NORD gratefully acknowledges Maarit Peippo, MD, Consultant in Medical Genetics, University of Helsinki, Finland, for assistance in the preparation of this report.
Weismann-Netter-Stuhl syndrome is an extremely rare genetic skeletal disorder characterized by the abnormal development of bone (osseousbo dysplasia). Affected individuals exhibit bowing of the long portions (shafts) of the shinbone (tibia) and the outer, smaller bone of the leg below the knee (fibula). In some individuals, other bones may also be affected, such as the ribs, pelvis, spinal column, and/or bones in the arms. Affected individuals will have some degree of short stature, which means that they are shorter than would otherwise be expected based on their gender and age. The medical definition states that short stature is two standard deviations or more below the mean for children of the same age and gender. The final height of affected individuals will vary. Researchers believe that alterations (mutations) in a gene result in Weismann-Netter-Stuhl syndrome. However, they have not been able to find such a gene. Researchers also believe that the disorder is inherited in an autosomal dominant manner.
Although researchers have been able to establish a clear syndrome with characteristic or “core” symptoms, much about the disorder is not fully understood. Several factors including the small number of people identified with this disorder, the lack of large clinical studies, and the underlying cause of the disorder being unknown prevent physicians from developing a complete picture of associated symptoms and prognosis. Therefore, it is important to note that affected individuals may not have all the symptoms discussed below. Parents should talk to their children’s physicians and medical team about their specific case, associated symptoms and overall prognosis.
The major physical characteristics of Weismann-Netter-Stuhl syndrome include short stature and bowing of the front (anterior) of the long portions (shafts) of the shinbone (tibia) and the smaller bone of the leg below the knee (fibula). Sometimes the long bone of the thigh (femur) is bowed. Many affected individuals do not have any major functional limitations, and a diagnosis of Weismann-Netter-Stuhl syndrome may not be made until adolescence or adulthood because of the lack of serious complications associated with this disorder. Usually both legs are affected (bilateral). In extremely rare instances, only one leg is affected (unilateral).
Along with the characteristic bowing of the tibia and fibula, affected individuals may also exhibit bowing of the sides (lateral bowing) of the thigh bones (femur) and/or outward curvature of the tibia (saber shins). Benign (non-cancerous) overgrowths of cartilage called exostoses may affect the tibias. Additional bones may also be affected including the ribs and pelvis.
Affected individuals may also exhibit bowing of certain bones in the forearms (i.e., ulna and radius), malformation of a part of the hip bone (ilium), improper development of bone toward the bottom of the spinal column (horizontal sacrum), widening of the marrow cavities inside bones, and/or thickening of the outer layers (cortexes) of the long bones (diaphyseal dysplasia). Sometimes, a hip deformity in which the thigh bone is angled toward the center of body (coxa vara) is present.
In addition, some affected individuals may exhibit a sideways curvature of the spine (scoliosis), an inward curvature of the back (lordosis) so that the back curves into the body, and/or a front-to-back curvature of the spine (kyphosis) so that the upper back is rounded. Most affected individuals begin to walk later than is normally expected, however, the reason for this delay is not understood.
There have been reports of intellectual disability in some children as well as an enlarged thyroid (goiter) and low levels of circulating red blood cells (anemia). However, some researchers believe that these findings may be coincidental and not features of Weismann-Netter-Stuhl syndrome.
The exact, underlying cause of Weismann-Netter-Stuhl syndrome is unknown. Sometimes, the disorder runs in families. Researchers believe it is most likely caused by a change in a gene. However, no genes have been identified to be associated with the disorder. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, or absent. Depending upon the functions of the protein, this can affect many organ systems of the body.
Although no altered genes have been identified to be associated with Weismann-Netter-Stuhl syndrome, researchers believe that the disorder is inherited in an autosomal dominant manner. 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. 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 or can be the result of a new mutation (gene change) 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.
Weismann-Netter-Stuhl syndrome is an extremely rare skeletal disorder that affects males and females in equal numbers. Approximately 70 people have been reported in the medical literature since the disorder’s original description in 1954. However, because rare disorders like Weismann-Netter-Stuhl syndrome often go unrecognized, these disorders are under-diagnosed, making it difficult to determine the true frequency in the general population.
The diagnosis of Weismann-Netter-Stuhl syndrome may be confirmed by x-ray studies of the skeleton that reveal distinctive bowing of the long bones of the legs, lateral bowing of the femur, thickened outer layers of bones, and widened marrow cavities. Other x-ray findings may include bowing of certain arm bones (i.e., ulna and radius), malformation of part of the hip bone (ilium), abnormal development of part of the spinal column (horizontal sacrum), and/or hardening of a membrane that surrounds the brain and spinal cord (dural calcification).
A diagnosis of Weismann-Netter-Stuhl syndrome is difficult and often delayed because the disorder is not well known, the exact cause has not been identified, and it can be mistaken for many other disorders.
The treatment of Weismann-Netter-Stuhl syndrome is directed toward the specific symptoms that are apparent in each individual. Genetic counseling will be of benefit for affected individuals and their families. A supportive team approach for children with Weismann-Netter-Stuhl syndrome may be helpful. Such a team approach may include physical therapy and other medical, social, or vocational services.
For many people, the skeletal abnormalities do not disturb the functions of the legs or only mildly affect function. One journal article recommended surgical intervention for Weismann-Netter-Stuhl syndrome (Gupta 2014). However, if the abnormalities of the legs are not causing any functional problems, then surgery is not necessary. Decisions concerning treatment can vary for each affected individual depending on several factors including their age, severity of the skeletal malformation and misalignment, an individual’s overall health, patient preference and other appropriate factors.
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 web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
For information about clinical trials sponsored by private sources, in the main, contact:
For more information about clinical trials conducted in Europe, contact:
Samara AM, Fernandes SR. Weismann-Netter-Stuhl syndrome. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:268.
Kozlowski K, Beighton P, eds. Weismann-Netter-Stuhl Syndrome (Toxopachyosteose Diaphysaire Tibio-peroniere). In: Gamut Index of Skeletal Dysplasias: An Aid to Radiodiagnosis. 4th ed. Springer-Verlag, New York, NY; 1984:177.
Gupta P, Mittal R, Mittal S, Shankar V. Weismann-Netter-Stuhl syndrome: report of two cases and treatment. BMJ Case Report. 2014;2014. https://www.ncbi.nlm.nih.gov/pubmed/24496066
Hayrullah A, Atabek ME, Pirgon O. Weismann-Netter-Stuhl syndrome: a family report. J Clin Res Pediatr Endocrinol. 2009;1:194-196. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005653/
Peippo M, Valanne L, Perhoma M, Toivanen L, Ignatius J. Weismann-Netter syndrome and mental retardation: a new patient and review of the literature. Am J Med Genet. 2009;149A:2593-2601. https://www.ncbi.nlm.nih.gov/pubmed/19839038
Yekeler E, Ozdemir C, Gokalp S, et al. Weismann-Netter-Stuhl syndrome in two siblings. Skeletal Radiol. 2005;34:176-179. https://www.ncbi.nlm.nih.gov/pubmed/15538562
Cheema JI, Grissom LE, Harcke HT. Radiographic characteristics of lower-extremity bowing in children. Radiographics. 2003;23:871-880. https://www.ncbi.nlm.nih.gov/pubmed/12853662
Coimbra AV, Filardi S, Fernandez SR, Marques-Neto JF, Samara AM. Weismann-Netter-Stuhl syndrome: first Brazilian case reports. Joint Bone Spine. 2000;67:539-43. https://www.ncbi.nlm.nih.gov/pubmed/11195318
Kurtoglu S, Dundar M, Kumandas S, et al. Patient with Weismann-Netter and Stuhl (toxopachyosteosis) syndrome with communicant hydrocephalus and arachnoid cyst. J Pediatr Endocrinol Metab. 2000;13:211-15. https://www.ncbi.nlm.nih.gov/pubmed/10711669
Nores JM, Monsegu SH, de Masfraud V, et al. Tibioperoneal diaphyseal toxopachyosteosis or Weismann-Netter-Stuhl syndrome: difficulties encountered in classifying this syndrome and differentiation from rickets. Clin Exp Rheumatol. 19997;15:105-09. https://www.ncbi.nlm.nih.gov/pubmed/9093784
Nores JM, Monsegu SH, de Masfraud V, et al. Identification and classification of tibioperoneal diaphyseal toxopachyosteosis (Weismann-Netter-Stuhl syndrome): based on two new cases and a review of the literature. Eur J Radiol. 1997;24:71-76. https://www.ncbi.nlm.nih.gov/pubmed/9056154
Tieder M, Manor H, Peshin J, Alon US. The Weismann-Netter, Stuhl syndrome: a rare pediatric skeletal dysplasia. Pediatr Radiol. 1995;25:37-40. https://www.ncbi.nlm.nih.gov/pubmed/7761160
Hary S, Houvenagel E, Vincent G, Reiner JC. Weismann-Netter and Stuhl toxopachyosteosis. Apropos of 30 cases. Rev Rheum Mal Osteoartic. 1992;59:65-71. https://www.ncbi.nlm.nih.gov/pubmed/1579848
Hary S, Houvenagel E, Vincent G. A case of Weismann-Netter and Stuhl toxopachyosteosis with new bone sites. Rev Rhum Mal Osteoartic. 1992;59:73-75. https://www.ncbi.nlm.nih.gov/pubmed/1579849
Robinow M, Johnson GF. The Weismann-Netter syndrome. Am J Med Genet. 1988;29:573-79. https://www.ncbi.nlm.nih.gov/pubmed/3377000
McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:112350; Last Update:10/13/2016. Available at: http://www.omim.org/entry/112350 Accessed March 21, 2017.
The information in NORD’s Rare Disease Database is for educational purposes only and is not intended to replace the advice of a physician or other qualified medical professional.
The content of the website and databases of the National Organization for Rare Disorders (NORD) is copyrighted and may not be reproduced, copied, downloaded or disseminated, in any way, for any commercial or public purpose, without prior written authorization and approval from NORD. Individuals may print one hard copy of an individual disease for personal use, provided that content is unmodified and includes NORD’s copyright.
National Organization for Rare Disorders (NORD)
55 Kenosia Ave., Danbury CT 06810 • (203)744-0100