China
Africa
Explore chapters and articles related to this topic
Fascial Stretch Therapy™
Published in David Lesondak, Angeli Maun Akey, Fascia, Function, and Medical Applications, 2020
Sotos Syndrome is a genetic disorder which can occur from the mutation of the NSD1 gene, or the absence of a gene. Primarily, the mutation is most common, and it is passed down from the carrier parent(s). People that are carriers of Sotos Syndrome are 50% likely to pass it on to their offspring.
Sotos Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Confirmation of Sotos syndrome relies on molecular identification of a heterozygous NSD1 pathogenic variant, which is found in at least 90% of affected individuals. Typically, molecular testing is undertaken on the basis of single-gene and/or multigene panel.
The Human Genome Project and Its Impact on Understanding Developmental Disabilities
Published in Merlin G. Butler, F. John Meaney, Genetics of Developmental Disabilities, 2019
Daniel J. Wattendorf, Maximilian Muenke
The acquisition of the BAC (26) and its mapping to human chromosomes provided uses other than a step towards sequence fidelity (27). Many developmental disabilities can now be diagnosed by fluorescent in situ hybridization (FISH) originally developed in 1980 (28). The most common probe used in FISH experiments is a BAC that has been labeled with a fluorescent molecule (Fig. 2). Specific BACs that have been used as part of the HGP can now be used as probes to identify specific causes of developmental disability and are especially useful for screening for deletions. For example, contiguous gene deletions at 7q11.23 cause Williams–Beuren syndrome, a neurodevelopmental disorder characterized by auditory and language strengths with severe visuospatial deficits, characteristic facial dysmorphism, elastin arteriopathy, and a stereotypic behavioral profile of overfriendliness, anxiety, and decreased attention (29) (Fig. 1K). Gene duplications may also be detected by FISH. Pelizaeus-Merzbacher disease is a disorder of dysmyelination of the central nervous system (CNS). It is caused by mutations or duplications of the proteolipid protein (PLP) gene at Xq22. A duplication of a FISH probe containing PLP can be seen in interphase cells (30). Or, in a patient with developmental delay of unknown cause found to have a balanced translocation by routine chromosome analysis, the selection of a series of BACs from the human genome databases may be used to probe across the translocation breakpoint and potentially clone a gene disrupted by this breakpoint. This has recently been demonstrated by the isolation of the NSD1 gene as a cause of Sotos syndrome (31).
Next-generation sequencing and the impact on prenatal diagnosis
Published in Expert Review of Molecular Diagnostics, 2018
Rhiannon Mellis, Natalie Chandler, Lyn S Chitty
The potential benefits of fetal exome sequencing are vast, but there are challenges to overcome before it can enter widespread clinical use. One difficulty, as mentioned above, is the fact that prenatal phenotypes are often incomplete and difficult to interpret. Data generated from fetal exomes will in itself help to address this problem but in the meantime it poses a challenge for interpretation of variants detected, and we must be wary of both over and underreporting of new variants as a result. For example, Sotos syndrome – caused by haploinsufficiency of the NSD1 gene – is an overgrowth syndrome characterized by macrocephaly and intellectual disability and is rarely diagnosed prenatally. However, a recent case was reported of a fetus with microcephaly and intrauterine growth restriction, where fetal genomic analysis revealed a de novo deletion of NSD1 [48]. In this case the pregnancy was terminated but we have now encountered a similar case in a local study, where an NSD1 variant was identified in a microcephalic growth-restricted fetus but could not be classified as pathogenic at the time due to insufficient evidence relevant to the fetal phenotype. Postnatally, the infant subsequently developed macrocephaly and is now reported to have clinical features of Sotos syndrome. This may indicate a previously unrecognized evolving phenotype and highlights the importance of sharing information about new genotype–phenotype associations as cases like these arise.
Non-convulsive status epilepticus in Sotos syndrome: rare first presentation in a rare syndrome
Published in International Journal of Neuroscience, 2023
Christine Ragaie, Nirmeen A Kishk, Amani M. Nawito, Alshimaa S. Othman, Rehab Magdy
Sotos syndrome, previously known as “cerebral gigantism,” is a childhood overgrowth syndrome caused by nuclear receptor set domain-containing protein 1 gene (NSD1) mutations [1]. It is characterized mainly by a prenatal and postnatal overgrowth, distinctive facial appearance and developmental delay with an estimated prevalence of between 1 in 10,000 and 1 in 50,000 [2]. Other features include scoliosis in 30%, congenital heart defects in 8%, and genitourinary anomalies in 15% of cases [3]. Polyhydramnios & other perinatal imaging abnormalities were also reported [4].
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.