evaluation of clinical criteria, primarily whether the facial gestalt is present. The recent identification of NSD1 (Nuclear receptor-binding SET domain containing protein) mutations and deletions in the great majority of Sotos syndrome cases has allowed re-evaluation of defining and associated features of the condition. In this review we will present the clinical features of Sotos syndrome cases with proven abnormalities in NSD1. This has allowed redefinition of Sotos syndrome as a condition characterised by a typical facial gestalt, macrocephaly and learning difficulties. Childhood overgrowth, advanced bone age, cardiac and genitourinary anomalies, neonatal jaundice, neonatal hypotonia, seizures and scoliosis are all fairly common in children with Sotos syndrome. A mutation or microdeletion of NSD1 is diagnostic of Sotos syndrome.     

Sotos syndrome: two cases with severe scoliosis

Two patients with Sotos syndrome who developed a severe scoliosis are described. These cases illustrate the potential to develop significant spinal curvature in Sotos syndrome.     

Perinatal acquired immunodeficiency syndrome

To date in the United States, 41,366 cases of acquired immunodeficiency syndrome (AIDS) have been reported, constituting a major health disaster. As AIDS spreads to the heterosexual population, perinatal hospital areas are seeing increasing numbers of AIDS patients and their families. Many health care workers have had no formal training in caring for these patients, a dilemma now complicated by fear. It is the challenge and responsibility of health care workers today to educate themselves about this disease. Preparation, both philosophically and with a protocol for standard of care, is essential to avoid a crisis in the workplace and to be able to deliver high quality care and support to these patients and their families. This article contains a protocol of care for mothers and infants with AIDS. Recommendations are made for changes in the routine care of the general population, as many cases of AIDS pass through the perinatal areas undetected.     

Phenotypic variability in a three-generation Northern Irish family with Sotos syndrome

Sotos syndrome is an overgrowth disorder with autosomal dominant inheritance caused by mutations and deletions in the nuclear receptor Set domain-containing protein 1 gene. In general, affected individuals have an advanced bone age, macrocephaly, characteristic facial gestalt and learning difficulties. Genotype-phenotype correlations are unclear. Full penetrance is seen and 95% of cases are de novo. Here, we report a three-generation pedigree, with at least eight affected individuals, shown to harbour the nuclear receptor Set domain-containing protein 1 missense mutation c. 6115C>T. To our knowledge, this is the largest Sotos family reported. The observed phenotype is extremely variable, thus highlighting the clinical heterogeneity that may occur.     

Galloway-Mowat syndrome: prenatal ultrasound and perinatal magnetic resonance imaging findings

ObjectiveTo present prenatal ultrasound and perinatal magnetic resonance imaging (MRI) findings of Galloway-Mowat syndrome.Case ReportA 31-year-old woman, gravida 3, para 2, was referred for genetic counseling at 29 weeks of gestation because of abnormal ultrasound findings and a previous child with Galloway-Mowat syndrome. During this pregnancy, microcephaly, intrauterine growth restriction (IUGR), and oligohydramnios were first noted at 27 weeks of gestation. Repeated ultrasounds showed microcephaly, IUGR, and oligohydramnios. MRI performed at 32 weeks of gestation showed reduced sulcation of the brain, pachygyria, poor myelination of the white matter, and cerebellar atrophy. A diagnosis of recurrent Galloway-Mowat syndrome was made. At 40 weeks of gestation, a 2,496-g female baby was delivered with microcephaly, a narrow slopping forehead, epicanthic folds, microphthalmos, a highly arched palate, a small midface, a beaked nose, thin lips, large low-set floppy ears, clenched hands, and arachnodactyly. Postnatal MRI findings were consistent with the prenatal diagnosis. Renal ultrasound showed enlarged bilateral kidneys with increased echogenicity. At the age of 2 weeks, the infant became edematous and developed nephrotic syndrome.ConclusionMicrocephaly, IUGR, and oligohydramnios are significant ultrasound triad of fetal Galloway-Mowat syndrome. Prenatal ultrasound diagnosis of microcephaly, IUGR, and oligohydramnios in late second trimester or in early third trimester should alert clinicians to the possibility of Galloway-Mowat syndrome and prompt a detailed search of abnormal sulcation, cortical gyral maldevelopment, and cerebellar atrophy by fetal ultrafast MRI.     

抗磷脂综合征的围产期抗凝治疗

抗磷脂综合征(APS)是一组以弥漫性动静脉血栓形成、病理妊娠和持续性抗磷脂抗体阳性为特征的综合征。APS能增加复发性流产、早产、死产、子痫前期、胎儿生长受限等妊娠并发症的发生率。不利的妊娠结局和妊娠期血栓形成之间有关联。围产期APS的治疗主要是对症治疗、防止再次发生血栓和病理妊娠。低剂量阿司匹林和肝素能改善APS的妊娠结局。     

Persistent falcine sinus and unilateral renal agenesis in a girl with Sotos syndrome

Sotos syndrome is an overgrowth syndrome characterized by distinctive facial features, developmental delay, and macrocephaly. Here, we present a 10-year-old girl with prenatal and postnatal overgrowth, prominent forehead, pointed chin, and advanced bone age. She also has a persistent falcine sinus in the posterior falx cerebri, patent ductus arteriosus, unilateral renal agenesis, and scoliosis. A pituitary macroadenoma was also found with external compression of the inferior aspect of the optic chiasm. We identified a de novo missense mutation of the NSD1 (nuclear receptor-binding SET domain protein 1) gene in this patient. Computational three-dimensional structural analysis revealed that the NSD1 mutation induced major alterations.     

Perinatal factors associated with the respiratory distress syndrome

Perinatal factors related to the incidence of respiratory distress syndrome were analyzed by the multiple logistic regression statistical method in 263 mothers and their 298 offspring delivered between 24 and 35 weeks' gestation in a 1-year period in a regional referral perinatal center. The risk of respiratory distress syndrome in white infants rose with decreasing gestational age (p less than 0.0001) while prolonged rupture of membranes of greater than 24 hours in the absence of maternal infection (28% of cases) was highly protective (p less than 0.0001). Compared with vaginal delivery, cesarean delivery without labor increased the risk of respiratory distress syndrome (p = 0.03). The administration of tocolytic drugs was unrelated to the incidence of respiratory distress syndrome, but corticosteroid therapy given at least 72 hours before delivery was protective (p = 0.03). Male and female infants were equally at risk for respiratory distress syndrome as were black and white infants, but other races had a lower incidence (p = 0.004). Infants with respiratory distress syndrome were on mechanical ventilators longer than those with other respiratory illnesses.     

Prenatal ultrasound and magnetic resonance imaging in fetal varicella syndrome: correlation with pathology findings

OBJECTIVES: To assess the diagnostic value of prenatal magnetic resonance imaging (MRI) in addition to prenatal ultrasound in a case of fetal varicella syndrome. METHODS: Comparison of prenatal ultrasound and MRI features obtained at 26 and 32 weeks, respectively, with neonatal imaging (ultrasound, MRI and CT) and macroscopic and microscopic pathology findings in a fatal case of varicella embryopathy. RESULTS: Prenatal ultrasound correlated fairly well with neonatal imaging and pathology findings. Most lesions of thoracic, abdominal and retroperitoneal viscera, limb involvement and even dermatologic features were apparent on ultrasonography. Involvement of the CNS, including cerebellar hypoplasia, was not apparent on ultrasound examination, but was clearly demonstrated by prenatal MRI. CONCLUSION: If maternal seroconversion for the varicella-zoster virus is suspected, combining prenatal ultrasound and magnetic resonance imaging may document the extent of tissue damage in fetal varicella syndrome to a larger extent than has been reported until now and therefore contribute to due counselling following maternal varicella exposure.