NORD gratefully acknowledges Emily Fishman, NORD Editorial Intern, and A. Micheil Innes, MD, FRCPC, FCCMG, Department of Medical Genetics, University of Calgary, Alberta Children’s Hospital Research Institute for Child and Maternal Health, Calgary, Alberta, Canada, for assistance in the preparation of this report.
SHORT syndrome is a rare condition in which affected individuals have multiple birth defects in different organ systems. SHORT syndrome was first described by RJ Gorlin et al in 1975 based on the striking physical features of two infants born to normal parents. Over time, more affected individuals have been described and the clinical definition of SHORT syndrome has been expanded. Each letter of SHORT syndrome represents one of the common findings in affected persons:
(S) = short stature
(H) = hyperextensibility of joints and/or hernia (inguinal)
(O) = ocular depression (deep-set eyes)
(R) = Rieger anomaly (defective development of the eye that often leads to glaucoma)(T) = teething delay
Not all of these five features are required for diagnosis of SHORT syndrome.
Other characteristics common in SHORT syndrome are a triangular face, small chin with a dimple, a loss of fat under the skin (lipodystrophy), abnormal position of the ears, hearing loss, intrauterine growth restriction (IUGR) (poor fetal growth and low weight), and delayed speech.
SHORT syndrome is a disorder that affects multiple organ systems. This condition was initially characterized by short stature, joints that stretch more than usual (hyperextensibility), a particular type of hernia in which the intestine protrudes through a weak spot in the abdominal muscles (inguinal hernia), deep set eyes (ocular depression), defective development of the anterior chamber of the eye that can lead to glaucoma (Rieger anomaly) and delayed eruption of teeth.
In addition to the classic features, other characteristics that are common in SHORT syndrome include a triangular face, small chin with a dimple, abnormal position of the ears, and hearing loss. Loss of fat under the skin (lipodystrophy) is also common, causing difficulty gaining weight and a translucent appearance to the skin. This typically presents first in the face followed by the chest and upper extremities in the first few years of development. Often, the lower extremities are spared from lipodystrophy, but overall body appearance is thin with low body mass index (BMI). Some affected individuals have speech delay and other developmental delays but intelligence is usually normal. In addition to teething delay, development of further dental issues is likely. Insulin resistance is common in mid-childhood to adolescence, often progressing into diabetes mellitus by early adulthood. Babies with SHORT syndrome are usually born at or slightly before term, but often have low birth weight, small head circumference, and shortened length. Individuals with SHORT syndrome are thought to have a normal life-expectancy.
SHORT syndrome is caused by changes (mutations) in the PIK3R1 gene. This gene is responsible for proper production of the enzyme PI3K. Enzymes are proteins that speed up the progress of cellular reactions. Specifically, PI3K is involved in many cell activities including cell growth and division, transport of materials within cells, movement of cells, and regulation of the hormone insulin.
SHORT syndrome is inherited in an autosomal dominant manner. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent if affected or can be the result of a new (de novo) mutation in the affected individual. The risk of passing the abnormal gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.
SHORT syndrome is a very rare disorder with fewer than 50 reported cases in the literature to date. SHORT syndrome is not known to be more prevalent in a certain ethnic group or geographic location.
The diagnosis of SHORT syndrome is based on physical findings and molecular genetic testing for mutations in the PIK3R1 gene.
No specific treatment exists for SHORT syndrome; however, some features can be treated separately on a case-by-case basis. Rieger anomaly/glaucoma, dental anomalies, insulin resistance/diabetes mellitus, and hearing loss can often be treated by appropriate medical specialists if present. Treatment is symptomatic and supportive. Given the increased risk for insulin resistance, it is generally advisable to avoid growth hormone treatments.
Genetic counseling is recommended for patients and their families.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov . All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.
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