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Winchester Syndrome

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.


Presentation

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.

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]
  • Patients may also display coarse facial features, and suffer from visual disturbances due to corneal opacification.[symptoma.com]
  • 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]
  • This syndrome is characterized by short stature, arthritis-like symptoms, nodules under the skin (subcutaneous), coarse facial features, and eye and teeth abnormalities.[metrohealth.net]
Pediatric Disorder
  • Definition / general Rare hereditary pediatric disorder with extracellular hyaline material deposition in skin, soft tissue and bone Terminology Molluscum fibrosum in children (original name given by Murray, 1873), mesenchymal dysplasia (Puretic et al[pathologyoutlines.com]
Limited Mobility
  • The painful joints and limited mobility may be mistaken for juvenile rheumatoid arthritis (JRA). A blood test can be done to rule out JRA and other inherited disorders, but there is no specific blood test for Winchester syndrome.[checkorphan.org]
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]
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]
  • 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]
  • Generalized osteoporosis, as well as destruction of bones in the hands and feet, are present. Skin and gum tissue samples (biopsy) are taken and examined under a microscope for changes characteristic of Winchester syndrome.[checkorphan.org]
  • Abstract Torg-Winchester syndrome is an autosomal recessive inherited disease characterized by diffuse osteoporosis and osteolysis due to matrix metalloproteinase-2 (MMP2) enzyme deficiency.[scopemed.org]
Arthralgia
  • 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]
Corneal Opacity
  • 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]
  • 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]
  • 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
  • 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]
  • 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]
  • Keywords Parental Consanguinity Autosomal Inheritance Scheie Syndrome Coarse Face Smooth Muscle Cell Actin These keywords were added by machine and not by the authors.[link.springer.com]
  • 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
  • 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]

Workup

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.

Treatment

  • Treatment - Winchester syndrome 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]
  • This era was followed by improved environmental factors which operate to produce methods of medical treatment, introduction congenital cardiac malformations.[books.google.de]

Prognosis

  • 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]
  • 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]
  • In the literature, the prognosis is generally considered to be good. However, in spinal or thoracic involvement, life-threatening complications can occur [ 10 ]. Management of Gorham-Stout syndrome is also a subject of controversy.[ped-rheum.biomedcentral.com]

Etiology

  • 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]

Epidemiology

  • […] 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]
Sex distribution
Age distribution

Pathophysiology

  • 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

  • Prevention - Winchester syndrome Not supplied. Diagnosis - Winchester syndrome Because Winchester syndrome occurs very rarely, it may be difficult to correctly identify.[checkorphan.org]
  • Prevention There are no current guidelines for preventing Asperger syndrome.[winchesterhospital.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]
  • Author Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public[emedicine.medscape.com]

References

Article

  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.

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Last updated: 2019-06-28 11:26