Vanishing Bones and Stubborn Joints: Unravelling the Enigma of Multicentric Osteolysis, Nodulosis, and Arthropathy Syndrome

TL;DR

This paper presents two cases of MONA syndrome, a rare genetic bone disorder, and highlights the importance of genetic testing for accurate diagnosis.

Contribution

The study contributes two new case reports with confirmed MMP2 mutations and emphasizes the role of genetic testing in diagnosing MONA syndrome.

Findings

Two patients with MONA syndrome were found to have homozygous MMP2 mutations confirmed via genetic testing.

X-rays revealed bone lysis in carpal, metacarpal, tarsal, and metatarsal bones in the patients.

Early suspicion of MONA syndrome is critical to avoid misdiagnosis and inappropriate treatment.

Abstract

Multicentric osteolysis, nodulosis, and arthropathy (MONA) syndrome is a rare inherited skeletal disorder, transmitted in an autosomal recessive manner, marked by gradual bone loss, especially affecting the carpal and tarsal bones, and the presence of subcutaneous nodules. The condition results from mutations in the MMP2 gene, which encodes matrix metalloproteinase-2, an enzyme essential for extracellular matrix remodeling. MONA typically begins in early childhood and can resemble juvenile idiopathic arthritis, often leading to delayed or incorrect diagnosis.

We describe the case of two patients with progressive, noninflammatory joint deformities and characteristic palmoplantar nodules with coarse facies. Routine investigations were normal; X-rays of the affected joints showed lysis of multiple carpal, metacarpal, tarsal, and metatarsal bones. Therefore, whole exome sequencing was performed for diagnosis. We analyzed pertinent literature outlining the diverse clinical manifestations of MONA syndrome and emphasizing the pivotal importance of genetic testing in its diagnosis and management. Genetic testing revealed homozygous MMP2 mutations, c.301C>T (p.Arg101Cys) and c.556G>C (p.Gly186Arg), confirming the diagnosis of MONA syndrome. Our literature review included 12 relevant articles outlining clinical features and associated genetic mutations. Early suspicion of MONA is crucial to prevent inappropriate use of immunosuppressants and to facilitate timely genetic confirmation. Given the condition’s rarity and clinical overlap with other disorders, case reports are the key to advancing diagnosis and further supportive management.

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