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Sotos syndrome (SOS)

Written2004-10Kurotaki Naohiro
Department of Molecular, Human Genetics, Baylor College of Medicine, One Baylor Plaza 604B (Lupski lab), Houston, Texas 77030, USA

(Note : for Links provided by Atlas : click)


Other namesCerebral gigantism
Atlas_Id 10045
Genes implicated inNSD1   NFIX  
Inheritance Generally sporadic, a few inherited cases. The familial case reported in 2003 was proved to have NSD1 mutation


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%


    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 NameNSD1 (Nuclear receptor-binding, su (var), enhancer-of-zeste and trithorax domain-containing protein 1
    Alias Nuclear receptor binding SET domain protein 1
    Location 5q35.2
    Note Haploinsufficiency of NSD1 is a major cause of SoS.
    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.
    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.


    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
    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


    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 :

    External links

    OrphanetSotos syndrome
    Other databaseSotos syndrome (GARD)
    Genes implicated inNSD1   [ Atlas ]   [ Entrez ]  [ LOVD ]  [ GeneReviews ]  
    Genes implicated inNFIX   [ Atlas ]   [ Entrez ]  [ LOVD ]  [ GeneReviews ]  

    REVIEW articlesautomatic search in PubMed
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