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Genetics Home Reference: your guide to understanding genetic conditions
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Sotos syndrome

Reviewed June 2006

What is Sotos syndrome?

Sotos syndrome is a disorder characterized by a distinctive facial appearance, overgrowth in childhood, and learning disabilities or delayed development. Characteristic facial features include a long, narrow face; a high forehead; flushed (reddened) cheeks; and a small, pointed chin. In addition, the outside corners of the eyes may point downward (down-slanting palpebral fissures). This facial appearance is most notable in early childhood. Affected infants and children tend to grow quickly; they are significantly taller than their siblings and peers and have an unusually large head. Adult height is usually in the normal range, however.

People with Sotos syndrome often have intellectual impairment, and most also have behavioral problems. Frequent behavioral issues include attention deficit hyperactivity disorder (ADHD), phobias, obsessions and compulsions, tantrums, and impulsive behaviors. Problems with speech and language are also common. Affected individuals often have problems with sound production, stuttering, and a monotone voice. Additionally, weak muscle tone (hypotonia) may delay other aspects of early development, particularly motor skills such as sitting and crawling.

Other signs and symptoms of Sotos syndrome can include an abnormal side-to-side curvature of the spine (scoliosis), seizures, heart or kidney defects, hearing loss, and problems with vision. Some infants with this disorder experience yellowing of the skin and whites of the eyes (jaundice) and poor feeding. A few people with Sotos syndrome have developed cancer, most often in childhood, but no single form of cancer has been associated with this condition. It remains uncertain whether Sotos syndrome increases the risk of specific types of cancer. If people with this disorder have any increased cancer risk, their risk is only slightly greater than that of the general population.

How common is Sotos syndrome?

Sotos syndrome is reported to occur in 1 in 10,000 to 14,000 newborns. Many cases of this disorder are not diagnosed, however, so the true incidence may be closer to 1 in 5,000.

What genes are related to Sotos syndrome?

Mutations in the NSD1 gene cause Sotos syndrome.

The NSD1 gene provides instructions for making a protein that is involved in normal growth and development. The function of this protein is unknown, however. In the Japanese population, the most common genetic change leading to Sotos syndrome deletes genetic material from the region of chromosome 5 containing the NSD1 gene. In other populations, small mutations within the NSD1 gene occur more frequently. Genetic changes involving the NSD1 gene prevent one copy of the gene from producing any functional protein. It is unclear how a reduced amount of this protein during development leads to learning disabilities, overgrowth, and the other features of Sotos syndrome.

Related Gene(s)

Changes in this gene are associated with Sotos syndrome.

  • NSD1

How do people inherit Sotos syndrome?

About 95 percent of Sotos syndrome cases occur in people with no history of the disorder in their family. Most of these cases result from new mutations involving the NSD1 gene.

A few families have been described with more than one affected family member. These cases helped researchers determine that Sotos syndrome has an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder.

Where can I find information about diagnosis or management of Sotos syndrome?

These resources address the diagnosis or management of Sotos syndrome and may include treatment providers.

  • Gene Review: Sotos Syndrome (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=sotos)
  • Genetic Testing Registry: Sotos' syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0175695)
  • MedlinePlus Encyclopedia: Increased head circumference (http://www.nlm.nih.gov/medlineplus/ency/article/003305.htm)

You might also find information on the diagnosis or management of Sotos syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/sotos-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/sotos-syndrome/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about Sotos syndrome?

You may find the following resources about Sotos syndrome helpful. These materials are written for the general public.

  • MedlinePlus - Health information

    • Encyclopedia: Increased head circumference (http://www.nlm.nih.gov/medlineplus/ency/article/003305.htm)
    • Health Topic: Craniofacial Abnormalities (http://www.nlm.nih.gov/medlineplus/craniofacialabnormalities.html)
    • Health Topic: Growth Disorders (http://www.nlm.nih.gov/medlineplus/growthdisorders.html)
  • Genetic and Rare Diseases Information Center - Information about genetic conditions and rare diseases (http://rarediseases.info.nih.gov/gard/10091/resources/resources/1)
  • Additional NIH Resources - National Institutes of Health
    National Institute of Neurological Disorders and Stroke (http://www.ninds.nih.gov/disorders/sotos/sotos.htm)

  • Educational resources - Information pages

    • Madisons Foundation (http://www.madisonsfoundation.org/index.php?option=com_mpower&task=disease&diseaseID=204)
    • Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=821)

  • Patient support - For patients and families

    • National Organization for Rare Disorders (http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/271/viewAbstract)
    • Resource list from the University of Kansas Medical Center (http://www.kumc.edu/gec/support/sotos.html)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

  • Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=sotos)

  • Genetic Testing Registry - Repository of genetic test information

    • Genetic Testing Registry: Sotos' syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0175695)
  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=(Abnormalities,%20Multiple%5BMAJR%5D)%20AND%20((sotos%20syndrome%5BTIAB%5D)%20OR%20(cerebral%20gigantism%5BTIAB%5D)%20OR%20(sotos%20sequence%5BTIAB%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)
  • OMIM - Genetic disorder catalog (http://omim.org/entry/117550)

What other names do people use for Sotos syndrome?

  • Cerebral gigantism
  • Sotos sequence
  • Sotos' syndrome

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Sotos syndrome?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding Sotos syndrome?

ADHD ; attention deficit hyperactivity disorder ; autosomal ; autosomal dominant ; cancer ; cell ; chromosome ; contiguous ; deletion ; gene ; gigantism ; hyperactivity ; hypotonia ; incidence ; inheritance ; jaundice ; kidney ; motor ; muscle tone ; pattern of inheritance ; population ; protein ; scoliosis ; syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Ball LJ, Sullivan MD, Dulany S, Stading K, Schaefer GB. Speech-language characteristics of children with Sotos syndrome. Am J Med Genet A. 2005 Aug 1;136A(4):363-7. (http://www.ncbi.nlm.nih.gov/pubmed/16001444?dopt=Abstract)
  • Baujat G, Rio M, Rossignol S, Sanlaville D, Lyonnet S, Le Merrer M, Munnich A, Gicquel C, Colleaux L, Cormier-Daire V. Clinical and molecular overlap in overgrowth syndromes. Am J Med Genet C Semin Med Genet. 2005 Aug 15;137C(1):4-11. Erratum in: Am J Med Genet C Semin Med Genet. 2006 Feb 15;142(1):59. (http://www.ncbi.nlm.nih.gov/pubmed/16010674?dopt=Abstract)
  • Cecconi M, Forzano F, Milani D, Cavani S, Baldo C, Selicorni A, Pantaleoni C, Silengo M, Ferrero GB, Scarano G, Della Monica M, Fischetto R, Grammatico P, Majore S, Zampino G, Memo L, Cordisco EL, Neri G, Pierluigi M, Bricarelli FD, Grasso M, Faravelli F. Mutation analysis of the NSD1 gene in a group of 59 patients with congenital overgrowth. Am J Med Genet A. 2005 Apr 30;134(3):247-53. (http://www.ncbi.nlm.nih.gov/pubmed/15742365?dopt=Abstract)
  • Douglas J, Hanks S, Temple IK, Davies S, Murray A, Upadhyaya M, Tomkins S, Hughes HE, Cole TR, Rahman N. NSD1 mutations are the major cause of Sotos syndrome and occur in some cases of Weaver syndrome but are rare in other overgrowth phenotypes. Am J Hum Genet. 2003 Jan;72(1):132-43. Epub 2002 Dec 2. (http://www.ncbi.nlm.nih.gov/pubmed/12464997?dopt=Abstract)
  • Faravelli F. NSD1 mutations in Sotos syndrome. Am J Med Genet C Semin Med Genet. 2005 Aug 15;137C(1):24-31. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16010675?dopt=Abstract)
  • Gene Review: Sotos Syndrome (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=sotos)
  • Lapunzina P. Risk of tumorigenesis in overgrowth syndromes: a comprehensive review. Am J Med Genet C Semin Med Genet. 2005 Aug 15;137C(1):53-71. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16010678?dopt=Abstract)
  • Niikawa N. Molecular basis of Sotos syndrome. Horm Res. 2004;62 Suppl 3:60-5. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15539801?dopt=Abstract)
  • Opitz JM, Weaver DW, Reynolds JF Jr. The syndromes of Sotos and Weaver: reports and review. Am J Med Genet. 1998 Oct 2;79(4):294-304. Review. (http://www.ncbi.nlm.nih.gov/pubmed/9781911?dopt=Abstract)
  • Tatton-Brown K, Douglas J, Coleman K, Baujat G, Cole TR, Das S, Horn D, Hughes HE, Temple IK, Faravelli F, Waggoner D, Turkmen S, Cormier-Daire V, Irrthum A, Rahman N; Childhood Overgrowth Collaboration. Genotype-phenotype associations in Sotos syndrome: an analysis of 266 individuals with NSD1 aberrations. Am J Hum Genet. 2005 Aug;77(2):193-204. Epub 2005 Jun 7. (http://www.ncbi.nlm.nih.gov/pubmed/15942875?dopt=Abstract)
  • Tatton-Brown K, Rahman N. Clinical features of NSD1-positive Sotos syndrome. Clin Dysmorphol. 2004 Oct;13(4):199-204. (http://www.ncbi.nlm.nih.gov/pubmed/15365454?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: June 2006
Published: May 13, 2013