Sotos Syndrome


Sotos syndrome (OMIM #117550) is a childhood overgrowth syndrome with distinctive craniofacial features and mental retardation. Sotos syndrome is caused by haploinsufficiency of the nuclear receptor SET domain containing protein 1 gene (NSD1) located at 5q35.2‐q35.3. A wide variety of NSD1 aberrations have been found: microdeletions, intragenic deletions and missense and truncation mutations. Through in‐depth analyses of microdeletions, low copy repeat (LCR) or Alu‐mediated rearrangements were demonstrated to be major mechanisms for de novo deletions. Therefore, Sotos syndrome is now considered as a genomic disorder. NSD1 is a protein with histone methyltransferase activity and nuclear receptor‐binding capability, both related to transcriptional controls. As pathophysiology regarding abnormalities of NSD1 protein remains unknown, further functional studies are necessary.

Key concepts

  • Haploinsufficiency of NSD1 causes Sotos syndrome.

  • Sotos syndrome is a genomic disorder.

  • Microdeletion involving NSD1 occurs through nonallelic homologous recombination mediated by low copy repeats or Alu elements.

  • NSD1 has specific histone methyltransferase activity.

Keywords: overgrowth syndrome; NSD1; microdeletion; point mutation; histone methyltransferase activity

Figure 1.

Facial appearance of Sotos syndrome. A Japanese girl carrying a whole NSD1 gene microdeletion at the age of two months (left) and at three years (right). Photographs were originally provided by Dr. Nobuhiko Okamoto at the Department of Planning and Research, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Japan, and reproduced by permission of Oxford University Press from Visser R and Matsumoto N (in press) NSD1 and Sotos syndrome. In: Inborn Errors of Development, 2nd edn, chap. 113.

Figure 2.

Low copy repeats associated with Sotos syndrome. Proximal low copy repeat (PLCR) contains eight different blocks (A–H) and distal LCR (DLCR) possesses nine blocks (A–H including two Bs). The most common microdeletion between PLCR‐B and DLCR‐2B is presented.

Figure 3.

NSD1 and its functional domains. SET, su(var) 3‐9, enhancer of zeste, trithorax domain; SAC, SET‐associated Cys‐rich domain; PWWP, proline‐tryptophan‐tryptophan‐proline domain; PHD, zinc‐finger plant homeodomain and NID, nuclear receptor interaction domain.



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Further Reading

Kurotaki N and Matsumoto N (2006) Sotos syndrome. In: Lupski JR and Stankiewicz P (eds) Genomic Disorders: The Genomic Basis of Disease, pp. 237–246. Totowa: Humana Press.

Kurotaki N, Stankiewicz P, Wakui K et al. (2005) Sotos syndrome common deletion is mediated by directly oriented subunits within inverted Sos‐REP low‐copy repeats. Human Molecular Genetics 14: 535–542.

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How to Cite close
Niikawa, Norio, Miyake, Noriko, and Matsumoto, Naomichi(Dec 2008) Sotos Syndrome. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0021430]