Multicentric Osteolysis Nodulosis and Arthropathy

Clinical 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).

Diagnosis/testing: The diagnosis of MONA is established in a proband with characteristic clinical and radiographic findings and either biallelic pathogenic variants in MMP2 or decreased activity of the enzyme matrix metalloproteinase 2.

Management: Treatment of manifestations: Treatment is supportive only and can include physical therapy (which may slow the rate of development of contractures and prolong mobility) and mobility aids. Pain medications may not provide relief unless the pain is due to secondary osteoarthritis/contractures. Daily recommended supplementation of vitamin D and calcium; standard management of congenital heart defects; management of scoliosis and kyphosis per orthopedist.

Surveillance: Annual joint assessment by a rheumatologist or orthopedic surgeon. Evaluation with cardiologist as needed for follow up of congenital heart disease. Annual assessment for scoliosis and kyphosis.

Agents/circumstances to avoid: Physical trauma to reduce the risk of fractures.

Genetic counseling: MONA is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the MMP2 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal and preimplantation genetic testing for a pregnancy at increased risk are possible.