Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA
 

Sotos syndrome (SOS)

Identity

Other namesCerebral gigantism
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 NameNSD1
    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.

    External links

    OrphanetSotos syndrome (SOS)

    Bibliography

    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
     
    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
     
    Haploinsufficiency of NSD1 causes Sotos syndrome (SOS).
    Kurotaki N, Imaizumi K, Harada N, Masuno M, Kondoh T, Nagai T, Ohashi H, Naritomi K, Tsukahara M, Makita Y, Sugimoto T, Sonoda T, Hasegawa T, Chinen Y, Tomita Ha HA, Kinoshita A, Mizuguchi T, Yoshiura Ki K, Ohta T, Kishino T, Fukushima Y, Niikawa N, Matsumoto N
    Nature genetics. 2002 ; 30 (4) : 365-366.
    PMID 11896389
     
    Familial Sotos syndrome (SOS) is caused by a novel 1 bp deletion of the NSD1 gene.
    Hglund P, Kurotaki N, Kytl S, Miyake N, Somer M, Matsumoto N
    Journal of medical genetics. 2003 ; 40 (1) : 51-54.
    PMID 12525543
     
    Fifty microdeletions among 112 cases of Sotos syndrome (SOS): low copy repeats possibly mediate the common deletion.
    Kurotaki N, Harada N, Shimokawa O, Miyake N, Kawame H, Uetake K, Makita Y, Kondoh T, Ogata T, Hasegawa T, Nagai T, Ozaki T, Touyama M, Shenhav R, Ohashi H, Medne L, Shiihara T, Ohtsu S, Kato Z, Okamoto N, Nishimoto J, Lev D, Miyoshi Y, Ishikiriyama S, Sonoda T, Sakazume S, Fukushima Y, Kurosawa K, Cheng JF, Yoshiura K, Ohta T, Kishino T, Niikawa N, Matsumoto N
    Human mutation. 2003 ; 22 (5) : 378-387.
    PMID 14517949
     
    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) 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
     
    Genetics of Sotos syndrome (SOS).
    Visser R, Matsumoto N
    Current opinion in pediatrics. 2003 ; 15 (6) : 598-606.
    PMID 14631206
     
    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
     
    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.
    Hglund P, Kurotaki N, Kytl S, Miyake N, Somer M, Matsumoto N
    Journal of medical genetics. 2003 ; 40 (1) : 51-54.
    PMID 12525543
     
    Familial Sotos syndrome (SOS) is caused by a novel 1 bp deletion of the NSD1 gene.
    Hglund P, Kurotaki N, Kytl S, Miyake N, Somer M, Matsumoto N
    Journal of medical genetics. 2003 ; 40 (1) : 51-54.
    PMID 12525543
     
    Mutations in NSD1 are responsible for Sotos syndrome (SOS), but are not a frequent finding in other overgrowth phenotypes.
    Trkmen 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
     
    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
     
    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
     
    REVIEW articlesautomatic search in PubMed
    Last year articlesautomatic search in PubMed

    Contributor(s)

    Written10-2004Kurotaki Naohiro
    Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza 604B (Lupski lab), Houston, Texas 77030, USA

    Citation

    This paper should be referenced as such :
    Naohiro, K
    Sotos syndrome
    Atlas Genet Cytogenet Oncol Haematol. 2004;8(4):343-344.
    Free online version   Free pdf version   [Bibliographic record ]
    URL : http://AtlasGeneticsOncology.org/Kprones/SotosID10045.html

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Sat Jun 28 13:34:41 CEST 2014


    Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

    For comments and suggestions or contributions, please contact us

    jlhuret@AtlasGeneticsOncology.org.