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Genetics Home Reference: your guide to understanding genetic conditions
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Short stature, hyperextensibility, hernia, ocular depression, Rieger anomaly, and teething delay

(often shortened to SHORT syndrome)
Reviewed December 2013

What is SHORT syndrome?

Short stature, hyperextensibility, hernia, ocular depression, Rieger anomaly, and teething delay, commonly known by the acronym SHORT syndrome, is a rare disorder that affects many parts of the body.

Most people with SHORT syndrome are small at birth and gain weight slowly in childhood. Affected adults tend to have short stature compared with others in their family. Many have a lack of fatty tissue under the skin (lipoatrophy), primarily in the face, arms, and chest. This lack of fat, together with thin, wrinkled skin and veins visible beneath the skin, makes affected individuals look older than their biological age. This appearance of premature aging is sometimes described as progeroid.

Most people with SHORT syndrome have distinctive facial features. These include a triangular face shape with a prominent forehead and deep-set eyes (ocular depression), thin nostrils, a downturned mouth, and a small chin. Eye abnormalities are common in affected individuals, particularly Rieger anomaly, which affects structures at the front of the eye. Rieger anomaly can be associated with increased pressure in the eye (glaucoma) and vision loss. Some people with SHORT syndrome also have dental abnormalities such as delayed appearance (eruption) of teeth in early childhood, small teeth, fewer teeth than normal (hypodontia), and a lack of protective covering (enamel) on the surface of the teeth.

Other signs and symptoms that have been reported in people with SHORT syndrome include immune system abnormalities, a kidney disorder known as nephrocalcinosis, hearing loss, loose (hyperextensible) joints, and a soft out-pouching in the lower abdomen called an inguinal hernia. A few affected individuals have developed problems with blood sugar regulation including insulin resistance and diabetes. Most people with SHORT syndrome have normal intelligence, although a few have been reported with mild cognitive impairment or delayed development of speech in childhood.

How common is SHORT syndrome?

SHORT syndrome is a rare condition; its prevalence is unknown. Only a few affected individuals and families have been reported worldwide.

What genes are related to SHORT syndrome?

SHORT syndrome results from mutations in the PIK3R1 gene. This gene provides instructions for making one part (subunit) of an enzyme called PI3K, which plays a role in chemical signaling within cells. PI3K signaling is important for many cell activities, including cell growth and division, movement (migration) of cells, production of new proteins, transport of materials within cells, and cell survival. Studies suggest that PI3K signaling may be involved in the regulation of several hormones, including insulin, which helps control blood sugar levels. PI3K signaling may also play a role in the maturation of fat cells (adipocytes).

Mutations in the PIK3R1 gene alter the structure of the subunit, which reduces the ability of PI3K to participate in cell signaling. Researchers are working to determine how these changes lead to the specific features of SHORT syndrome. PI3K's role in insulin activity may be related to the development of insulin resistance and diabetes, and problems with adipocyte maturation might contribute to lipoatrophy in affected individuals. It is unclear how reduced PI3K signaling is associated with the other features of the condition.

Related Gene(s)

Changes in this gene are associated with short stature, hyperextensibility, hernia, ocular depression, Rieger anomaly, and teething delay.

  • PIK3R1

How do people inherit SHORT syndrome?

SHORT syndrome has an autosomal dominant pattern of inheritance, which means one copy of the altered PIK3R1 gene in each cell is sufficient to cause the disorder. In most cases, the condition results from a new mutation in the gene and occurs in people with no history of the disorder in their family. In other cases, an affected person inherits the mutation from one affected parent.

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

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

  • Gene Review: SHORT Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK201365)
  • Genetic Testing Registry: SHORT syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0878684)

You might also find information on the diagnosis or management of SHORT syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/short-stature-hyperextensibility-hernia-ocular-depression-rieger-anomaly-and-teething-delay/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/short-stature-hyperextensibility-hernia-ocular-depression-rieger-anomaly-and-teething-delay/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 SHORT syndrome?

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

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

What other names do people use for SHORT syndrome?

  • growth retardation-Rieger anomaly
  • lipodystrophy, partial, with Rieger anomaly and short stature
  • short stature-hyperextensibility-Rieger anomaly-teething delay

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 SHORT syndrome?

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

What glossary definitions help with understanding SHORT syndrome?

adipocytes ; autosomal ; autosomal dominant ; cell ; depression ; diabetes ; enamel ; enzyme ; fat cells ; fatty tissue ; gene ; glaucoma ; hernia ; hypodontia ; immune system ; inguinal ; inheritance ; insulin ; insulin resistance ; kidney ; lipodystrophy ; mutation ; new mutation ; pattern of inheritance ; prevalence ; short stature ; stature ; subunit ; syndrome ; tissue ; veins

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

References

  • Chudasama KK, Winnay J, Johansson S, Claudi T, König R, Haldorsen I, Johansson B, Woo JR, Aarskog D, Sagen JV, Kahn CR, Molven A, Njølstad PR. SHORT syndrome with partial lipodystrophy due to impaired phosphatidylinositol 3 kinase signaling. Am J Hum Genet. 2013 Jul 11;93(1):150-7. doi: 10.1016/j.ajhg.2013.05.023. Epub 2013 Jun 27. (http://www.ncbi.nlm.nih.gov/pubmed/23810379?dopt=Abstract)
  • Dyment DA, Smith AC, Alcantara D, Schwartzentruber JA, Basel-Vanagaite L, Curry CJ, Temple IK, Reardon W, Mansour S, Haq MR, Gilbert R, Lehmann OJ, Vanstone MR, Beaulieu CL; FORGE Canada Consortium, Majewski J, Bulman DE, O'Driscoll M, Boycott KM, Innes AM. Mutations in PIK3R1 cause SHORT syndrome. Am J Hum Genet. 2013 Jul 11;93(1):158-66. doi: 10.1016/j.ajhg.2013.06.005. Epub 2013 Jun 27. (http://www.ncbi.nlm.nih.gov/pubmed/23810382?dopt=Abstract)
  • Koenig R, Brendel L, Fuchs S. SHORT syndrome. Clin Dysmorphol. 2003 Jan;12(1):45-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12514365?dopt=Abstract)
  • Schroeder C, Riess A, Bonin M, Bauer P, Riess O, Döbler-Neumann M, Wieser S, Moog U, Tzschach A. PIK3R1 mutations in SHORT syndrome. Clin Genet. 2014 Sep;86(3):292-4. doi: 10.1111/cge.12263. Epub 2013 Oct 17. (http://www.ncbi.nlm.nih.gov/pubmed/23980586?dopt=Abstract)
  • Thauvin-Robinet C, Auclair M, Duplomb L, Caron-Debarle M, Avila M, St-Onge J, Le Merrer M, Le Luyer B, Héron D, Mathieu-Dramard M, Bitoun P, Petit JM, Odent S, Amiel J, Picot D, Carmignac V, Thevenon J, Callier P, Laville M, Reznik Y, Fagour C, Nunes ML, Capeau J, Lascols O, Huet F, Faivre L, Vigouroux C, Rivière JB. PIK3R1 mutations cause syndromic insulin resistance with lipoatrophy. Am J Hum Genet. 2013 Jul 11;93(1):141-9. doi: 10.1016/j.ajhg.2013.05.019. Epub 2013 Jun 27. (http://www.ncbi.nlm.nih.gov/pubmed/23810378?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: December 2013
Published: October 20, 2014