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Simpson–Golabi–Behmel Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Simpson–Golabi–Behmel syndrome (SGBS) is a rare, X-linked, congenital overgrowth disorder characterized by pre/postnatal macrosomia, distinctive craniofacies (e.g., macrocephaly, ocular hypertelorism [widely spaced eyes], macrostomia [unusually large mouth], macroglossia [large tongue with a deep groove or furrow down the middle], broad nose with an upturned tip, palatal abnormalities), organomegaly (often involving the kidneys, liver, or spleen), skeletal anomalies (e.g., vertebral fusion, scoliosis, rib anomalies, and congenital hip dislocation), hand anomalies (e.g., large hands and postaxial polydactyly), supernumerary nipples, diastasis recti (an abnormal opening in the muscle covering the abdomen), umbilical hernia (a soft out-pouching around the navel), congenital heart defects, diaphragmatic hernia (a hole in the diaphragm), genitourinary defects, gastrointestinal anomalies, mild to severe intellectual disability, early motor milestones, and speech delay as well as 10% risk of developing for embryonal tumors (e.g., Wilms tumor, hepatoblastoma, adrenal neuroblastoma, gonadoblastoma, hepatocellular carcinoma, and medulloblastoma) in early childhood [1,2].
Oral and craniofacial disorders
Published in Angus Clarke, Alex Murray, Julian Sampson, Harper's Practical Genetic Counselling, 2019
Characteristic features of the most common form (type I) are clefting of the jaw and tongue, with digital abnormalities (usually syndactyly) and sometimes mental retardation. Renal cysts may occur and almost all cases are female, suggesting X-linked dominant inheritance lethal in the male (see Chapter 2). Mutation in the OFD1 gene is responsible, also known as CXORF5; this is the same gene as that for the Simpson-Golabi-Behmel syndrome. A risk of 50% for female offspring of an affected individual should be given. An extremely rare form (type 2 or Mohr syndrome) following autosomal recessive inheritance, and which is clinically distinguishable, has been described. There have been at least 11 other clinical entities proposed within the OFD syndromes, but this group of conditions may benefit from a careful reassessment of the current system of classification. There is substantial clinical and molecular heterogeneity, and there are many phenotypic overlaps with another group of ‘difficult-to-classify’ conditions, the ciliopathies. A consensus approach is likely to emerge as the results of clinical and molecular studies are integrated.
Idiopathic polyhydramnios and foetal macrosomia in the absence of maternal diabetes: clinical vigilance for costello syndrome
Published in Journal of Obstetrics and Gynaecology, 2022
Costello syndrome is a rare disorder with intellectual disability, characterised by failure to thrive, short stature, joint laxity, soft skin, and distinctive facial features (Hennekam 2003). This syndrome shows significant clinical overlap with Noonan syndrome, and belongs to the RASopathies, a group of conditions resulting from germline variants affecting the RAS-mitogen activated protein kinase pathway. The p.G12A of HRAS gene in our case is a recurrent variant. Indeed, almost all variants affect either codon 12 or 13 of the protein product, with G12S and G12A occurring in 90.9–95.0% of variant‐positive patients (Rauen 2007; Gripp et al. 2019). Foetal overgrowth and polyhydramios were prominent in our case. Prenatal overgrowth syndromes include relatively few conditions, that is, Sotos syndrome, Simpson–Golabi–Behmel syndrome, Beckwith–Wiedemann syndrome, and Costello syndrome. Sotos syndrome is caused by a deletion or mutation in the NSD1 gene, which maps to 5q35 (Faravelli 2005). Foetuses with Sotos syndrome may manifest with increased NT, macrocephaly, polyhydramnios, foetal overgrowth, renal abnormalities, and central nervous system abnormalities (Thomas and Lemire 2008). Simpson-Golabi-Behmel syndrome is an X-linked recessive disorder with variants of CXORF5 or GPC3 gene on chromosome X (Magini et al. 2016). Foetuses may present with macrosomia, polyhydramnios, cystic hygroma, hydrops fetalis, increased nuchal translucency (NT), craniofacial abnormalities, visceromegaly, renal anomalies, congenital diaphragmatic hernia, polydactyly, and a single umbilical artery. Beckwith-Wiedemann syndrome is an imprinting disorder with the region 11p15 involved. Foetuses may manifest with macrosomia, polyhydramnios, macroglossia, omphalocele, placentomegaly, a long umbilical cord, echogenic kidneys, and pancreatic cystic dysplasia (Barisic et al. 2018; Shieh et al. 2019). Since these syndromes are rare, an increased awareness of them among obstetricians will improve their prenatal detection rates.
Synchronous Hepatoblastoma and Neuroblastoma in Two Chinese Infants
Published in Fetal and Pediatric Pathology, 2023
Bo Shao, Yi-zhen Wang, Yuan Fang, Jing Chu, Lian Chen, Le-Jian He
The majority of cancers result from multiple genetic and epigenetic alterations in somatic cells, whereas the minority are caused by germline mutations. The presence of significant genetic disorders was suspected in the synchronous tumors. In previous studies, up to 10% of cancer cases that occur in children were related to known predisposing genetic syndromes [8]. Genetic syndromes were associated with 15% of HBL, while familial NBL occurs only in <5% of cases [9,10]. Genetic syndromes were considered as a possible factor in our cases of synchronous HBL and NBL. The most common associated genetic syndromes with HBL and NBL include Beckwith–Wiedemann syndrome, Simpson–Golabi–Behmel syndrome type 1, familial adenomatous polyposis syndrome, and Li–Fraumeni syndrome. None of the patients had clinical, family history, or genetic evidence to explain the association of synchronous HBL and NBL with known sporadic or hereditary tumor syndromes. In the previous publications, one patient and his twin brother were heterozygous for a p.L444P mutation in the GBA1 [6]. The p.L444P mutation (also known as c.1448T.C), was located in exon 10 of gene locus 1q21 and was associated with Gaucher disease (GD). It was speculated that synchronous tumors might be a novel clinical syndrome mediated by GBA1 mutations. Another patient had a novel germline insertion variant in TWIST1 (p. Gly86dup), along with the potentially pathogenic missense variants in NF1 (p. Val2511Ile), RAF1 (p. Leu445Arg), and WHSC1 (p. Ser4Asn), detected by whole exome sequencing (WES) [7]. Studies revealed that TWIST1, RAF1, and WHSC1 were related to NBL, while NF1 was related both with NBL and HBL [11–15]. Germline mutations in these genes may contribute to the development of synchronous tumors according to the findings [7]. In our case 1, inherited disease (2742 genes) gene test of the patient and his family did not find any pathogenic or likely pathologenic variation in the genes related to the current clinical symptoms. We speculated that synchronous tumors might be related to in vitro fertilization-assisted pregnancy, premature delivery, and low birth weight. At present, the mechanism of synchronous HBL and NBL remains unclear, which deserves further study.