Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2021 Jul 10:15:101106.
doi: 10.1016/j.bonr.2021.101106. eCollection 2021 Dec.

Multicentric Osteolysis, Nodulosis, and Arthropathy in two unrelated children with matrix metalloproteinase 2 variants: Genetic-skeletal correlations

Affiliations
Case Reports

Multicentric Osteolysis, Nodulosis, and Arthropathy in two unrelated children with matrix metalloproteinase 2 variants: Genetic-skeletal correlations

Hanan Elsebaie et al. Bone Rep. .

Abstract

Multicentric Osteolysis, Nodulosis, and Arthropathy (MONA) syndrome is a rare genetic skeletal dysplasia. Its diagnosis can be deceptively similar to childhood-onset genetic skeletal dysplasias and juvenile idiopathic arthritis. We aimed to report the syndrome's clinical and radiologic features with emphasis on skeletal manifestations. And establish relevant phenotype-genotype correlations. We evaluated two boys, 4-and-7-years-old with MONA syndrome. Both patients had consanguineous parents. We verified the diagnosis by correlating the outcomes of clinical, radiologic and molecular analysis. We specifically evaluated the craniofacial morphology and clinical and radiographic skeletal abnormalities. We contextualized the resultant phenotype-genotype correlations to publications on MONA and its differential diagnosis. Skeletal manifestations were the presenting symptoms and mostly restricted to hands and feet in terms of fixed extension deformity of the metacarpophalangeal and flexion deformity of the interphalangeal joints with extension deformity of big toes. There were arthritic symptoms in the older patient especially of the wrists and minute pathologic fractures. The skeletal radiographs showed osteopenia/dysplastic changes of hands and feet. Both patients had variants in the matrix metalloproteinase2 gene which conformed to phenotype of previously reported literature in one patient while the other had a novel variant which conformed to MONA phenotype. Craniofacial abnormalities were present. However, minimal extra-skeletal manifestations. Overall, there is an emerging distinctive skeletal pattern of involvement in terms of both clinical and radiographic features. This includes age of onset and location of presenting skeletal manifestations, chronological order of joint affection, longitudinal disease progression, specifics of skeletal radiographic pathology and craniofacial features. Nevertheless, physicians are cautioned against differential diagnosis of similar genetic skeletal dysplasias and juvenile idiopathic arthritis.

Keywords: Childhood osteoporosis; Frank-Ter Haar syndrome; Juvenile idiopathic arthritis; MMP2 gene mutations; MONA syndrome; Torg-Winchester syndrome.

PubMed Disclaimer

Conflict of interest statement

Nothing to declare.

Figures

Unlabelled Image
Graphical abstract
Fig. 1
Fig. 1
(a, b): Patient 1. Right hand. Note the claw hand attitude created by fixed extension deformity of metacarpophalangeal joints and flexion of the interphalangeal joints of lesser fingers. Note the scars of previous soft tissue releases. Realize the thumb is spared.
Fig. 2
Fig. 2
(a, b, c): Patient 1. Radioclinical presentation of hands and feet. (a) Right hand shows extension and flexion deformity of the metacarpophalangeal and proximal interphalangeal joints respectively. Left hand shows a similar deformity but restricted to the little finger. (b) Radiographs show diffuse osteopenia, bilateral carpal osteolysis more pronounced on the right (hollow arrows) with minute pathologic fractures of metacarpals and feet (not shown). Note tapering of the proximal ends of some metacarpals. Note the transverse metaphyseal striations (arrows) which indicate previous bisphosphonate therapy. (c) Note the diffuse osteopenia of both feet and the osteolysis of the midtarsal joints especially of the right foot which also shows a hallux valgus deformity.
Fig. 3
Fig. 3
Patient 2. Craniofacial features. Dysmorphism in the form of triangular face with frontal bossing, heavy thick eye brows with partial synophyrus, depressed nasal bridge, bilateral asymmetric ptosis with down-slanting palpebral fissures and strabismus, hypertelorism, thick protruding lower lip, low set posteriorly rotated bat ears and a relatively thin chin.
Fig. 4
Fig. 4
(a, b, c, d): Patient 2. Clinical presentations of both hands. (a, b) Volar view. Note the claw hand attitude created by fixed extension deformity of metacarpophalangeal joints and flexion of the interphalangeal joints of the 4th and 5th fingers. (c, d) Dorsal view. Note the same clawing features seen in the previous figures.
Fig. 5
Fig. 5
Patient 2. Radiographic presentation of hands. Radiographs of both hands show widespread osteopenia (cortical thinning and hypodensity), coarse trabecular pattern, tapering of the proximal ends of the metacarpals (arrows) and confirm the clinical deformity.
Fig. 6
Fig. 6
(a, b, c): Patient 2. Radioclinical presentation of feet. (a) Note the undersized left foot, convexity of the sole i.e. loss of arch concavity (rocker bottom deformity) and clawing of big toe i.e. extension of metacarpophalangeal joint and flexion of the interphalangeal. (b) Note the diffuse osteopenia, cortical irregularities, disappearance of head of talus and dysplastic changes of left hindfoot with a vertical talus deformity (demarcation lines). The right foot is unremarkable. (c) Left foot. Note the loss of normal concavity of the foot arch and even emergence of a sole convexity. Mark the clawing of big toe in the form of extension deformity at the first metacarpophalangeal joint and flexion deformity at the interphalangeal the joint.
Fig. 7
Fig. 7
Patient 2. Close-up lateral view of Lumber 1 and lower dorsal vertebrae. Note the mild anterior notching or scalloping of the anterior bodies (arrows).
Fig. 8
Fig. 8
Family pedigree of patient 2.

Similar articles

Cited by

References

    1. Al Aqeel A., Al Sewairi W., Edress B., Gorlin R.J., Desnick R.J., Martignetti J.A. Inherited multicentric osteolysis with arthritis: a variant resembling Torg syndrome in a Saudi family. Am. J. Med. Genet. 2000;93:11–18. doi: 10.1002/1096-8628(20000703)93:1<11::AID-AJMG3>3.0.CO;2-3. - DOI - PubMed
    1. Al Kaissi A., Scholl-Buergi S., Biedermann R., Maurer K., Hofstaetter J.G., Klaushofer K. The diagnosis and management of patients with idiopathic osteolysis. Pediatr. Rheumatol. Online J. 2011;9:31. doi: 10.1186/1546-0096-9-31. - DOI - PMC - PubMed
    1. Al Kaissi A., Kenis V., Jemaa L.B., Sassi H., Shboul M., Grill F. Skeletal phenotype/genotype in progressive pseudorheumatoid chondrodysplasia. Clin. Rheumatol. 2020;39:553–560. doi: 10.1007/s10067-019-04783-z. - DOI - PubMed
    1. Allanson J.E., Cunniff C., Hoyme H.E., McGaughran J., Muenke M., Neri G. Elements morphology: standard of terminology for the head and face. Am. J. Med. Genet. A. 2009;149A:6–28. doi: 10.1002/ajmg.a.32612. - DOI - PMC - PubMed
    1. Al-Mayouf S.M., Majeed M., Hugosson C., Bahabri S. New form of idiopathic osteolysis: nodulosis, arthropathy and osteolysis (NAO) syndrome. Am. J. Med. Genet. 2000;93:5–10. doi: 10.1002/1096-8628(20000703)93:1<5::AID-AJMG2>3.0.CO;2-Y. - DOI - PubMed

Publication types

LinkOut - more resources