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Am J Med Genet A 2019 08 19;179(8):1652-1664. Epub 2019 Jun 19.

Skin Research Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.

Frank-Ter Haar syndrome (FTHS), Winchester syndrome (WS), and multicentric osteolysis, nodulosis, and arthropathy (MONA) are ultra-rare multisystem disorders characterized by craniofacial malformations, reduced bone density, skeletal and cardiac anomalies, and dermal fibrosis. These autosomal recessive syndromes are caused by homozygous mutation or deletion of respectively SH3PXD2B (SH3 and PX Domains 2B), MMP14 (matrix metalloproteinase 14), or MMP2. Here, we give an overview of the clinical features of 63 previously reported patients with an SH3PXD2B, MMP14, or MMP2 mutation, demonstrating considerable clinical overlap between FTHS, WS, and MONA. Read More

Hum Mol Genet 2018 08;27(16):2775-2788

Institute of Medical Biology (IMB), Agency for Science, Technology and Research (A*STAR), Singapore 138648, Singapore.

Winchester syndrome (WS, MIM #277950) is an extremely rare autosomal recessive skeletal dysplasia characterized by progressive joint destruction and osteolysis. To date, only one missense mutation in MMP14, encoding the membrane-bound matrix metalloprotease 14, has been reported in WS patients. Here, we report a novel hypomorphic MMP14 p. Read More

J Coll Physicians Surg Pak 2017 Sep;27(9):S89-S91

Department of Pathology, Dow International Medical College, Dow University of Health Sciences, Ojha Campus, Karachi.

Langerhans cell histiocytosis (LCH) is the latest terminology for a disorder of reticulo-endothelial system, previously known as histiocytosis X, and marked by aberrant proliferation of bone marrow derived Langerhans cells with variable inflammatory infiltrate including neutrophils, lymphocytes, plasma cells, eosinophils, and multinucleated giant cells. Although rare, the disorder frequently inflicts children with peak incidence recorded in 2-4 years age group. LCH is rare in adults. Read More

Bioinformatics 2016 04 26;32(7):1057-64. Epub 2015 Nov 26.

SYSU-CMU Shunde International Joint Research Institute, Shunde 528300, People's Republic of China and School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, People's Republic of China.

Motivation: Identifying drug-target protein interaction is a crucial step in the process of drug research and development. Wet-lab experiment are laborious, time-consuming and expensive. Hence, there is a strong demand for the development of a novel theoretical method to identify potential interaction between drug and target protein. Read More

Am J Med Genet A 2016 Feb 24;170A(2):410-417. Epub 2015 Nov 24.

Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal, India.

​Multicentric osteolysis nodulosis and arthropathy (MONA) is an infrequently described autosomal recessive skeletal dysplasia characterized by progressive osteolysis and arthropathy. Inactivating mutations in MMP2, encoding matrix metalloproteinase-2, are known to cause this disorder. Fifteen families with mutations in MMP2 have been reported in literature. Read More

J Oral Maxillofac Surg 2015 Oct 8;73(10):1962.e1-5. Epub 2015 Jul 8.

Resident, Dental Surgery Clinic, Children's Memorial Health Institute, Warsaw, Poland.

Infantile systemic hyalinosis (ISH) is a rare autosomal recessive disorder caused by a mutation in the ANTXR2 gene encoding a transmembranous protein involved in endothelial development. The ANTXR2 (also known as CMG2) locus is on chromosome 4q21. ISH is a common disorder in children of consanguineous parents in Arab countries. Read More

J Clin Res Pediatr Endocrinol 2014 ;6(1):40-6

Christian Medical College, Clinical Genetics Unit, Vellore, India. E-ma-il:

Torg and Winchester syndromes and patients reported by Al-AqeelSawairi as well as nodulosis-arthropathy-osteolysis (NAO) patients, patients with multicentric NAO share autosomal recessive inheritance. The common presenting symptomatology includes progressive osteolysis chiefly affecting the carpal, tarsal and interphalangeal joints. Here, we report a patient with Torg syndrome. Read More

Am J Hum Genet 2012 Sep 23;91(3):572-6. Epub 2012 Aug 23.

Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, USA.

The "vanishing bone" syndromes represent a group of rare skeletal disorders characterized by osteolysis and joint destruction, which can mimic severe rheumatoid arthritis. Winchester syndrome was one of the first recognized autosomal-recessive, multicentric forms of the disorder. It was originally described nearly 50 years ago in two sisters with a severe crippling osteolysis. Read More

Genet Couns 2012 ;23(2):175-84

Department of Clinical Genetics, Human Genetics & Genome Research Division, National Research Centre, Cairo, Egypt.

Osteolysis syndromes are rare hereditary disorders characterized by destruction and resorption of affected bones. The current study adds three new patients from two unrelated consanguineous families with a severe form of inherited osteolysis. Clinical examination, radiological, biochemical, ultrastructural and molecular studies were conducted. Read More

Pediatr Rheumatol Online J 2011 Oct 13;9:31. Epub 2011 Oct 13.

Ludwig-Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, First Medical Department, Hanusch Hospital, Vienna, Austria.

Idiopathic osteolysis or disappearing bone disease is a condition characterized by the spontaneous onset of rapid destruction and resorption of a single bone or multiple bones. Disappearing bone disorder is a disease of several diagnostic types. We are presenting three patients with osteolysis who have different underlying pathological features. Read More

Skeletal Radiol 2011 Mar 24;40(3):347-51. Epub 2010 Sep 24.

Department of Radiology, University Hospital Bratislava, Antolska 11, 851 07, Bratislava, Slovak Republic.

Winchester syndrome (WS) is a rare autosomal recessive syndrome resulting in multicentric osteolysis. Only a few cases of WS have been described in the literature worldwide. It has recently been shown to be caused by mutation in the gene encoding matrix metalloproteinase-2 (MMP2). Read More

J Hum Genet 2010 Nov 19;55(11):764-6. Epub 2010 Aug 19.

Department of Medical Genetics, School of Medicine, Ajou University, Suwon, Korea.

Torg-Winchester syndrome (OMIM 259600) is an autosomal recessive multicentric osteolysis disorder. Mutations in the gene for matrix metalloproteinase 2 (MMP2) are involved in its pathogenesis. This is the first report of Torg-Winchester syndrome in east Asians. Read More

Eur J Pediatr 2010 Mar 4;169(3):363-7. Epub 2009 Aug 4.

Department of Pediatric Nephrology and Rheumatology, Gulhane Military Medical Academy, School of Medicine, 06018 Etlik, Ankara, Turkey.

The two well-described osteolysis syndromes associated with matrix metalloproteinase-2 deficiency and mutations in the metalloproteinase-2 gene are Torg-Winchester syndrome and nodulosis-arthropathy-osteolysis variant. They are characterized by carpal-tarsal destruction, subcutaneous nodules, and generalized osteoporosis and show autosomal recessive inheritance. Herein, we report two siblings affected with a novel mutation in matrix metalloproteinase 2 gene and discuss their clinical and radiographic findings. Read More

Int J Dermatol 2009 Feb;48(2):175-7

Department of Dermatology, Armed Forces Medical College, Pune, India.

Clin Dysmorphol 2007 Apr;16(2):95-100

Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

Torg-Winchester syndrome, which includes nodular arthropathy with osteolysis (OMIM 605156), is a condition associated with generalized 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. After obtaining informed consent from the parents, two siblings affected with Torg-Winchester syndrome were administered intravenous pamidronate over a period of 3 years. Read More

J Bone Miner Res 2007 Feb;22(2):329-33

CHUV, Lausanne, Switzerland.

Unlabelled: 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. MMP2 mutations were previously identified in patients with NAO and Winchester syndrome. Read More

Clin Genet 2006 Mar;69(3):271-6

Department of Medical Genetics, Archet 2 Hospital, CHU Nice, France.

The 2001 International Classification of Constitutional Disorders of Bone has included in the group of multicentric hands and feet osteolysis syndromes three autosomal recessive inherited disorders: Winchester, Torg and nodulosis-arthropathy-osteolysis (NAO) syndromes. Nosographic delineations of these rare syndromes are difficult to define, and there is no consensus. In 2001, two mutations in the matrix metalloproteinase 2 gene (MMP2) have been identified in two families with a NAO phenotype. Read More

Clin Genet 2005 Mar;67(3):261-6

Division of Molecular Pediatrics, Center Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland.

The inherited osteolysis syndromes are a heterogeneous group of skeletal disorders whose classification is still uncertain. Three osteolysis syndromes show autosomal recessive inheritance and multicentric involvement: Torg syndrome (OMIM 259600), Winchester syndrome (OMIM 277950) and Nodulosis-Arthropathy-Osteolysis syndrome (NAO; OMIM 605156). The 2001 Nosology of the International Skeletal Dysplasia Society (Hall CM, Am J Med Genet 2002: 113: 65) classifies NAO as a variant of Torg syndrome, while Winchester syndrome is considered as a separate disorder. Read More

J Am Acad Dermatol 2004 Feb;50(2 Suppl):S53-6

Department of Dermatology (Hammersmith Hospitals Trust), Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK.

Winchester syndrome is a rare genetic disorder, one of the inherited osteolysis disorders which are a group of diseases characterized by destruction and resorption of affected bones with consequent skeletal deformities and functional impairment. 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 features. Phenotypic heterogeneity of cutaneous features are also reported to date of diffusely thickened leathery skin, hypertrichosis, patches of hyperpigmented, hypertrichotic leathery skin in annular or linear distribution, widespread acne, subcutaneous nodules, and gingival hypertrophy. Read More

Int Orthop 2001 ;25(5):331-3

Department of Pediatrics, Glostrup University Hospital, Denmark.

Winchester syndrome was first described in 1969 and since then nine patients have been reported in the literature. 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. The etiology is unknown. Read More

Ryoikibetsu Shokogun Shirizu 2001 (34 Pt 2):817-8

Division of Medical Genetics, Kanagawa Children's Medical Center/Department of Pediatrics, Tokyo Women's Medical University.

Oral Surg Oral Med Oral Pathol 1992 Nov;74(5):671-7

Department of Dental Diagnostic Science, University of Texas Health Science Center, San Antonio.

The mucopolysaccharidoses are a group of inherited lysosomal storage diseases that are caused by a deficiency of specific enzymes. The acid mucopolysaccharides are stored in tissue and excreted in large quantities in the urine. The storage of this material leads to effects on a wide variety of tissues and to remarkable changes in morphologic features. Read More

J Genet Hum 1989 Sep;37(3):231-6

Unité de Génétique Médicale du CHU de Nice.

Two new familial cases of Winchester syndrome with the characteristic features allowed to be more explicit on a few data of this syndrome. As reported in a previous paper an abnormal oligosaccharide was detected in urine of patients but the pathological significance of this oligosaccharide must be discussed and its finding in patients with Winchester syndrome does not lead to further elucidation of the aetiology of this condition. Cultured fibroblasts were obtained from a skin biopsy performed in thickened area. Read More

Eur J Pediatr 1987 Nov;146(6):615-9

Hospital for Sick Children, London, UK.

We present our findings in two unrelated patients with the characteristic clinical and radiological features of the Winchester syndrome. The histological findings in gum and skin biopsies taken from one of the subjects, indicated excessive collagen turnover (active phagocytosis, an active endoplasmic reticulum, and an abundance of fibrillogranular material of probable collagen origin). An abnormal oligosaccharide was detected in urine from both patients which was identified as a trisaccharide containing one fucose and two galactose residues. Read More

Clin Radiol 1983 Sep;34(5):585-8

A family is described which has exhibited in four generations a bizarre form of arthritis mutilans and osteolysis, the features of which seem to fit most closely with a diagnosis of hereditary multicentric osteolysis, a subgroup of idiopathic multicentric osteolysis. The differential diagnosis of arthritis mutilans associated with osteolysis is discussed; this includes a wide variety of disorders ranging from rheumatoid arthritis to rare conditions such as the Winchester syndrome. Read More

Indian Pediatr 1978 Oct;15(10):861-3

J Cutan Pathol 1977 Oct;4(5):281-5

A child with Winchester syndrome, studied in Iran, is the sixth reported case in the literature. The cutaneous manifestations of this syndrome include leathery thickening of the skin, hyperpigmentation and hypertrichosis. The lips and gingiva are hypertrophic. Read More

AJR Am J Roentgenol 1976 Jan;126(1):23-31

A 59 year old while female with striking carpal and tarsal osteolysis is reported. The process primarily involves the carpals and tarsals but includes other sites. The pertinent literature is reviewed and a simplified classification of idiopathic multicentric osteolysis is presented. Read More

J Pediatr 1975 Apr;86(4):646-7

Arch Dermatol 1975 Feb;111(2):230-6

The Winchester syndrome, a rare inherited disorder, is characterized by dwarfism, carpal-tarsal osteolysis, rheumatoid-like small joint destruction, corneal opacities, and thickening and hypertrichosis of the skin, unlike that seen in other genodermatoses. The early stages of cutaneous abnormalities are characterized by proliferation of fibroblasts deep in the dermis, while hypocellular homogenization of the collagen is evident later. Ultrastructural peculiarities of fibroblasts include dilated and vacuolated mitochondria, the presence of varying amounts of myofilaments in the cytoplasm, and a prominent fibrous nuclear lamina. Read More

J Pediatr 1974 May;84(5):701-9

Birth Defects Orig Artic Ser 1974 ;10(10):89-100