Sotos syndrome (SOS)

Identity

Other names	Cerebral gigantism
Atlas_Id	10045
Genes implicated in	NSD1  NFIX
Inheritance	Generally sporadic, a few inherited cases. The familial case reported in 2003 was proved to have NSD1 mutation

Clinics

Phenotype and clinics

Excessive growth, advanced bone age, typical facial gestalt,developmental delay. In infancy growth is rapid, but settles down above the >97th centile in early childhood. The adult height remains close to normal. Large hands and feet Characteristic facial gestalt: macrocephaly (>97th centile), frontal bossing, prognathism, hypertelorism, and antimongoloid slant of the palpebral fissures Occasional hypotonia and delay in motor and language development Cardiac, urogenital, musculoskeletal, and ophthalmologic anomalies are observed.

Neoplastic risk

Relatively high. Neoplasms in SoS are found with a frequency of 2.2-3.9%

Cytogenetics

Inborn conditions

Routine chromosome analysis usually shows normal karyotype. Chromosomal abnormality concering 5q35 were reported. In addition, several chromosomal translocations other than 5q have been published.

Genes involved and Proteins

Gene Name	NSD1
Alias	Nuclear receptor binding SET domain protein 1
Location	5q35
Note	Haploinsufficiency of NSD1 is a major cause of SoS.

Protein
Note	NSD1 contains at least six functional domains (SET[su(var)3-9,enhancer-of-zest,trithorax], PWWP[proline-tryptophan- tryptophan- proline] -I, PWWP-II, PHD-I[plant homeodomain protein-finger], PHD-II, and PHD-III) and ten putative nuclear localization signals, and encodes 2696 amino acids.

Mutations

Note

Among a total of 87 point mutations reported, 56 were proved to be de novo. So far 69 protein truncation mutations and 18 missense mutations were identified in 225 SoS patients. Protein truncation mutations spread through the entire NSD1 coding regions, but missense mutations clustered at a latter half part of NSD1 where most of functional domains are located. In SoS, five missense mutations were identified in the SET domain, three in PHD domains and two in the PWWP domains. Frequencies of microdeletions involving NSD1 are quite different among different populations. In the Japanese population about a half of cases (49/95) had microdeletions, whereas microdeletions are observed only in 9% of cases (9/100) analyzed in European populations.

Bibliography

Growth in Sotos syndrome (SOS).

Agwu JC, Shaw NJ, Kirk J, Chapman S, Ravine D, Cole TR

Archives of disease in childhood. 1999 ; 80 (4) : 339-342.

PMID 10086939

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

Cole TR, Hughes HE

Journal of medical genetics. 1994 ; 31 (1) : 20-32.

PMID 7512144

NSD1 mutations are the major cause of Sotos syndrome (SOS) and occur in some cases of Weaver syndrome but are rare in other overgrowth phenotypes.

Douglas J, Hanks S, Temple IK, Davies S, Murray A, Upadhyaya M, Tomkins S, Hughes HE, Cole TR, Rahman N

American journal of human genetics. 2003 ; 72 (1) : 132-143.

PMID 12464997

Familial Sotos syndrome (SOS) is caused by a novel 1 bp deletion of the NSD1 gene.

Höglund P, Kurotaki N, Kytölä S, Miyake N, Somer M, Matsumoto N

Journal of medical genetics. 2003 ; 40 (1) : 51-54.

PMID 12525543

Two distinct nuclear receptor interaction domains in NSD1, a novel SET protein that exhibits characteristics of both corepressors and coactivators.

Huang N, vom Baur E, Garnier JM, Lerouge T, Vonesch JL, Lutz Y, Chambon P, Losson R

The EMBO journal. 1998 ; 17 (12) : 3398-3412.

PMID 9628876

Molecular characterization of NSD1, a human homologue of the mouse Nsd1 gene.

Kurotaki N, Harada N, Yoshiura K, Sugano S, Niikawa N, Matsumoto N

Gene. 2001 ; 279 (2) : 197-204.

PMID 11733144

Sotos syndrome (SOS) and haploinsufficiency of NSD1: clinical features of intragenic mutations and submicroscopic deletions.

Nagai T, Matsumoto N, Kurotaki N, Harada N, Niikawa N, Ogata T, Imaizumi K, Kurosawa K, Kondoh T, Ohashi H, Tsukahara M, Makita Y, Sugimoto T, Sonoda T, Yokoyama T, Uetake K, Sakazume S, Fukushima Y, Naritomi K

Journal of medical genetics. 2003 ; 40 (4) : 285-289.

PMID 12676901

NSD1 is essential for early post-implantation development and has a catalytically active SET domain.

Rayasam GV, Wendling O, Angrand PO, Mark M, Niederreither K, Song L, Lerouge T, Hager GL, Chambon P, Losson R

The EMBO journal. 2003 ; 22 (12) : 3153-3163.

PMID 12805229

Spectrum of NSD1 mutations in Sotos and Weaver syndromes.

Rio M, Clech L, Amiel J, Faivre L, Lyonnet S, Le Merrer M, Odent S, Lacombe D, Edery P, Brauner R, Raoul O, Gosset P, Prieur M, Vekemans M, Munnich A, Colleaux L, Cormier-Daire V

Journal of medical genetics. 2003 ; 40 (6) : 436-440.

PMID 12807965

CEREBRAL GIGANTISM IN CHILDHOOD. A SYNDROME OF EXCESSIVELY RAPID GROWTH AND ACROMEGALIC FEATURES AND A NONPROGRESSIVE NEUROLOGIC DISORDER.

SOTOS JF, DODGE PR, MUIRHEAD D, CRAWFORD JD, TALBOT NB

The New England journal of medicine. 1964 ; 271 : 109-116.

PMID 14148233

Mutations in NSD1 are responsible for Sotos syndrome (SOS), but are not a frequent finding in other overgrowth phenotypes.

Türkmen S, Gillessen-Kaesbach G, Meinecke P, Albrecht B, Neumann LM, Hesse V, Palanduz S, Balg S, Majewski F, Fuchs S, Zschieschang P, Greiwe M, Mennicke K, Kreuz FR, Dehmel HJ, Rodeck B, Kunze J, Tinschert S, Mundlos S, Horn D

European journal of human genetics : EJHG. 2003 ; 11 (11) : 858-865.

PMID 14571271

Genetics of Sotos syndrome (SOS).

Visser R, Matsumoto N

Current opinion in pediatrics. 2003 ; 15 (6) : 598-606.

PMID 14631206

Citation

This paper should be referenced as such :

Naohiro, K

Sotos syndrome

Atlas Genet Cytogenet Oncol Haematol. 2004;8(4):343-344.

Free journal version : [ pdf ]   [ DOI ]

On line version : http://AtlasGeneticsOncology.org/Tumors/SotosID10045.html

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