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Winchester syndrome(WNCHRS)

MedGen UID:
98152
Concept ID:
C0432289
Disease or Syndrome
Synonym: WNCHRS
SNOMED CT: Winchester syndrome (254151006)
 
Gene (location): MMP14 (14q11.2)
 
Monarch Initiative: MONDO:0010201
OMIM®: 277950

Definition

Winchester syndrome (WNCHRS) presents with severe osteolysis in the hands and feet and generalized osteoporosis and bone thinning, similar to multicentric osteolysis, nodulosis, and arthropathy (MONA; 259600), but subcutaneous nodules are characteristically absent. Various additional features including coarse face, corneal opacities, gum hypertrophy, and EKG changes have been reported (summary by Zankl et al., 2007). Reviews Winter (1989) provided a review of Winchester syndrome. De Vos et al. (2019) reviewed Winchester syndrome, Frank-Ter Haar syndrome (249420), and MONA, tabulating the clinical features of 63 reported patients and noting significant overlap, including craniofacial malformations, reduced bone density, skeletal and cardiac anomalies, and dermal fibrosis. Because the protein products of all 3 causative genes (MMP14; SH3PXD2B, 613293; MMP2, 120360) are involved in collagen remodeling, the authors suggested grouping them together in a revised nosologic classification, designated 'defective collagen-remodeling spectrum (DECORS).' [from OMIM]

Additional description

From MedlinePlus Genetics
Winchester syndrome is a rare inherited disease characterized by a loss of bone tissue (osteolysis), particularly in the hands and feet. Winchester syndrome used to be considered part of a related condition now called multicentric osteolysis, nodulosis, and arthropathy (MONA). However, because Winchester syndrome and MONA are caused by mutations in different genes, they are now thought to be separate disorders.

In most cases of Winchester syndrome, bone loss begins in the hands and feet, causing pain and limiting movement. Bone abnormalities later spread to other parts of the body, with joint problems (arthropathy) occurring in the elbows, shoulders, knees, hips, and spine. 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. The bone abnormalities also lead to short stature.

Some people with Winchester syndrome have skin abnormalities including patches of dark, thick, and leathery skin. Other features of the condition can include clouding of the clear front covering of the eye (corneal opacity), excess hair growth (hypertrichosis), overgrowth of the gums, heart abnormalities, and distinctive facial features that are described as "coarse."  https://medlineplus.gov/genetics/condition/winchester-syndrome

Clinical features

From HPO
Carpal osteolysis
MedGen UID:
318954
Concept ID:
C1833734
Pathologic Function
Osteolysis affecting carpal bones.
Osteolysis involving tarsal bones
MedGen UID:
322262
Concept ID:
C1833735
Pathologic Function
An increased resorption of bone matrix by osteoclasts leading to bony defects involving the tarsal bones.
Broad metacarpals
MedGen UID:
330796
Concept ID:
C1842229
Finding
Abnormally broad metacarpal bones.
Arthropathy
MedGen UID:
7190
Concept ID:
C0022408
Disease or Syndrome
Any disorder of the joints.
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Exaggerated anterior convexity of the thoracic vertebral column.
Generalized osteoporosis
MedGen UID:
1639139
Concept ID:
C4551680
Disease or Syndrome
Gingival overgrowth
MedGen UID:
87712
Concept ID:
C0376480
Finding
Hyperplasia of the gingiva (that is, a thickening of the soft tissue overlying the alveolar ridge. The degree of thickening ranges from involvement of the interdental papillae alone to gingival overgrowth covering the entire tooth crown.
Coarse facial features
MedGen UID:
335284
Concept ID:
C1845847
Finding
Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues.
Hirsutism
MedGen UID:
42461
Concept ID:
C0019572
Disease or Syndrome
Abnormally increased hair growth referring to a male pattern of body hair (androgenic hair).
Subcutaneous nodule
MedGen UID:
101803
Concept ID:
C0151811
Pathologic Function
Slightly elevated lesions on or in the skin with a diameter of over 5 mm.
Corneal opacity
MedGen UID:
40485
Concept ID:
C0010038
Finding
A reduction of corneal clarity.

Recent clinical studies

Etiology

Salam H, Shahid R, Mirza T
J Coll Physicians Surg Pak 2017 Sep;27(9):S89-S91. PMID: 28969735
Bhavani GS, Shah H, Shukla A, Gupta N, Gowrishankar K, Rao AP, Kabra M, Agarwal M, Ranganath P, Ekbote AV, Phadke SR, Kamath A, Dalal A, Girisha KM
Am J Med Genet A 2016 Feb;170A(2):410-417. Epub 2015 Nov 24 doi: 10.1002/ajmg.a.37447. PMID: 26601801
Evans BR, Mosig RA, Lobl M, Martignetti CR, Camacho C, Grum-Tokars V, Glucksman MJ, Martignetti JA
Am J Hum Genet 2012 Sep 7;91(3):572-6. Epub 2012 Aug 23 doi: 10.1016/j.ajhg.2012.07.022. PMID: 22922033Free PMC Article
Zankl A, Pachman L, Poznanski A, Bonafé L, Wang F, Shusterman Y, Fishman DA, Superti-Furga A
J Bone Miner Res 2007 Feb;22(2):329-33. doi: 10.1359/jbmr.061013. PMID: 17059372
Matthiesen G, Pedersen VF, Helin P, Jacobsen GK, Nielsen NS
Int Orthop 2001;25(5):331-3. doi: 10.1007/s002640100276. PMID: 11794271Free PMC Article

Diagnosis

de Vos IJHM, Wong ASW, Welting TJM, Coull BJ, van Steensel MAM
Am J Med Genet A 2019 Aug;179(8):1652-1664. Epub 2019 Jun 19 doi: 10.1002/ajmg.a.61264. PMID: 31218820
Salam H, Shahid R, Mirza T
J Coll Physicians Surg Pak 2017 Sep;27(9):S89-S91. PMID: 28969735
Matthiesen G, Pedersen VF, Helin P, Jacobsen GK, Nielsen NS
Int Orthop 2001;25(5):331-3. doi: 10.1007/s002640100276. PMID: 11794271Free PMC Article
Tyler T, Rosenbaum HD
AJR Am J Roentgenol 1976 Jan;126(1):23-31. doi: 10.2214/ajr.126.1.23. PMID: 175680
Hollister DW, Rimoin DL, Lachman RS, Westin GW, Cohen AH
Birth Defects Orig Artic Ser 1974;10(10):89-100. PMID: 4462644

Therapy

Dash G, Pradhan S, Sinha U, Sinha R
Pediatr Dermatol 2024 Jul-Aug;41(4):688-691. Epub 2024 Jan 30 doi: 10.1111/pde.15543. PMID: 38291559
Li ZC, Huang MH, Zhong WQ, Liu ZQ, Xie Y, Dai Z, Zou XY
Bioinformatics 2016 Apr 1;32(7):1057-64. Epub 2015 Nov 26 doi: 10.1093/bioinformatics/btv695. PMID: 26614126
Phadke SR, Ramirez M, DiFeo A, Martignetti JA, Girisha KM
Clin Dysmorphol 2007 Apr;16(2):95-100. doi: 10.1097/MCD.0b013e3280147187. PMID: 17351352
Matthiesen G, Pedersen VF, Helin P, Jacobsen GK, Nielsen NS
Int Orthop 2001;25(5):331-3. doi: 10.1007/s002640100276. PMID: 11794271Free PMC Article

Prognosis

Li ZC, Huang MH, Zhong WQ, Liu ZQ, Xie Y, Dai Z, Zou XY
Bioinformatics 2016 Apr 1;32(7):1057-64. Epub 2015 Nov 26 doi: 10.1093/bioinformatics/btv695. PMID: 26614126
Bhavani GS, Shah H, Shukla A, Gupta N, Gowrishankar K, Rao AP, Kabra M, Agarwal M, Ranganath P, Ekbote AV, Phadke SR, Kamath A, Dalal A, Girisha KM
Am J Med Genet A 2016 Feb;170A(2):410-417. Epub 2015 Nov 24 doi: 10.1002/ajmg.a.37447. PMID: 26601801
Ekbote AV, Danda S, Zankl A, Mandal K, Maguire T, Ungerer K
J Clin Res Pediatr Endocrinol 2014;6(1):40-6. doi: 10.4274/Jcrpe.1166. PMID: 24637309Free PMC Article
Matthiesen G, Pedersen VF, Helin P, Jacobsen GK, Nielsen NS
Int Orthop 2001;25(5):331-3. doi: 10.1007/s002640100276. PMID: 11794271Free PMC Article

Clinical prediction guides

de Vos IJHM, Tao EY, Ong SLM, Goggi JL, Scerri T, Wilson GR, Low CGM, Wong ASW, Grussu D, Stegmann APA, van Geel M, Janssen R, Amor DJ, Bahlo M, Dunn NR, Carney TJ, Lockhart PJ, Coull BJ, van Steensel MAM
Hum Mol Genet 2018 Aug 15;27(16):2775-2788. doi: 10.1093/hmg/ddy168. PMID: 29741626Free PMC Article
Li ZC, Huang MH, Zhong WQ, Liu ZQ, Xie Y, Dai Z, Zou XY
Bioinformatics 2016 Apr 1;32(7):1057-64. Epub 2015 Nov 26 doi: 10.1093/bioinformatics/btv695. PMID: 26614126
Rouzier C, Vanatka R, Bannwarth S, Philip N, Coussement A, Paquis-Flucklinger V, Lambert JC
Clin Genet 2006 Mar;69(3):271-6. doi: 10.1111/j.1399-0004.2006.00584.x. PMID: 16542393

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