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Multicentric osteolysis nodulosis arthropathy spectrum(MONA)

MedGen UID:
342428
Concept ID:
C1850155
Disease or Syndrome
Synonyms: Osteolysis, hereditary multicentric; Winchester-Grossman syndrome
SNOMED CT: Multicentric osteolysis nodulosis arthropathy spectrum (716868003); MONA (multicentric osteolysis nodulosis arthropathy) spectrum (716868003)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Related genes: MMP14, MMP2
 
Monarch Initiative: MONDO:0018298
OMIM®: 120360; 259600
Orphanet: ORPHA371428

Disease characteristics

Multicentric osteolysis nodulosis and arthropathy (MONA) is a skeletal dysplasia characterized by progressive osteolysis (particularly of the carpal and tarsal bones), osteoporosis, subcutaneous nodules on the palms and soles, and progressive arthropathy (joint contractures, pain, swelling, and stiffness). Other manifestations include coarse facies, pigmented skin lesions, cardiac defects, and corneal opacities. Onset is usually between ages six months and six years (range: birth to 11 years). [from GeneReviews]
Authors:
Gandham SriLakshmi Bhavani  |  Hitesh Shah  |  Anju Shukla, et. al.   view full author information

Additional descriptions

From OMIM
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.  http://www.omim.org/entry/259600
From MedlinePlus Genetics
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."  https://medlineplus.gov/genetics/condition/multicentric-osteolysis-nodulosis-and-arthropathy

Clinical features

From HPO
Arthralgia
MedGen UID:
13917
Concept ID:
C0003862
Sign or Symptom
Joint pain.
Pes planus
MedGen UID:
42034
Concept ID:
C0016202
Anatomical Abnormality
A foot where the longitudinal arch of the foot is in contact with the ground or floor when the individual is standing; or, in a patient lying supine, a foot where the arch is in contact with the surface of a flat board pressed against the sole of the foot by the examiner with a pressure similar to that expected from weight bearing; or, the height of the arch is reduced.
Finger swelling
MedGen UID:
65989
Concept ID:
C0239598
Finding
Enlargement of the soft tissues of one or more fingers.
Protrusio acetabuli
MedGen UID:
98369
Concept ID:
C0409495
Anatomical Abnormality
Intrapelvic bulging of the medial acetabular wall.
Pes cavus
MedGen UID:
675590
Concept ID:
C0728829
Congenital Abnormality
An increase in height of the medial longitudinal arch of the foot that does not flatten on weight bearing (i.e., a distinctly hollow form of the sole of the foot when it is bearing weight).
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.
Ankle flexion contracture
MedGen UID:
332440
Concept ID:
C1837407
Anatomical Abnormality
Broad metacarpals
MedGen UID:
330796
Concept ID:
C1842229
Finding
Abnormally broad metacarpal bones.
Broad metatarsal
MedGen UID:
330797
Concept ID:
C1842231
Finding
Increased side-to-side width of a metatarsal bone.
Interphalangeal joint erosions
MedGen UID:
340477
Concept ID:
C1850158
Finding
Widened metacarpal shaft
MedGen UID:
340478
Concept ID:
C1850159
Finding
Thin metacarpal cortices
MedGen UID:
376718
Concept ID:
C1850160
Finding
Thin metatarsal cortices
MedGen UID:
342430
Concept ID:
C1850162
Finding
Metacarpal osteolysis
MedGen UID:
343165
Concept ID:
C1854610
Finding
Metatarsal osteolysis
MedGen UID:
344327
Concept ID:
C1854614
Finding
Osteolysis involving metatarsal bones.
Split hand
MedGen UID:
397570
Concept ID:
C2699510
Congenital Abnormality
A condition in which middle parts of the hand (fingers and metacarpals) are missing giving a cleft appearance. The severity is very variable ranging from slightly hypoplastic middle fingers over absent middel fingers as far as oligo- or monodactyl hands.
Distal tapering of metatarsals
MedGen UID:
870287
Concept ID:
C4024729
Anatomical Abnormality
Mitral valve prolapse
MedGen UID:
7671
Concept ID:
C0026267
Disease or Syndrome
One or both of the leaflets (cusps) of the mitral valve bulges back into the left atrium upon contraction of the left ventricle.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk. In general, this can refer to neurological diseases but also fractures or other sources of pain that is triggered upon walking. However, in the current context gait disturbance refers to difficulty walking on the basis of a neurological or muscular disease.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Osteopenia
MedGen UID:
18222
Concept ID:
C0029453
Disease or Syndrome
Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5.
Osteoporosis
MedGen UID:
14535
Concept ID:
C0029456
Disease or Syndrome
Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD).
Frontal bossing
MedGen UID:
67453
Concept ID:
C0221354
Congenital Abnormality
Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.
Brachycephaly
MedGen UID:
113165
Concept ID:
C0221356
Congenital Abnormality
An abnormality of skull shape characterized by a decreased anterior-posterior diameter. That is, a cephalic index greater than 81%. Alternatively, an apparently shortened anteroposterior dimension (length) of the head compared to width.
Hypoplasia of the maxilla
MedGen UID:
66804
Concept ID:
C0240310
Congenital Abnormality
Abnormally small dimension of the Maxilla. Usually creating a malocclusion or malalignment between the upper and lower teeth or resulting in a deficient amount of projection of the base of the nose and lower midface region.
Vertebral compression fracture
MedGen UID:
75497
Concept ID:
C0262431
Finding
Wrist flexion contracture
MedGen UID:
592338
Concept ID:
C0409345
Acquired Abnormality
A chronic loss of wrist joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevent normal movement of the joints of the wrist.
Hip contracture
MedGen UID:
140815
Concept ID:
C0409354
Acquired Abnormality
Lack of full passive range of motion (restrictions in flexion, extension, or other movements) of the hip joint resulting from structural changes of non-bony tissues, such as muscles, tendons, ligaments, joint capsules and/or skin.
Wide cranial sutures
MedGen UID:
140825
Concept ID:
C0410935
Finding
An abnormally increased width of the cranial sutures for age-related norms (generally resulting from delayed closure).
Kyphoscoliosis
MedGen UID:
154361
Concept ID:
C0575158
Anatomical Abnormality
An abnormal curvature of the spine in both a coronal (lateral) and sagittal (back-to-front) plane.
Thin bony cortex
MedGen UID:
318844
Concept ID:
C1833325
Finding
Abnormal thinning of the cortical region of bones.
C1-C2 subluxation
MedGen UID:
376359
Concept ID:
C1848446
Finding
A partial dislocation of the atlantoaxial joints.
Metaphyseal widening
MedGen UID:
341364
Concept ID:
C1849039
Finding
Abnormal widening of the metaphyseal regions of long bones.
Delayed closure of the anterior fontanelle
MedGen UID:
825928
Concept ID:
C3840083
Finding
A delay in closure (ossification) of the anterior fontanelle, which generally undergoes closure around the 18th month of life.
Camptodactyly of toe
MedGen UID:
867404
Concept ID:
C4021774
Anatomical Abnormality
Camptodactyly is a painless flexion contracture of the proximal interphalangeal (PIP) joint that is usually gradually progressive. This term refers to camptodactyly of one or more toes.
Interphalangeal joint contracture of finger
MedGen UID:
867413
Concept ID:
C4021784
Anatomical Abnormality
Chronic loss of joint motion in an interphalangeal joint of a finger due to structural changes in non-bony tissue.
Ankylosis of feet small joints
MedGen UID:
870290
Concept ID:
C4024732
Disease or Syndrome
Sclerotic cranial sutures
MedGen UID:
870740
Concept ID:
C4025195
Finding
An increased density in the cranial sutures following obliteration.
Antinuclear antibody positivity
MedGen UID:
101792
Concept ID:
C0151480
Laboratory or Test Result
The presence of autoantibodies in the serum that react against nuclei or nuclear components.
Delayed eruption of teeth
MedGen UID:
68678
Concept ID:
C0239174
Finding
Delayed tooth eruption, which can be defined as tooth eruption more than 2 SD beyond the mean eruption age.
Bulbous nose
MedGen UID:
66013
Concept ID:
C0240543
Finding
Increased volume and globular shape of the anteroinferior aspect of the nose.
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.
Narrow nasal bridge
MedGen UID:
1641596
Concept ID:
C4551564
Finding
Decreased width of the bony bridge of the nose.
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.
Thickened skin
MedGen UID:
66024
Concept ID:
C0241165
Finding
Laminar thickening of skin.
Hypermelanotic macule
MedGen UID:
375013
Concept ID:
C1842774
Finding
A hyperpigmented circumscribed area of change in normal skin color without elevation or depression of any size.
Corneal opacity
MedGen UID:
40485
Concept ID:
C0010038
Finding
A reduction of corneal clarity.
Proptosis
MedGen UID:
41917
Concept ID:
C0015300
Disease or Syndrome
An eye that is protruding anterior to the plane of the face to a greater extent than is typical.
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).
Peripheral opacification of the cornea
MedGen UID:
509788
Concept ID:
C0155100
Finding
Reduced transparency of the peripheral region of the cornea.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Multicentric osteolysis nodulosis arthropathy spectrum in Orphanet.

Recent clinical studies

Etiology

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
Zankl A, Bonafé L, Calcaterra V, Di Rocco M, Superti-Furga A
Clin Genet 2005 Mar;67(3):261-6. doi: 10.1111/j.1399-0004.2004.00402.x. PMID: 15691365

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
Zankl A, Bonafé L, Calcaterra V, Di Rocco M, Superti-Furga A
Clin Genet 2005 Mar;67(3):261-6. doi: 10.1111/j.1399-0004.2004.00402.x. PMID: 15691365

Prognosis

Ishaq T, Loid P, Ishaq HA, Seo GH, Mäkitie O, Naz S
BMC Musculoskelet Disord 2023 Sep 14;24(1):735. doi: 10.1186/s12891-023-06856-2. PMID: 37710205Free PMC Article

Clinical prediction guides

Ishaq T, Loid P, Ishaq HA, Seo GH, Mäkitie O, Naz S
BMC Musculoskelet Disord 2023 Sep 14;24(1):735. doi: 10.1186/s12891-023-06856-2. PMID: 37710205Free PMC Article
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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