Sotos syndrome: a study of the diagnostic criteria and natural history.

Cole, Trevor; Hughes, Helen E.

doi:10.1136/jmg.31.1.20

Cited by 289 publications

(316 citation statements)

References 50 publications

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“…This is consistent with the fact that, throughout childhood and early adolescence, the height was usually more significantly increased than weight in Sotos patients. 15 In addition, our patients did not show respiratory difficulties, one of specific features in Marshall-Smith syndrome, which cause early death in the neonatal period or early infancy. 7 Thus missense mutations in the DNAbinding/dimerization domain, which may lead to loss of transcriptional regulation by NFIX protein, could cause Sotos-like syndrome in two patients.…”

Section: Discussionmentioning

confidence: 47%

Missense mutations in the DNA-binding/dimerization domain of NFIX cause Sotos-like features

Yoneda

Saitsu

Touyama³

et al. 2012

J Hum Genet

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Sotos syndrome is characterized by prenatal and postnatal overgrowth, characteristic craniofacial features and mental retardation. Haploinsufficiency of NSD1 causes Sotos syndrome. Recently, two microdeletions encompassing Nuclear Factor I-X (NFIX) and a nonsense mutation in NFIX have been found in three individuals with Sotos-like overgrowth features, suggesting possible involvements of NFIX abnormalities in Sotos-like features. Interestingly, seven frameshift and two splice site mutations in NFIX have also been found in nine individuals with Marshall-Smith syndrome. In this study, 48 individuals who were suspected as Sotos syndrome but showing no NSD1 abnormalities were examined for NFIX mutations by high-resolution melt analysis. We identified two heterozygous missense mutations in the DNA-binding/dimerization domain of the NFIX protein. Both mutations occurred at evolutionally conserved amino acids. The c.179T4C (p.Leu60Pro) mutation occurred de novo and the c.362G4C (p.Arg121Pro) mutation was inherited from possibly affected mother. Both mutations were absent in 250 healthy Japanese controls. Our study revealed that missense mutations in NFIX were able to cause Sotos-like features. Mutations in DNA-binding/dimerization domain of NFIX protein also suggest that the transcriptional regulation is abnormally fluctuated because of NFIX abnormalities. In individuals with Sotos-like features unrelated to NSD1 changes, genetic testing of NFIX should be considered.

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Section: Discussionmentioning

confidence: 47%

Missense mutations in the DNA-binding/dimerization domain of NFIX cause Sotos-like features

Yoneda

Saitsu

Touyama³

et al. 2012

J Hum Genet

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“…The patients were seen by at least two clinical geneticists involved in this study (DGM, AXA, MAAS and JMPN). Only those patients with unambiguous classic Sotos syndrome 6 were included in this study. The neuroimaging of the eight patients was performed by magnetic resonance imaging (MRI) scans, which were visually inspected by two of the authors (ACS and JDVC), and the identified anomalies were tabulated.…”

Section: Methodsmentioning

confidence: 99%

“…There have also been some benign tumors, including cavernous hemangioma, hairy pigmented nevus and osteochondrome 12,13 . Affected individuals are fertile and there is no evidence that life span is shortened 6 . The other important consideration is the risk of transmission.…”

mentioning

confidence: 99%

“…Head circumference is almost invariably large at birth, and generally proceeds above the 97 th percentile throughout growth 5 . Distinctive craniofacial anomalies include dolichocephaly, prominent forehead, hypertelorism or telecanthus, epicanthic folds, flat nasal bridge, downslanting palpebral fissures, high arched palate, premature eruption of teeth and pointed chin 6 . Other features include cerebellar nystagmus, strabismus, pes planus, kyphoscoliosis, unequal lower limb length, syndactyly, large hands and feet, abnormal dermatoglyphics, functional megacolon and hemihypertrophy.…”

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confidence: 99%

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Sotos syndrome (cerebral gigantism): analysis of 8 cases

Melo

Acosta

Salles

et al. 2002

Arq. Neuro-Psiquiatr.

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“…Sotos syndrome (SoS, OMIM#117550) is a congenital overgrowth syndrome with characteristic craniofacial features and variable degrees of developmental delay (Cole and Hughes 1994). Aberrations of the nuclear receptor binding SET domain containing protein 1 (NSD1) gene at 5q35 include intragenic mutations and submicroscopic whole-gene deletions (Kurotaki et al 2002Douglas et al 2003;Nagai et al 2003;Rio et al 2003;Turkmen et al 2003;de Boer et al 2004;Tatton-Brown et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Analysis of the NSD1 promoter region in patients with a Sotos syndrome phenotype

et al. 2005

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Sotos syndrome (SoS, OMIM#117550) is an overgrowth disorder characterized by excessive growth-especially in the first years of childhood-distinctive craniofacial features, and various degrees of mental retardation. Haploinsufficiency of the nuclear receptor binding SET domain containing protein 1 (NSD1) gene, due to either intragenic mutations or whole-gene microdeletions, is found in the majority of patients with SoS. However, in approximately 10-40% of patients with a typical SoS phenotype, no abnormalities are detected. In this study, hemizygous hypermethylation or genomic sequence abnormalities of the promoter region of NSD1 were hypothesized to be the underlying cause in patients with a SoS phenotype, but without confirmed NSD1 alterations. In 18 patients, including one patient with a reported hepatocellular carcinoma, the promoter region of NSD1 was analyzed.However, no hypermethylation or sequence abnormalities in the promoter region could be detected. It therefore seems unlikely that such abnormalities of NSD1 are a major culprit in patients with phenotypical SoS. Additional methods are necessary for detection of other genetic or epigenetic causes of SoS.

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Sotos syndrome: a study of the diagnostic criteria and natural history.

Cited by 289 publications

References 50 publications

Missense mutations in the DNA-binding/dimerization domain of NFIX cause Sotos-like features

Missense mutations in the DNA-binding/dimerization domain of NFIX cause Sotos-like features

Sotos syndrome (cerebral gigantism): analysis of 8 cases

Analysis of the NSD1 promoter region in patients with a Sotos syndrome phenotype

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