Since its initial description more than 50 years ago, SHORT syndrome is an acronym composed of the five main clinical characteristics encountered in the few patients reported in the medical literature so far [1] [2] [3] [4]:

• Short stature - Although up to one-third of cases present in the lower range of normal body height, short stature and a small height relative to the gestational age is a defining feature of this syndrome [5]. In addition to intrauterine growth retardation (IGR), which is readily noted, microcephaly, delayed bone age, and gracile long bones are observed in the majority of cases [5].
• Hyperextensibility of joints and/or hernias - Present only in a minority of individuals (around 35%).
• Ocular depression and Rieger anomaly - Dysgenesis of the anterior chamber, often described in the literature as the Rieger anomaly, is a cardinal feature and is seen in 100% of SHORT syndrome patients [1] [3] [4] [6].
• Tooth eruption delay - Similarly to ocular depression, delay in the eruption of teeth is confirmed in almost every patient suffering from SHORT syndrome [3] [4] [6].

In addition to the above mentioned signs and symptoms, several other features are described in this small group of individuals: facial anomalies (micrognathia, a triangular appearance of the face, megalocornea, anteverted ears, and hypoplasia of the nasal alae), lipodystrophy (near complete absence of subcutaneous fat), insulin resistance and eventual development of diabetes mellitus, hearing impairment, clinodactyly, and normal intellectual development, which may be particularly important in distinguishing SHORT syndrome from many other genetic diseases that affect mental development [1] [6] [7].

• Short Stature

  Acronym SHORTS Synonyms Partial lipodystrophy with Rieger anomaly and short stature Short stature, hyperextensibility, hernia, ocular depression, Rieger anomaly and teething delay Keywords Any medical or genetic information present in this entry is provided [uniprot.org]

  The facial appearance and some of the features resemble the SHORT syndrome, the name being an acronym for Short stature, Hyperextensible joints, Ocular depression, Rieger anomaly and abnormalities of the Teeth. [ncbi.nlm.nih.gov]

  Approach to short stature. Indian J Pediatr 2015; 82: 462-470. Hasegawa K, Tanaka H. Children with short‐limbed short stature in pediatric endocrinological services in Japan. Pediatr Intern 2014; 56; 809-812. [alliedacademies.org]

  This syndrome is characterized by short stature, shawl scrotum, facial abnormality, and clinodactyly. [jmgims.co.in]

  Stature Doctors at Riley at IU Health use the following exams and tests to diagnose short stature: Physical exam. [rileychildrens.org]

• Anemia

  These may appear as anemia, hyperkeratosis (scaling of the skin), easy bruising, muscle spasms, poor blood clotting, and bone pain. Causes [ edit ] Short bowel syndrome in adults and children is usually caused by surgery. [en.wikipedia.org]

  These symptoms may include: Abdominal pain Bacterial infection Bloating Cramping Diarrhea Flatulence (intestinal gas) Fatigue Food sensitivities Heartburn Low blood counts (anemia) Oily or foul-smelling stool (steatorrhea) Thin or fragile bones (osteoporosis [stanfordhealthcare.org]

  Treatment of vitamin deficiency and anemia is also very important. It is hoped that the bowel will grow in size and adapt to eventually be able to perform all the required functions without the need for IV nutrition. [cincinnatichildrens.org]

  If your child's growth disorder or short stature is caused by an underlying medical condition, treatment of that condition may improve growth: Anemia. Untreated anemia can stunt a child's growth. [rileychildrens.org]

  Problems associated with dehydration and malnutrition include weight loss, weakness, fatigue, anemia, and bacterial infections. [medicinenet.com]

• Short Stature in Children

  Short Stature in Children Related Articles Short Stature in Children Overview The term short stature describes height that is significantly below the average height for a person's age, sex, racial group, or family. [emedicinehealth.com]

  Growth disorders and short stature can mean that your child is significantly shorter than other children of his or her gender and age. [rileychildrens.org]

  What is Idiopathic Short Stature? Idiopathic Short Stature (also known as ISS) is a big name for children who are short with no known cause. ISS is a problem that can be present in both boys and girls. [magicfoundation.org]

  Idiopathic, where there is no identifiable cause of short stature. Most children with short stature will have constitutional delay of growth and puberty (CDGP) or familial short stature, or there will be no identifiable cause. [patient.info]

  Common characteristics include distinctive facial features, short stature and skeletal abnormalities, and mild to moderate intellectual disability. [rch.org.au]

• Delayed Speech Development

  We describe a boy with the manifestations of the SHORT syndrome: lipoatrophy, delayed speech development, minor facial anomalies, clinodactyly, and short stature. [ncbi.nlm.nih.gov]

  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 [rarediseases.info.nih.gov]

• Failure to Thrive

  Feeding difficulties and/or failure to thrive present in early childhood and final adult height is shorter than average (155-163 cm in males and 143-160 cm in females). [orpha.net]

  Child does not gain weight (sometimes labeled “failure to thrive”) Dehydration Vitamin deficiencies as a result of poor absorption in the intestine Ulcers from excess stomach acid Bacterial overgrowth in areas of dilated intestine Kidney stones or gallstones [cincinnatichildrens.org]

  […] to thrive Hyperphagia does not occur until the approximate age of three years and is associated with polydipsia. [patient.info]

  Growth disorders include: Failure to thrive, which isn't a specific growth disorder itself, but can be a sign of an underlying condition causing growth problems. [m.kidshealth.org]

• Delayed Dentition

  SHORT syndrome is a rare, multisystem disease characterized by short stature, anterior-chamber eye anomalies, characteristic facial features, lipodystrophy, hernias, hyperextensibility, and delayed dentition. [ncbi.nlm.nih.gov]

  Delayed dentition, hypodontia, enamel hypoplasia, malocclusion and multiple dental caries are frequently reported. Ophthalmic anomalies (e.g. Rieger anomaly, Axenfeld anomaly (see these terms), glaucoma) are also characteristic of the disease. [orpha.net]

• Dental Caries

  Delayed dentition, hypodontia, enamel hypoplasia, malocclusion and multiple dental caries are frequently reported. Ophthalmic anomalies (e.g. Rieger anomaly, Axenfeld anomaly (see these terms), glaucoma) are also characteristic of the disease. [orpha.net]

  Thus, dental problems like overcrowded teeth (5/6), hypodontia, and dental caries in SHORT syndrome patients warrant a closer look and early identification before they progress further down the road. [bmcmedgenet.biomedcentral.com]

  Dental problems consist of delayed secondary tooth eruption, small or absent teeth, malposition, malocclusion, overcrowding of teeth, dental caries on the perilingual maxillary surface (due to gastro-oesophageal reflux disease (GERD)), periodontal disease [nature.com]

• Hearing Impairment

  impairment, clinodactyly, and normal intellectual development, which may be particularly important in distinguishing SHORT syndrome from many other genetic diseases that affect mental development. [symptoma.com]

  Affiliated tissues include eye and skin, and related phenotypes are inguinal hernia and sensorineural hearing impairment OMIM®: 57 'Short,' the mnemonic designation for this syndrome, is an acronym: S = stature; H = hyperextensibility of joints or hernia [malacards.org]

  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. [rarediseases.info.nih.gov]

• Low Set Ears

  It is characterized by short stature, webbed neck, hypertelorism, low-set ears, deafness, and thrombocytopenia or abnormal platelet function. [icd10data.com]

  […] of the eye) Ptosis (drooping of the eyelids) Proptosis (bulging eyes) Refractive visual errors Strabismus (inward or outward turning of the eyes) Nystagmus (jerking movement of the eyes) Nose [ edit ] Small, upturned nose Ears and hearing [ edit ] Low-set [en.wikipedia.org]

  If your child has Kabuki syndrome, they may have: wide eyes with arched, interrupted eyebrows (a gap in the eyebrows) large and low-set ears a flat nasal tip (or squashed-looking nose) short stature (most children with Kabuki syndrome are below the 50th [rch.org.au]

  Eyes eyes that slant downwards droopy eyelids (ptosis) a squint (strabismus) lazy eye (amblyopia) cataracts – cloudy patches in the lens at the front of the eye short-sightedness (myopia) Ears low-set ears recurring middle ear infections (otitis media [nhs.uk]

  Some common physical signs of the disorder include a small head, flattened face, short neck, up-slanted eyes, low-set ears, enlarged tongue and lips, and sloping underchin. [britannica.com]

• Visual Impairment

  Such eye abnormalities may result in varying degrees of visual impairment. In cases of blepharospasm, an inability to open the eyelids due to involuntary muscle spasms may result in functional blindness. [rarediseases.org]

  The primary characteristics are: -Visual impairment caused by retinal abnormalities -Obesity, typically apparent by age one -Polydactyly (extra fingers or toes) -Hypogonadism -Renal anomalies (kidney malformations and/or malfunctions) -Learning disabilities [bardetbiedl.org]

  Children with Down syndrome are at increased risk for visual impairment. Common visual problems include crossed eyes, near- or farsightedness, and cataracts. Most visual problems can be improved with glasses, surgery, or other treatments. [stanfordchildrens.org]

  Visual and hearing impairments in addition to intellectual disability may further limit the child’s overall function and may prevent him or her from participating in important learning processes and developing appropriate language and interpersonal skills [emedicine.medscape.com]

  Visual impairments occur in 44–53% of individuals with NIPBL, SMC1A and HDAC8 variants 3, 41 and those without detectable disease-causing variants 98. [nature.com]

• Hyperextensible Joints

  The facial appearance and some of the features resemble the SHORT syndrome, the name being an acronym for Short stature, Hyperextensible joints, Ocular depression, Rieger anomaly and abnormalities of the Teeth. [ncbi.nlm.nih.gov]

  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 [medlineplus.gov]

  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 [ghr.nlm.nih.gov]

  The name is a mneumonic for the common features observed in SHORT syndrome that include; short stature, hyperextensibility of joints, ocular depression, Rieger anomaly and teething delay. [malacards.org]

  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 [rarediseases.info.nih.gov]

• Alopecia

  […] 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 [rarediseases.info.nih.gov]

• Aggressive Behavior

  […] teach kids social skills counseling with a mental health professional Doctors may prescribe medicines to help with some of the problems associated with FAS, including attention deficit hyperactivity disorder (ADHD), depression, aggressive behavior, sleep [kidshealth.org]

• Chin Dimples

  Other features characteristic of the syndrome included intrauterine growth retardation (IUGR), slow weight gain, frequent illness, triangular face, anteverted ears, telecanthus, deeply set eyes, wide nasal bridge, hypoplastic alae nasi, chin dimple, micrognathia [ncbi.nlm.nih.gov]

  […] addition to these there can be numerous associated minor features which include intrauterine growth restriction (IUGR) slow weight gain frequent illness triangular facies anteverted ears telecanthus deep-set eyes wide nasal bridge hypoplastic alae nasi chin [radiopaedia.org]

  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 [rarediseases.info.nih.gov]

• Thin Lips

  Physical examination showed a triangular-shaped face, small chin, large low-set ears, thin lip, downturned mouth, obvious beard and bushy eyebrows (Fig. 1a,b,c,d). [bmcmedgenet.biomedcentral.com]

  Some characteristic features of the face include triangular-shaped face, prominent forehead, deeply-set eyes, thin or underdeveloped nostrils (hypoplastic nasal alae), thin lips and mouth downturned, a small chin with a dimple, low-set ears, wrinkles [ijponline.biomedcentral.com]

• Dizziness

  This heartbeat pattern can cause your child to become very dizzy or faint without warning. [intermountainhealthcare.org]

  Other symptoms include heart palpitations (in almost 1 in 3 people), dizziness and fainting or syncope (in about 1 in 4 people). [my.clevelandclinic.org]

  It causes palpitations, shortness of breath, dizziness, chest tightness and fatigue. It can occur in short episodes, starting and stopping by themselves, or it can become a more permanent condition. [sads.org]

  A five to eight percent decrease can cause fatigue and dizziness. Loss of over ten percent of total body water can cause physical and mental deterioration, accompanied by severe thirst. [en.wikipedia.org]

• Tremor

  The tremor in the present family, which was a constant, fine tremor, differs from the Parkinsonian tremor seen in Waisman-Laxova syndrome (MIM 311510) and in the intention tremors described in the Pettigrew syndrome (MIM 304340) and ataxia dementia (MIM [jmg.bmj.com]

  (2 in) of midparental height, bone age greater than chronologic age, normal growth velocity after catch-up growth Growth velocity, bone age Endocrine disorders Hyperthyroidism Rapid childhood growth, goiter, tachycardia, hypertension, diarrhea, fine tremor [aafp.org]

  CN 3, 4) Weber's syndrome ventral peduncle, PCA Benedikt syndrome ventral tegmentum, PCA Parinaud's syndrome dorsal, tumor Nothnagel's syndrome Claude's syndrome Other Alternating hemiplegia Cerebellum lateral ( Dysmetria Dysdiadochokinesia Intention tremor [en.wikipedia.org]

• Average Intelligence

  While some individuals with autism have intellectual disabilities, by definition, a person with Asperger’s Disorder cannot have a “clinically significant” cognitive delay, and most possess average to above-average intelligence. [autism-society.org]

  Although these children may also possess signs of low blood sugar or obesity, they display average body proportions and (average intelligence. [hgfound.org]

• Neurologic Manifestation

  Specifically, IVIG plus corticosteroids group patients had higher frequency of respiratory, ocular, and cardiovascular involvement compared with the corticosteroids group and more neurologic manifestations compared with the IVIG group. [jamanetwork.com]

  MRI findings usually do not contribute to regular clinical care and should be limited to individuals with CdLS with neurological manifestations (R48). [nature.com]

Given the rarity of the condition (only 20 cases described until the end of the 20th century), the diagnosis of SHORT syndrome is difficult. But because clinical suspicion can only be raised after a thorough physical examination and a properly obtained patient history, these two steps must be regarded as essential in order to make the diagnosis. Identification of the five cardinal features that constitute the SHORT acronym will almost undoubtedly confirm the diagnosis. On the other hand, several reports imply that an autosomal dominant pattern of inheritance is the mode of SHORT syndrome transmission, although many cases have developed following de novo mutations without any association suggesting a familial event [1] [2] [6]. Nevertheless, a comprehensive family history should be obtained. The cause of SHORT syndrome was unknown until recently, but the discovery of phosphatidylinositol 3 kinase (PI3K) mutations in practically all individuals has opened up the possibility of genetic testing in patients with the typical clinical features of SHORT [1] [3] [5]. These tests are scarcely available, however, which is why the diagnosis rests on clinical criteria. Mutations in BMP4 and the PITX family of genes have also been described in certain studies, but their roles are yet to be confirmed [5] [6].

• Delayed Bone Age

  Additionally, the patients usually present a low birth weight and height, lipodystrophy, delayed bone age, hernias, low body mass index and a progeroid appearance. [ncbi.nlm.nih.gov]

  bone age delayed speech glucose intolerance insulinopenic diabetes Affected individuals are thought to have normal intellect or mild intellectual disability. [radiopaedia.org]

  In addition to intrauterine growth retardation (IGR), which is readily noted, microcephaly, delayed bone age, and gracile long bones are observed in the majority of cases. [symptoma.com]

  delayed bone age, hernias and progeroid appearance, that has material basis in heterozygous mutation in PIK3R1 on chromosome 5q13. [malacards.org]

• Pericardial Effusion

  Cardiovascular features were less prominent in the corticosteroids group, which had higher median initial left ventricular ejection fraction (LVEF), lower frequency of pericardial effusion, and less vasoactive use compared with the IVIG and IVIG plus [jamanetwork.com]

• Short QT Interval

  […] a short QT interval, and, therefore, be under suspicion of having Short QT Syndrome. [shortqtsyndrome.org]

  Jose Luis Merino, FESC Short QT syndrome is an inherited cardiac channelopathy characterised by an abnormally short QT interval and an increased risk of atrial and ventricular arrhythmias. [escardio.org]

  Abstract Short QT syndrome (SQTS) is an inherited cardiac channelopathy characterised by an abnormally short QT interval and increased risk for atrial and ventricular arrhythmias. [aerjournal.com]

  […] of short QT intervals in healthy individuals. [circep.ahajournals.org]

Management and treatment Treatment is symptomatic and requires a multidisciplinary team. Screening for insulin resistance is recommended starting in mid-late childhood. [orpha.net]

Most cases of SBS are unique, so treatments often must be tailored to each case. Infants are at a critical stage in life and sensitive to treatments. Some SBS treatments that work for children and adults can’t be used on infants. [eurostemcell.org]

The main treatment for short bowel syndrome is nutritional support. Treatment may involve use of oral rehydration solutions, parenteral nutrition, enteral nutrition, and medications. [iffgd.org]

Treatment Treatment has two goals: to ease symptoms and give you enough vitamins and minerals. The kind of treatment you get depends on how severe your condition is. [webmd.com]

[…] beginning treatment with teduglutide. [clinicaltrials.gov]

Aim To characterize a Portuguese population with TTS and to determine their short- and medium-term prognosis. [revportcardiol.org]

Prognosis Individuals with SHORT syndrome are considered to have a normal life-expectancy. The documents contained in this web site are presented for information purposes only. [orpha.net]

Prognosis: The condition is lethal due to severe pulmonary hypoplasia. Recurrence: Autosomal recessive inheritance: 25%. [fetalmedicine.org]

Objectives Definition Etiology Clinical manifestation Management prognosis Complication 3. Definition It is a malabsorpative state that may follow massive resection of small intestine. [slideshare.net]

Prognosis [ edit ] There is no cure for short bowel syndrome except transplant. In newborn infants, the 4-year survival rate on parenteral nutrition is approximately 70%. [en.wikipedia.org]

As part of the FORGE (Finding of Rare Disease Genes) Canada Consortium, we studied individuals with clinical features of SHORT syndrome to identify the genetic etiology of this rare disease. [ncbi.nlm.nih.gov]

Etiology SHORT syndrome is due to mutations in the PIK3R1 gene (5q13.1), encoding phosphatidylinositol 3-kinase regulatory subunit alpha. [orpha.net]

Sixteen (57.1%) patients had an underlying etiology of necrotizing enterocolitis (NEC). [journals.lww.com]

Short bowel syndrome is a malabsorptive condition characterized by extreme reduction in functional small intestinal length most commonly as a result of surgical resection due to mesenteric ischemia or Inflammatory Bowel Disease (IBD) although other etiologies [mayo.edu]

Summary Epidemiology The prevalence of SHORT syndrome is unknown. Less than 50 cases have been reported in the literature to date. Clinical description Individuals with SHORT syndrome often display mild intrauterine growth restriction. [orpha.net]

Epidemiology Epidemiology is highly variable as this condition often reflects injury sequelae and not the distribution of a genetic disease. [cancertherapyadvisor.com]

The Centre for Epidemiology. The Swedish Hospital Discharge Register. Stockholm: The National Board of Health and Welfare, 1999. Available from: http://www.sos.se/epc/english/ParEng.htm 21. The Centre for Epidemiology. [revespcardiol.org]

This study defines a clinically recognizable incomplete dominant form of SHORT syndrome, and provides relevant insights into the pathophysiological and phenotypical consequences of IGF1R mutations. [ncbi.nlm.nih.gov]

Outline • Anatomy • Physiology • Definition • Pathophysiology • Classification(including etiology) • Clinical Presentation • Workup • Treatment 3. [slideshare.net]

A complete understanding of the pathophysiology of SBS and postoperative adaptations may allow identifying the spontaneous processes that compensate for the reduction in absorptive surface. [nutricionhospitalaria.org]

Pathophysiology The general pathophysiology is one of an absolute or functional lack of appropriate small intestine to manage nutrient processing and absorption as well as water absorption. [cancertherapyadvisor.com]

Pathophysiology Maintenance of normal bodily functions and homeostasis is dependent on sufficient intestinal absorption of essential macronutrients, micronutrients, and fluids. [mdedge.com]

(PEP), HIV medicine taken within 72 hours after a possible exposure to prevent the virus from taking hold. [hiv.gov]

Try to prevent your child from getting startled or scared, or avoid situations that may cause them to get too excited or angry. [intermountainhealthcare.org]

[…] appropriate discharges Prevention of symptomatic episodes of atrial fibrillation However, drugs must be used with caution since the long-term efficacy of drug therapy in preventing serious arrhythmic events has been studied only in SQTS 1 patients and [escardio.org]

For the average person, eating a diet high in fiber from whole foods is important for staying healthy and preventing disease. [columbiasurgery.org]

1. Dyment DA, Smith AC, Alcantara D, et al. Mutations in PIK3R1 Cause SHORT Syndrome. Am J Hum Genet. 2013;93(1):158-166.
2. Lipson AH, Cowell C, Gorlin RJ. The SHORT syndrome: further delineation and natural history. Journal of Medical Genetics. 1989;26(7):473-475.
3. Chudasama KK, Winnay J, Johansson S, et al. SHORT Syndrome with Partial Lipodystrophy Due to Impaired Phosphatidylinositol 3 Kinase Signaling. Am J Hum Genet. 2013;93(1):150-157.
4. Koenig R, Brendel L, Fuchs S. SHORT syndrome. Clin Dysmorphol. 2003;12(1):45-49.
5. Thauvin-Robinet C, Auclair M, Duplomb L, et al. PIK3R1 Mutations Cause Syndromic Insulin Resistance with Lipoatrophy. Am J Hum Genet. 2013;93(1):141-149.
6. Singh A, Arora R, Singh P, Kapoor S. Short syndrome-an expanding phenotype. Indian Pediatr. 2013;50(4):414-416.
7. Joo SH, Raygada M, Gibney S, Farzaneh I, Rennert OM. Case report on SHORT syndrome. Clin Dysmorphol. 1999;8(3):219-221.