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Disease Profile

SHORT syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Neonatal

ICD-10

Q87.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Short stature, Hyperextensibility, Hernia, Ocular depression, Rieger anomaly and Teething delay; Aarskog-Ose-Pande syndrome; Partial lipodystrophy with Rieger anomaly and short stature

Categories

Congenital and Genetic Diseases; Endocrine Diseases; Eye diseases;

Summary

SHORT syndrome is a condition characterized by multiple abnormalities that affect several parts of the body. The term SHORT is an acronym with each letter representing a common feature in affected individuals: (S) short stature; (H) hyperextensibility of joints and/or hernia (inguinal); (O) ocular depression (deep-set eyes); (R) Rieger anomaly (defective development of the anterior chamber of the eye that can lead to glaucoma); and (T) teething delay. Other features commonly present include a triangular face, small chin with a dimple, loss of fat under the skin (lipodystrophy), abnormal position of the ears, hearing loss and delayed speech.[1] It is caused by mutations in the PIK3R1 gene. Inheritance is autosomal dominant. Treatment focuses on the specific symptoms present in each individual.[2]

Symptoms

SHORT syndrome is a disorder that affects multiple parts of the body. It is mainly characterized by several features that are represented by the acronym SHORT: (S) short stature; (H) hyperextensible joints (joints that stretch more than usual) and/or hernia (inguinal); (O) ocular depression (deep-set eyes); (R) Rieger anomaly (defective development of the anterior chamber of the eye that can lead to glaucoma); and (T) teething delay.[1] A loss of fat under the skin (lipodystrophy), usually most prominent in the face and upper body, is also a main feature of the syndrome.[1][3]

Affected individuals often have additional, distinctive, facial features including a small chin with a dimple; triangular-shaped face; prominent forehead; abnormal positioning of the ears; large ears; underdeveloped (hypoplastic) or thin nostrils; and thin, wrinkled skin that gives the impression of premature aging.[1][3]

Intelligence is often normal, but some affected individuals have speech delay and/or other developmental delays in childhood.[1][3] Hearing loss is common. Affected infants may have difficulty gaining weight and may be prone to illnesses. Individuals may also develop diabetes in the second decade of life.[1]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Deeply set eye
Deep set eye
Deep-set eyes
Sunken eye

[ more ]

0000490
Hypoplasia of the iris
Underdeveloped iris
0007676
Inguinal hernia
0000023
Joint hyperflexibility
Joints move beyond expected range of motion
0005692
Sensorineural hearing impairment
0000407
Severe short stature
Dwarfism
Proportionate dwarfism
Short stature, severe

[ more ]

0003510
30%-79% of people have these symptoms
Abnormal pupil morphology
Abnormality of the pupil
Pupillary abnormalities
Pupillary abnormality

[ more ]

0000615
Abnormality of dental enamel
Abnormal tooth enamel
Enamel abnormalities
Enamel abnormality

[ more ]

0000682
Alopecia
Hair loss
0001596
Diabetes mellitus
0000819
Excessive wrinkled skin
0007392
Glaucoma
0000501
Insulin resistance
Body fails to respond to insulin
0000855
Lipodystrophy
Inability to make and keep healthy fat tissue
0009125
Megalocornea
Enlarged cornea
0000485
Microdontia
Decreased width of tooth
0000691
Midface retrusion
Decreased size of midface
Midface deficiency
Underdevelopment of midface

[ more ]

0011800
Neurological speech impairment
Speech disorder
Speech impairment
Speech impediment

[ more ]

0002167
Poor appetite
Decreased appetite
0004396
Sparse hair
0008070
Weight loss
0001824
5%-29% of people have these symptoms
Abnormal anterior chamber morphology
0000593
Abnormality of the mandible
Abnormality of the lower jaw bone
0000277
Brachydactyly
Short fingers or toes
0001156
Corneal opacity
0007957
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Malar flattening
Zygomatic flattening
0000272
Posterior embryotoxon
0000627
Prominent forehead
Pronounced forehead
Protruding forehead

[ more ]

0011220
Prominent supraorbital ridges
Prominent brow
0000336
Short palm
0004279
Telecanthus
Corners of eye widely separated
0000506
Triangular face
Face with broad temples and narrow chin
Triangular facial shape

[ more ]

0000325
Wide nasal bridge
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge

[ more ]

0000431
Percent of people who have these symptoms is not available through HPO
Abnormality of the immune system
Immunological abnormality
0002715
Abnormality of the skin
0000951
Autosomal dominant inheritance
0000006
Birth length less than 3rd percentile
0003561
Cataract
Clouding of the lens of the eye
Cloudy lens

[ more ]

0000518
Clinodactyly
Permanent curving of the finger
0030084
Delayed eruption of teeth
Delayed eruption
Delayed teeth eruption
Delayed tooth eruption
Eruption, delayed
Late eruption of teeth
Late tooth eruption

[ more ]

0000684
Delayed skeletal maturation
Delayed bone maturation
Delayed skeletal development

[ more ]

0002750
Delayed speech and language development
Deficiency of speech development
Delayed language development
Delayed speech
Delayed speech acquisition
Delayed speech development
Impaired speech and language development
Impaired speech development
Language delay
Language delayed
Language development deficit
Late-onset speech development
Poor language development
Speech and language delay
Speech and language difficulties
Speech delay

[ more ]

0000750
Dental malocclusion
Bad bite
Malalignment of upper and lower dental arches
Misalignment of upper and lower dental arches

[ more ]

0000689
Dimple chin
Chin butt
Chin dent
Chin dimple
Chin skin dimple
Indentation of chin

[ more ]

0010751
Downturned corners of mouth
Downturned corners of the mouth
Downturned mouth

[ more ]

0002714
Enlarged epiphyses
Large end part of bone
0010580
Frontal bossing
0002007
Hyperglycemia
High blood sugar
0003074
Hypodontia
Failure of development of between one and six teeth
0000668
Insulin-resistant diabetes mellitus
Insulin resistant diabetes
Insulin-resistant diabetes

[ more ]

0000831

Diagnosis

There is no formal criteria for diagnosis yet. The term “SHORT syndrome” was first created to reflect several of the features of the original reported cases: Short stature, Hyperextensibility, Ocular depression (deeply set eyes), Rieger anomaly, and Teething delay. However, it is now recognized that all of these five features are neither required to make the diagnosis nor necessarily the most specific features of SHORT syndrome.[2]

The features most consistently observed in SHORT syndrome include:[2]

  • Intrauterine growth restriction (IUGR)
  • Short stature
  • Partial lipodystrophy
  • Facial characteristics: Face with triangular shape, prominent forehead, deep-set eyes, nose with a narrow low-hanging tip and thin nasal alae, small chin with a central dimple and large ears that are low-set.

Other frequent features include:[3][2]

  • Axenfeld-Rieger anomaly or related eye anomalies
  • Delayed dentition
  • Diabetes.

In general, the facial features allow to make a suspicion of the diagnosis. Diagnosis is confirmed with the genetic testing showing a mutation in the PIK3R1 gene.

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Organizations Providing General Support

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • Genetics Home Reference (GHR) contains information on SHORT syndrome. This website is maintained by the National Library of Medicine.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        In-Depth Information

        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss SHORT syndrome. Click on the link to view a sample search on this topic.

          References

          1. SHORT syndrome. NORD. August 17, 2007; https://www.rarediseases.org/rare-disease-information/rare-diseases/byID/938/viewAbstract.
          2. Innes AM. SHORT Syndrome. GeneReviews. May 15, 2014; https://www.ncbi.nlm.nih.gov/books/NBK201365/.
          3. Koenig, Rainer; Brendel, Leticia; Fuchs, Sigrun. SHORT syndrome. Clinical Dysmorphology. January 2003; 12(1):45-49.

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