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]

  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]

• 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]

• 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]

  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

  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]

• 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]

• 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]

• 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 [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.

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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.