Winchester syndrome (WS) is a part of an inheritable group of disorders called osteolysis syndromes. It is known to primarily affect the hands and feet, before involving the rest of the skeleton, and is carried in an autosomal recessive pattern. Two other disorders share a similar pathological pattern: Torg syndrome and nodulosis arthropathy osteolysis (NAO) syndrome. Because these conditions have several common features, they have been considered to be part of the same clinical spectrum. WS and Torg syndrome is referred as one disease by some, and NAO is regarded as a variant of the same. All aforementioned conditions are mediated by mutations in the matrix metalloproteinase (MMP) 2 gene, which leads to reduced activity of matrix metalloproteinases.

The first signs of the disease appear in infancy, and their distribution is symmetrical [1]. The skeletal system is the most affected, as the main feature of WS is marked lysis of the bones in the hands and feet. In addition, skeletal deformities, as well as osteoporosis in other bones, has been reported [2]. Patients may also display coarse facial features, and suffer from visual disturbances due to corneal opacification [3] [4] [5].

Other non-skeletal findings include contracture formation, subcutaneous nodules (these appear on the hands), hyperpigmentation, skin thickening, lichenification and banding, abnormally excessive body hair growth (hypertrichosis), myocardial damage, and gum hypertrophy [6] [7].

Arthralgia and loss of function of joints in the hands is a documented complaint. Initially, findings may be almost identical to those of rheumatic arthritis.

• Turkish

  were found in Italian and Algerian families, respectively.9, 10 A compound heterozygous mutation, (c.302G>A)+(c.1357delC), was observed in an American patient.2 Most recently, two homozygous mutations, c.1732delA and c.658+2T>C, were identified in Turkish [nature.com]

• Hypertrichosis

  The cutaneous manifestations of this syndrome include leathery thickening of the skin, hyperpigmentation and hypertrichosis. The lips and gingiva are hypertrophic. There are also arthritic changes involving the small joints. [ncbi.nlm.nih.gov]

  Torg-Winchester syndrome Joe Segen 2016-11-28T07:07:36+00:00 ORTHOPAEDICS An autosomal recessive disorder (OMIM:259600) characterised by generalised osteolysis and osteopenia, coarse face, corneal opacities, patches of thickened, hyperpigmented skin, hypertrichosis [newmedicalterms.com]

  An autosomal recessive syndrome (OMIM:259600) characterised by generalised osteolysis and osteopenia, coarse face, corneal opacities, patches of thickened, hyperpigmented skin, hypertrichosis and gingival hypertrophy. [medical-dictionary.thefreedictionary.com]

• Hyperpigmentation

  The cutaneous manifestations of this syndrome include leathery thickening of the skin, hyperpigmentation and hypertrichosis. The lips and gingiva are hypertrophic. There are also arthritic changes involving the small joints. [ncbi.nlm.nih.gov]

  Other non-skeletal findings include contracture formation, subcutaneous nodules (these appear on the hands), hyperpigmentation, skin thickening, lichenification and banding, abnormally excessive body hair growth (hypertrichosis), myocardial damage, and [symptoma.com]

  […] edit] In 1989, diagnostic criteria was created for the diagnosing of Winchester syndrome.[8] The typical diagnosis criteria begin with skeletal radiological test results and two of the defining symptoms, such as short stature, coarse facial features, hyperpigmentation [en.wikipedia.org]

  / fusion / synostosis - Wrist / carpal anomalies Frequent - Coarse face - Corneal clouding / opacity / vascularisation - Frontal bossing / prominent forehead - Hirsutism / hypertrichosis / Increased body hair - Irregular / in bands / reticular skin hyperpigmentation [csbg.cnb.csic.es]

• Cutaneous Manifestation

  The cutaneous manifestations of this syndrome include leathery thickening of the skin, hyperpigmentation and hypertrichosis. The lips and gingiva are hypertrophic. There are also arthritic changes involving the small joints. [ncbi.nlm.nih.gov]

• Lichenification

  Other non-skeletal findings include contracture formation, subcutaneous nodules (these appear on the hands), hyperpigmentation, skin thickening, lichenification and banding, abnormally excessive body hair growth (hypertrichosis), myocardial damage, and [symptoma.com]

• Hirsutism

  […] mobility / joint stiffness / ankylosis - Short stature / dwarfism / nanism - Tarsal anomaly / fusion / synostosis - Wrist / carpal anomalies Frequent - Coarse face - Corneal clouding / opacity / vascularisation - Frontal bossing / prominent forehead - Hirsutism [csbg.cnb.csic.es]

• Osteoporosis

  On the basis of usefulness of pamidronate in conditions with osteoporosis, we hypothesized that the drug will improve osteolysis and/or osteoporosis in this condition. [ncbi.nlm.nih.gov]

  UniProtKB/Swiss-Prot : 73 Winchester syndrome: A disease characterized by severe osteolysis in the hands and feet, generalized osteoporosis, bone thinning, and absence of subcutaneous nodules. [malacards.org]

• Osteopenia

  Skip to content Torg-Winchester syndrome Joe Segen 2016-11-28T07:07:36+00:00 ORTHOPAEDICS An autosomal recessive disorder (OMIM:259600) characterised by generalised osteolysis and osteopenia, coarse face, corneal opacities, patches of thickened, hyperpigmented [newmedicalterms.com]

  An autosomal recessive syndrome (OMIM:259600) characterised by generalised osteolysis and osteopenia, coarse face, corneal opacities, patches of thickened, hyperpigmented skin, hypertrichosis and gingival hypertrophy. [medical-dictionary.thefreedictionary.com]

  Most people with Winchester syndrome develop low bone mineral density (osteopenia) and thinning of the bones (osteoporosis) throughout the skeleton. These abnormalities make bones brittle and more prone to fracture. [malacards.org]

  Osteopenia and osteolysis At present no specific therapy can alleviate the progressive osteopenia. Assure that daily requirements of vitamin D and calcium are met. [ncbi.nlm.nih.gov]

  Many people develop osteopenia and osteoporosis throughout their entire body. [en.wikipedia.org]

• Joint Stiffness

  The syndrome is characterized by short stature, coarse face, corneal opacities, generalized osteolysis and progressive painful arthropathy with joint stiffness and contractures of distal phalanges in combination with skin changes. [ncbi.nlm.nih.gov]

  […] mobility / joint stiffness / ankylosis - Short stature / dwarfism / nanism - Tarsal anomaly / fusion / synostosis - Wrist / carpal anomalies Frequent - Coarse face - Corneal clouding / opacity / vascularisation - Frontal bossing / prominent forehead [csbg.cnb.csic.es]

• Small Hand

  A 31-year-old female Korean patient had the typical clinical phenotypes of the syndrome, including shortening of trunk and limbs and severe osteolysis resulting in extremely small hands and feet. [ncbi.nlm.nih.gov]

• Joint Swelling

  […] diaphyseal dysplasia) (.1555) Epiphyseal acrodysplasia (Thiemann) (.1538) Erb's palsy F Fabry disease (.679) Fanconi anemia (radial ray) (.653) Fanconi syndrome (Renal tubular osteodystrophy) (.5723) Farber disease (disseminated lipogranulomatosis, joint [bonepit.com]

• Corneal Opacity

  Various additional features include coarse face, corneal opacities, gum hypertrophy, and EKG changes. Wikipedia : 74 Winchester syndrome is a rare congenital connective tissue disease described in 1969, of which the main... more... [malacards.org]

  The syndrome is characterized by short stature, coarse face, corneal opacities, generalized osteolysis and progressive painful arthropathy with joint stiffness and contractures of distal phalanges in combination with skin changes. [ncbi.nlm.nih.gov]

  Skip to content Torg-Winchester syndrome Joe Segen 2016-11-28T07:07:36+00:00 ORTHOPAEDICS An autosomal recessive disorder (OMIM:259600) characterised by generalised osteolysis and osteopenia, coarse face, corneal opacities, patches of thickened, hyperpigmented [newmedicalterms.com]

• Coarse Face

  Various additional features include coarse face, corneal opacities, gum hypertrophy, and EKG changes. Wikipedia : 76 Winchester syndrome is a rare congenital connective tissue disease described in 1969, of which the main... more... [malacards.org]

  Winchester syndrome: subcutaneous nodules are characteristically absent, severe osteolysis in the hands and feet, and various additional features including coarse face, corneal opacities, gum hypertrophy, and EKG coarse face Main biochemical alterations [iofbonehealth.org]

  The syndrome is characterized by short stature, coarse face, corneal opacities, generalized osteolysis and progressive painful arthropathy with joint stiffness and contractures of distal phalanges in combination with skin changes. [ncbi.nlm.nih.gov]

  Skip to content Torg-Winchester syndrome Joe Segen 2016-11-28T07:07:36+00:00 ORTHOPAEDICS An autosomal recessive disorder (OMIM:259600) characterised by generalised osteolysis and osteopenia, coarse face, corneal opacities, patches of thickened, hyperpigmented [newmedicalterms.com]

• Abnormal Gait

  […] shaft Metabolic Abnormality Elevated IL1-beta Elevated IL6 Elevated antinuclear antibody (ANA) (speckled pattern) Performance Abnormal gait Skeletal Carpal osteolysis Fusiform finger swelling Interphalangeal joint erosions Osteoporosis Pes planus Show [datagenno.com]

  At the age of 18 months, her parents observed an abnormal gait and an element of contractures appeared. [ped-rheum.biomedcentral.com]

No specific diagnostic tests are available for Winchester syndrome. Biochemical studies that are requested are carried out in order to exclude metabolic and storage diseases such as mucopolysaccharidosis and mucolipidosis, as well as autoimmune disorders, particularly rheumatoid arthritis [1] [8].

As the primary pathological processes taking place are bone destruction and resorption, radiography is the chief investigation in cases of WS because it allows visualization of varying degrees of bone and joint pathology, which are in direct proportion to the duration of the illness. These appear on film as osteolytic lesions affecting carpal, metacarpal and phalangeal bones (and corresponding bones in the feet), as well as widespread reduced bone density. Further characteristic features include metaphyseal and epiphyseal abnormalities of the long bones and medullary cavity expansion. One of the overall results of the skeletal damage described is ankylosis.

Histological analysis of biopsy samples from skin lesions further consolidates the diagnosis. Basic histological images show elevated melanin and inflammatory cell levels in the deeper layers of the skin. Electron microscopy reveals fibroblast changes in form of abnormal mitochondria and various cell organelles.

There have only been a few individuals worldwide who were reported to have this disorder.[3] Treatment[edit] There is no known cure for Winchester syndrome; however, there are many therapies that can aid in the treatment of symptoms.[4] Such treatments [en.wikipedia.org]

Treatment There is no treatment available to stop or reverse Winchester syndrome, so treatment focuses on relieving symptoms. [checkorphan.org]

Specific medications that can help significantly are ropinrole (this is also used in the treatment of Parkinson’s disease) and its close relatives; they are licensed for the treatment of RLS. [winchestergp.com]

Prognosis - Winchester syndrome Not supplied. Treatment - Winchester syndrome There is no treatment available to stop or reverse Winchester syndrome, so treatment focuses on relieving symptoms. [checkorphan.org]

The prognosis for patients diagnosed with Winchester syndrome is positive. It has been reported that several affected individuals have lived to middle age; however, the disease is progressive and mobility will become limited towards the end of life. [en.wikipedia.org]

The etiology is unknown. Parental consanguinity supports autosomal inheritance. The diagnosis is based on clinical and radiological manifestations. We describe a case in a 7-year-old Pakistani boy. [ncbi.nlm.nih.gov]

Their etiology is not precisely century with the first clinical recognition of known, so we have included chapters that dis symptoms and patterns for diagnosis of car cuss many aspects of congenital cardiac mal diovascular diseases. [books.google.de]

Torg syndrome is a multicentric osteolysis syndrome of unknown etiology. We identified mutations in the MMP2 gene in a patient with Torg syndrome that resulted in complete loss of MMP2 activity. [wikigenes.org]

[…] telangiectasia Synonym(s): - Winchester syndrome Classification (Orphanet): - Rare bone disease - Rare developmental defect during embryogenesis - Rare genetic disease Classification (ICD10): - Diseases of the musculoskeletal system and connective tissue - Epidemiological [csbg.cnb.csic.es]

Mutat 2009;30:583 ) "Hyaline fibromatosis syndrome" proposed as an umbrella term for juvenile hyaline fibromatosis and infantile systemic hyalinosis since the two syndromes have significant clinicopathologic overlap ( J Am Acad Dermatol 2009;61:695 ) Epidemiology [pathologyoutlines.com]

Epidemiology Frequency United States In the United States, 3 cases were described. International Cases in 3 Mexican patients are described (published in the United States). [emedicine.medscape.com]

2018 International Expert Consensus Document on Takotsubo Syndrome (Part Ii): Diagnostic Workup, Outcome, and Management 2018 International Expert Consensus Document on Takotsubo Syndrome (Part I): Clinical Characteristics, Diagnostic Criteria, and Pathophysiology [ufhealth.org]

Pathophysiology Winchester syndrome appears to be inherited in an autosomal recessive manner. [2, 12] The specific cause of the changes has not been clarified. [emedicine.medscape.com]

The disease pathophysiology commences with intramedullary and subcortical radiolucent foci resembling patchy osteoporosis. It makes slow, irregular, local progress with a concentric shrinkage of the shafts of the bones. [ped-rheum.biomedcentral.com]

Prevention You cannot always prevent dumping syndrome. Dietary adjustments may decrease the severity and prevent recurrences of your symptoms. Other Resources The Zone Diet® by Dr. Barry Sears or the South Beach Diet® by Dr. [winchestergastro.com]

Prevention Since FAS is closely linked to stroke, follow these guidelines to prevent stroke: Exercise regularly. Eat a healthful diet. If you smoke, talk to your doctor about ways to quit. Drink alcohol only in moderation. [winchesterhospital.org]

Prevention - Winchester syndrome Not supplied. Diagnosis - Winchester syndrome Because Winchester syndrome occurs very rarely, it may be difficult to correctly identify. [checkorphan.org]

To have strong bones when you are young, and to prevent bone loss when you are older, you need to get enough calcium, vitamin D, and exercise. You should also avoid smoking and drinking too much alcohol. Bone diseases can make bones easy to break. [medlineplus.gov]

1. Prapanpoch S, Jorgenson RJ, Langlais RP, Nummikoski PV. Winchester syndrome. A case report and literature review. Oral Surg Oral Med Oral Pathol. 1992;74(5):671-677.
2. Sidwell RU, Brueton LA, Grabczynska SA, Francis N, Staughton RCD. Progressive multilayered banded skin in Winchester syndrome. J Am Acad Dermatol. 2004;50(2 Suppl): S53-S56.
3. Hall CM. International nosology and classification of constitutional disorders of bone (2001). Am J Med Genet. 2002;113(1):65–77.
4. Zankl A, Bonafe L, Calcaterra V, Di Rocco M, Superti-Furga. A 2005 Winchester syndrome caused by a homozygous mutation affecting the active site of matrix metalloproteinase 2. Clin Genet. 2005;67(3): 261–266.
5. Zankl A, Pachman L, Poznanski A, et al. Torg syndrome is caused by inactivating mutations in MMP2 and is allelic to NAO and Winchester syndrome. J Bone Miner Res. 2007;22(2):329–333.
6. Superti-Furga A, Unger S. Nosology and classification of genetic skeletal disorders: 2006 revision. Am J Med Genet A. 2007;143A(1):1-18.
7. Phadke SR, Ramirez M, Difeo A, Martignetti JA, Girisha KM. Torg-Winchester syndrome: lack of efficacy of pamidronate therapy. Clin Dysmorphol. 2007;16(2):95-100.
8. Nabai H, Mehregan AH, Mortezai A, Alipour P, Karimi FZ. Winchester syndrome: report of a case from Iran. J Cutan Pathol. 1977;4(5):281-285.