NORD gratefully acknowledges Hannah Sur, Editorial Intern from the Keck Graduate Institute and Julia Thom Oxford, PhD, Distinguished Professor, Department of Biological Sciences, Biomolecular Research Center, Boise State University, for assistance in the preparation of this report.
Stuve Wiedemann syndrome (STWS) is rare genetic and disorder that has been diagnosed in very few patients. It is characterized by short stature, bowing of the long bones of the arms and legs (campomelia), and fingers or toes that are permanently flexed (camptodactyly) outward away from the thumb (ulnar deviation). Affected infants often are unable to survive past one year due to life-threatening complications such as episodes where there is a sudden rise in body temperature (hyperthermia) or respiratory distress. Those who do survive will develop severe spinal deformities, spontaneous bone fractures, temperature instability (from dysautonomia), and some general developmental delays, though no intellectual deficits have been found. STWS is inherited as an autosomal recessive trait.
In the past, STWS was thought to be a lethal condition in all affected individuals. Today, survival past the first year of life is more common if children are diagnosed early enough and are monitored properly.
The symptoms of STWS vary from person to person. Most infants develop characteristic skeletal abnormalities including fingers or toes that are permanently flexed (camptodactyly) outward away from the thumb (ulnar deviation) and bowing of the long bones of the arms and legs (camptomelia), which results in short stature. Affected infants may also have underdeveloped muscle tone (hypotonia) and/or an elbow that is permanently fixed in a bent or flexed position (elbow contracture). Some children with STWS have had distinctive facial features, including small chins (micrognathia), pursed mouth, and underdeveloped upper jaw, cheekbones, and eye sockets (midface hypoplasia) that sometimes results in protruding eyes.
Some infants with STWS may develop episodes where they repeatedly stop breathing during sleep (sleep apnea). Feeding and swallowing difficulties may also occur. In some children, life-threatening complications may develop early during infancy including respiratory distress and repeated episodes where there is a sudden rise in body temperature (hyperthermia).
Other symptoms include decreased bone density (osteopenia) and autonomic nervous system disorders (dysautonomia) that includes difficulty regulating temperature, smooth tongue, and absent corneal and patellar reflexes. Affected children will also have general developmental delays, though there have been no reports of any intellectual deficits.
The specific clinical picture of STWS is unclear because of the small number of cases reported in the medical literature. Some affected individuals develop symptoms similar to those associated with dysautonomia. (For more information on dysautonomia, see the Related Disorders section below). These symptoms may include diminished sensitivity to pain, absence of the knob-like projections that cover the tongue (fungiform papillae), excessive sweating at low temperatures, absent corneal reflexes, multiple fractures, and spinal abnormalities.
Additional findings have been reported in some children with STWS including high blood pressure of the main artery of the lungs (pulmonary hypertension), liver (hepatic) failure, and a form of clubfoot in which the heel is turned outward away from the midline of the leg (talipes valgus). It is not known whether these are characteristic findings of STWS or coincidental findings. As STWS becomes better recognized, more cases will be identified allowing for a clearer clinical picture to emerge.
STWS is inherited as an autosomal recessive trait due to a change (mutation) in the leukemia inhibitory factor receptor (LIFR) gene This mutation leads to changes in the stability of the LIFR protein transcription, which causes less of the LIFR protein to be produced, ultimately affecting the JAK/STAT3 signaling pathway. This JAK/STAT3 pathway is one of the many signaling pathways involved in human development, including different cytokines and growth factors. However, not all reported individuals have a LIFR mutation, indicating that not all of the SWS-causing genes have been identified.
Most genetic diseases are determined by the status of the two copies of a gene, one received from the father and one from the mother. Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual inherits one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the altered gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females.
Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
STWS has a very low prevalence of <1 out of 1,000,000. However, the disease is relatively common in the United Arab Emirates with a prevalence of 1 out of 20,000 births, owing to the fact that parents are often closely related by blood (consanguineous). STWS affects males and females in equal numbers. Patients with STWS often go unrecognized making it difficult to determine the true frequency of the disorder in the general population. STWS was first described in the medical literature in 1971.
STWS is usually diagnosed based on clinical and radiological findings after birth. A detailed patient history is taken into account. Radiological images show the telltale congenital contractures, bowed long bones, decreased bone density, and other abnormal patterns. Genetic testing for mutations in the LIFR gene can confirm a STWS diagnosis. At least one child with STWS was diagnosed before birth (antenatally) by fetal ultrasound during the late second or third trimester. In fetal ultrasound, sound waves are used to create an image of the developing fetus.
The treatment of STWS currently involves treatment of the symptoms of each patient. This might include prevention of choking while eating via a tube that connects the nose to the stomach for feeding (nasogastric tube), prevention of inhaling food on accident (lung aspiration), or physiotherapy and/or surgery to correct bone malformations. However, it should be noted that due to the tendency of affected individuals to have episodes of hyperthermia, use of anesthesia for procedures should be treated with extreme caution. Other treatment to consider would be for eye protection to prevent vision loss.
Genetic counseling is recommended for affected individuals and their families. Other treatment is symptomatic and supportive.
Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/ All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
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Some current clinical trials also are posted on the following page on the NORD website:
For information about clinical trials sponsored by private sources, contact:
For information about clinical trials conducted in Europe, contact:
Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder.
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Occipital Horn Syndrome. Orphanet. Last update: May 2011. http://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=7035&Disease_Disease_Search_diseaseGroup=Ehlers-Danlos-syndrome-type-IX&Disease_Disease_Search_diseaseType=Pat&Disease(s)/group%20of%20diseases=Occipital-horn-syndrome&title=Occipital-horn-syndrome&search=Disease_Search_Simple. Accessed Feb. 1, 2018.
Autosomal Dominant Larsen Syndrome. Orphanet. Last update: July 2013. http://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=3716&Disease_Disease_Search_diseaseGroup=larsen-syndrome&Disease_Disease_Search_diseaseType=Pat&Disease(s)/group%20of%20diseases=Autosomal-dominant-Larsen-syndrome&title=Autosomal-dominant-Larsen-syndrome&search=Disease_Search_Simple. Accessed Feb. 1, 2018.
Rawlings JS, Rosler KM, Harrison DA. The JAK/STAT signaling pathway. Journal of Cell Science 2004;117:1281-1283; doi: 10.1242/jcs.00963 http://jcs.biologists.org/content/117/8/1281 Accessed Feb. 1, 2018.
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