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Disease Profile

Multicentric osteolysis, nodulosis and arthropathy

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

#N/A

ICD-10

#N/A

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Torg-Winchester Syndrome; Torg Syndrome; Nodulosis-Arthropathy-Osteolysis Syndrome,;

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 371428

Definition
A 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.

Epidemiology
Multicentric 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 description
Onset 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).

Etiology
MONA 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 methods
The diagnosis is based on the clinical manifestations of the disease and can be confirmed by molecular genetic testing.

Differential diagnosis
The main differential diagnoses are juvenile idiopathic arthritis and multicentric carpotarsal osteolysis.

Genetic counseling
MONA 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 treatment
There is no specific treatment for MONA spectrum. Management is primarily symptomatic. Some patients initially respond to non-steroidal anti-inflammatory drugs (NSAIDs).

Prognosis
The 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.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal facial shape
Unusual facial appearance
0001999
Abnormal hand morphology
Abnormal shape of hand
0005922
Arthritis
Joint inflammation
0001369
Arthropathy
Disease of the joints
0003040
Carpal osteolysis
0001495
Hirsutism
Excessive hairiness
0001007
Osteolysis involving tarsal bones
0006234
Osteopenia
0000938
Osteoporosis
0000939
30%-79% of people have these symptoms
Abnormal form of the vertebral bodies
0003312
Brachycephaly
Short and broad skull
0000248
Broad clavicles
Broad collarbone
0000916
Broad metacarpals
Wide long bones of hand
0001230
Sclerotic cranial sutures
0005441
Subcutaneous nodule
Growth of abnormal tissue under the skin
Firm lump under the skin

[ more ]

0001482
5%-29% of people have these symptoms
Abnormality of the orbital region
Abnormality of the eye region
Abnormality of the region around the eyes

[ more ]

0000315
Atrial septal defect
An opening in the wall separating the top two chambers of the heart
Hole in heart wall separating two upper heart chambers

[ more ]

0001631
Atrioventricular block
Interruption of electrical communication between upper and lower chambers of heart
0001678
Bicuspid aortic valve
Aortic valve has two leaflets rather than three
0001647
Coarctation of aorta
Narrowing of aorta
Narrowing of the aorta

[ more ]

0001680
Double outlet right ventricle
0001719
Hypertension
0000822
Increased susceptibility to fractures
Abnormal susceptibility to fractures
Bone fragility
Frequent broken bones
Increased bone fragility
Increased tendency to fractures

[ more ]

0002659
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Iris coloboma
Cat eye
0000612
Mitral valve prolapse
0001634
Nodular goiter
0005994
Omphalocele
0001539
Papilledema
0001085
Polycystic ovaries
0000147
Premature thelarche
Premature breast development
0010314
Pterygium
0001059
Type I diabetes mellitus
Type 1 diabetes
Type I diabetes

[ more ]

0100651
Ventricular septal defect
Hole in heart wall separating two lower heart chambers
0001629
1%-4% of people have these symptoms
Bulbous nose
0000414
C1-C2 subluxation
0003320
Childhood onset
Symptoms begin in childhood
0011463
Coarse facial features
Coarse facial appearance
0000280
Corneal opacity
0007957
Gingival overgrowth
Gum enlargement
0000212
Infantile onset
Onset in first year of life
Onset in infancy

[ more ]

0003593
Kyphoscoliosis
0002751
Wide cranial sutures
Large cranial suture
Persistent open cranial sutures

[ more ]

0010537
Percent of people who have these symptoms is not available through HPO
Ankle flexion contracture
0006466
Ankylosis of feet small joints
0008090
Antinuclear antibody positivity
0003493
Arthralgia
Joint pain
0002829
Autosomal recessive inheritance
0000007
Broad metatarsal
Wide long bone of foot
0001783
Camptodactyly of toe
0001836
Delayed closure of the anterior fontanelle
Later than typical closing of soft spot of skull
0001476
Delayed eruption of teeth
Delayed eruption
Delayed teeth eruption
Delayed tooth eruption
Eruption, delayed
Late eruption of teeth
Late tooth eruption

[ more ]

0000684
Distal tapering of metatarsals
0008133
Finger swelling
0025131
Frontal bossing
0002007
Gait disturbance
Abnormal gait
Abnormal walk
Impaired gait

[ more ]

0001288
Hip contracture
0003273
Hypermelanotic macule
Hyperpigmented spots
0001034
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Hypoplasia of the maxilla
Decreased size of maxilla
Decreased size of upper jaw
Maxillary deficiency
Maxillary retrusion
Small maxilla
Small upper jaw
Small upper jaw bones
Upper jaw deficiency
Upper jaw retrusion

[ more ]

0000327
Interphalangeal joint contracture of finger
0001220

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Multicentric osteolysis, nodulosis and arthropathy. This website is maintained by the National Library of Medicine.

    In-Depth Information

    • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
    • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
    • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.

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