Multicentric osteolysis-nodulosis-arthropathy spectrum (ORPHA:371428)
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.

                            Last update: 
                            November 2019


                            - Expert reviewer(s): 
                            Dr Andreas ZANKL