GARD :
20
The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 371428DefinitionA rare systemic or rheumatologic disease characterized by peripheral osteolysis (especially carpal and tarsal bones), interphalangeal joint erosions, subcutaneous fibrocollagenous nodules, facial dysmorphism, and a wide range of associated manifestations.EpidemiologyMulticentric osteolysis-nodulosis-arthropathy (MONA) spectrum prevalence and incidence of MONA are not known. Fewer than 50 cases have been reported worldwide. Cases have been reported from Saudi Arabia, Italy, Turkey, Algeria, Morocco, the United States, and Korea.Clinical descriptionOnset is usually at preschool age (1-5 years) and the course of the disease is variable. Manifestations of the disorder include multiple peripheral osteolysis beginning at the carpal, tarsal, metacarpal/metatarsal-phalangeal and interphalangeal joints with subsequent generalization. The joint erosions lead to small hands and feet, arthropathy causing decreased range of motion, and progressive joint contractures. Some patients have been reported to have wide metacarpals and metatarsals, generalized osteoporosis of vertebrae, short stature, coarse face or facial dysmorphism (frontal bossing and hypertelorism), gum hypertrophy, corneal opacities, hyperpigmentation, hypertrichosis, and subcutaneous fibrocollagenous nodules. Associated cardiac malformations have been reported and included transposition of the great arteries, mitral valve prolapse, bicuspid aortic valve, and atrial and ventricular septal defects. Intrafamilial variability of manifestations is also found. Due to overlapping clinical features and the involvement of mutations in MMP2gene, Torg-Winchester syndrome and nodulosis-arthropathy-osteolysis (NAO) syndromes, that were originally reported separately, are now presumed to belong to the clinical spectrum of MONA (with other nomenclatures still being is use).EtiologyMONA spectrum disorders are caused by mutations in the MMP2 gene (16q13-q21) or MMP14 gene (14q11-q12). The pathogenesis of the disorder remains unclear.Diagnostic methodsThe diagnosis is based on the clinical manifestations of the disease and can be confirmed by molecular genetic testing.Differential diagnosisThe main differential diagnoses are juvenile idiopathic arthritis and multicentric carpotarsal osteolysis.Genetic counselingMONA spectrum disorders follow an autosomal recessive pattern on inheritance. Many cases are reported in children from consanguineous unions. Genetic counseling should be proposed to individuals having the disease-causing mutation informing them that there is 25% risk of passing the mutation to offspring.Management and treatmentThere is no specific treatment for MONA spectrum. Management is primarily symptomatic. Some patients initially respond to non-steroidal anti-inflammatory drugs (NSAIDs).PrognosisThe progressive joint destruction leads to significant disability; many patients are wheelchair bound. However, life expectancy does not appear to be significantly affected.Visit the Orphanet disease page for more resources.
MalaCards based summary :
Multicentric Osteolysis, Nodulosis, and Arthropathy, also known as
torg-winchester syndrome, is related to
multicentric osteolysis-nodulosis-arthropathy spectrum and
winchester syndrome. An important gene associated with Multicentric Osteolysis, Nodulosis, and Arthropathy is
MMP2 (Matrix Metallopeptidase 2). The drugs
Copper and
Copper Supplement have been mentioned in the context of this disorder. Affiliated tissues include
bone,
eye and
skin, and related phenotypes are
coarse facial features and
corneal opacity
MedlinePlus Genetics :
43
Multicentric osteolysis, nodulosis, and arthropathy (MONA) describes a rare inherited disease characterized by a loss of bone tissue (osteolysis), particularly in the hands and feet. MONA includes a condition formerly called nodulosis-arthropathy-osteolysis (NAO) syndrome. It may also include a similar disorder called Torg syndrome, although it is unknown whether Torg syndrome is actually part of MONA or a separate disorder caused by a mutation in a different gene.In most cases of MONA, bone loss begins in the hands and feet, causing pain and limiting movement. Bone abnormalities can later spread to other areas of the body, with joint problems (arthropathy) occurring in the elbows, shoulders, knees, hips, and spine. Most people with MONA 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.Many affected individuals develop subcutaneous nodules, which are firm lumps of noncancerous tissue underneath the skin, especially on the soles of the feet. Some affected individuals also have skin abnormalities including patches of dark, thick, and leathery skin. Other features of MONA 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."
OMIM® :
57
Zankl et al. (2007) defined what they considered to be a continuous clinical spectrum involving Torg syndrome, Winchester syndrome (277950), and NAO syndrome. Torg syndrome is characterized by the presence of multiple, painless, subcutaneous nodules and mild to moderate osteoporosis and osteolysis that is usually limited to the hands and feet. Radiographically, the osteolysis is accompanied by a characteristic widening of the metacarpal and metatarsal bones. Winchester syndrome presents with severe osteolysis in the hands and feet and generalized osteoporosis and bone thinning, similar to NAO, but subcutaneous nodules are characteristically absent. Various additional features including coarse face, corneal opacities, gum hypertrophy, and EKG changes have been reported. NAO syndrome, which has only been described in patients from Saudi Arabia, is generally more severe, with multiple prominent and painful subcutaneous nodules, massive osteolysis in the hands and feet, and generalized osteoporosis. Coarse face and body hirsutism are additional features.
(259600) (Updated 05-Mar-2021)
KEGG :
36
Torg syndrome, also known as Multicentric osteolysis, nodulosis, and arthropathy (MONA) is a multicentric osteolysis syndrome characterized by progressive bone loss in hands and feet. MMP2 mutations are reported in patients with Torg-Winchester syndrome.
UniProtKB/Swiss-Prot :
73
Multicentric osteolysis, nodulosis, and arthropathy: An autosomal recessive syndrome characterized by severe multicentric osteolysis with predominant involvement of the hands and feet. Additional features include coarse face, corneal opacities, patches of thickened, hyperpigmented skin, hypertrichosis and gum hypertrophy.
