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
Taking over the Atlas
Dear Colleagues,
The Atlas, once more, is in great danger, and I will have to proceed to a collective economic lay-off of all the team involved in the Atlas before the begining of April 2015 (a foundation having suddenly withdrawn its commitment to support the Atlas). I ask you herein if any Scientific Society (a Society of Cytogenetics, of Clinical Genetics, of Hematology, or a Cancer Society, or any other...), any University and/or Hospital, any Charity, or any database would be interested in taking over the Atlas, in whole or in part. If taking charge of the whole lot is too big, a consortium of various actors could be the solution (I am myself trying to find partners). Could you please spread the information, contact the relevant authorities, and find partners.
Survival of the Atlas will be critically dependant upon your ability to find solutions (and urgently!).
Kind regards.
Jean-Loup Huret
Donations are also welcome
If each casual visitor gives 3 Euros or Dollars, the Atlas is saved in a week !
If each professional gives 100 Euros or Dollars once a year (now), the Atlas is saved in 2 weeks !
Don't let the Atlas imminent demise
Note: we send fiscal receipts for donations equal or above 50 Euros or Dollars

Donate (in Euros)

Donate (in US Dollars)


Sotos syndrome (SOS)


Other namesCerebral gigantism
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
    Location 5q35
    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.

    External links

    OrphanetSotos syndrome (SOS)


    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


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


    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 ]
    URL :

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Tue Feb 17 19:42:40 CET 2015

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

    For comments and suggestions or contributions, please contact us