Winchester syndrome is a genetic disorder inherited in an autosomal recessive pattern. It involves the lysis of bones in the hands and feet, as well as additional skeletal abnormalities. The disease is closely associated with other osteolytic disorders.
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 . 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 . Patients may also display coarse facial features, and suffer from visual disturbances due to corneal opacification   .
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  .
Entire Body System
- Coarse Facial Features
The syndrome is characterized by dissolution of carpal and tarsal bones with generalized osteoporosis, progressive joint contractures, short stature, peripheral corneal opacities, and coarse facial features, though there is variability within the clinical [ncbi.nlm.nih.gov]
This syndrome is characterized by short stature, arthritis-like symptoms, nodules under the skin (subcutaneous), coarse facial features, and eye and teeth abnormalities. [rarediseases.org]
Affiliated tissues include bone, skin and testes, and related phenotypes are gingival overgrowth and coarse facial features OMIM : 57 Winchester syndrome presents with severe osteolysis in the hands and feet and generalized osteoporosis and bone thinning [malacards.org]
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]
- 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]
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]
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. No specific diagnostic tests are available for Winchester syndrome. [symptoma.com]
- Back Pain
She complained of progressive back pain and tingling sensations in the upper extremities. [nature.com]
- Abnormal Gait
Signs / Symptoms (17) Feet Pes cavus Show images Joints and Tendons Joint contractures Limbs Abnormality Widened metacarpal shaft Metabolic Abnormality Elevated IL1-beta Elevated IL6 Elevated antinuclear antibody (ANA) (speckled pattern) Performance Abnormal [datagenno.com]
At the age of 18 months, her parents observed an abnormal gait and an element of contractures appeared. [ped-rheum.biomedcentral.com]
- Poor Coordination
coordination Inflexibility or trouble accepting change Difficulty accepting loss or criticism Obsessive desire to finish any tasks that are started Diagnosis There are no tests for Asperger syndrome. [winchesterhospital.org]
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  .
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.
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]
Deering can design a treatment plan to help relieve your symptoms. For people with otherwise normal eyes and vision, a set of specially-designed glasses used during the time you are working on the computer can be very helpful. [winchesteroptical.net]
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 knowledge may provide valuable information in the aspect of prognosis and future management of the syndrome. [nature.com]
Medicine and Research 2019 Using Simulation to Teach Echocardiography: A Systematic Review Simulation in Healthcare-Journal of the Society for Simulation in Healthcare 2018 Proposed mechanisms of relative bradycardia Medical Hypotheses 2018 Long-Term Prognosis [ufhealth.org]
Prognosis The disease has a progressive course with aggravating bony-articular, ocular, and cutaneous changes. Evans BR, Mosig RA, Lobl M, Martignetti CR, Camacho C, Grum-Tokars V, et al. [emedicine.medscape.com]
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]
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]
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]
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 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]
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]
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]
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- 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.
- Hall CM. International nosology and classification of constitutional disorders of bone (2001). Am J Med Genet. 2002;113(1):65–77.
- 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.
- 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.
- Superti-Furga A, Unger S. Nosology and classification of genetic skeletal disorders: 2006 revision. Am J Med Genet A. 2007;143A(1):1-18.
- 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.
- 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.