Clinical and mutation profile of multicentric osteolysis nodulosis and arthropathy

Abstract

Multicentric osteolysis nodulosis and arthropathy (MONA) is an infrequently described autosomal recessive skeletal dysplasia characterized by progressive osteolysis and arthropathy. Inactivating mutations in MMP2, encoding matrix metalloproteinase-2, are known to cause this disorder. Fifteen families with mutations in MMP2 have been reported in literature. In this study we screened thirteen individuals from eleven families for MMP2 mutations and identified eight mutations (five novel and three known variants). We characterize the clinical, radiographic and molecular findings in all individuals with molecularly proven MONA from the present cohort and previous reports, and provide a comprehensive review of the MMP2 related disorders.

Multicentric osteolytic syndromes represent a phenotypic spectrum defined by defective collagen remodeling

“…In doing so, MMP2 directly cooperates with MMP14 and augments its collagenolytic activity (Ohuchi et al, ; Sato et al, ; Takino et al, ). The relevance of MMP2 activity is reflected by the overlap between the MMP14 and MMP2‐related human phenotypes, as outlined above (Al Aqeel et al, ; Al Kaissi et al, ; Azzollini et al, ; Bader‐Meunier et al, ; Bhavani et al, ; Castberg et al, ; De Vos et al, ; Eisenstein et al, ; Ekbote et al, ; Gok et al, ; Jeong et al, ; Martignetti et al, ; Phadke & Dalal, ; Pichler et al, ; Rouzier et al, ; Temtamy et al, ; Tuysuz et al, ; Vanatka et al, ; Zankl et al, , ).…”

“…Most examined individuals with an SH3PXD2B or MMP14 mutation had a broad mouth, as well as one third of examined patients with an MMP2 mutation. Finally, thick lips and either a small or heavy mandible have been reported in most examined patients with an SH3PXD2B , MMP14 , or MMP2 mutation (Al Aqeel et al, ; Al Kaissi et al, ; Azzollini et al, ; Bader‐Meunier et al, ; Bendon et al, ; Bhavani et al, ; Borrone et al, ; Castberg et al, ; Chang et al, ; Eisenstein et al, ; Ekbote et al, ; Gok et al, ; Hamel et al, ; Iqbal et al, ; Jeong et al, ; Maas et al, ; Martignetti et al, ; Mégarbané et al, ; Phadke & Dalal, ; Pichler et al, ; Prapanpoch et al, ; Rouzier et al, ; Temtamy et al, ; Ter Haar et al, ; Tuysuz et al, ; Vanatka et al, ; Van Steensel et al, ; Wilson et al, ; Winchester et al, ; Zankl et al, ; Zankl et al, ; Zrhidri et al, ).…”

“…Gingival hypertrophy has been reported in ≥50% of examined individuals with an SH3PXD2B , MMP14 , or MMP2 mutation (Table ). Delayed dentition, attributed to gingival hypertrophy, was less frequently reported (Al Aqeel et al, ; Bader‐Meunier et al, ; Bhavani et al, ; Borrone et al, ; Chang et al, ; Eisenstein et al, ; Ekbote et al, ; Martignetti et al, ; Mégarbané et al, ; Phadke & Dalal, ; Prapanpoch et al, ; Temtamy et al, ; Tuysuz et al, ; Van Steensel et al, ; Wilson et al, ; Winchester et al, ; Zankl et al, ).…”

“…Ventricle septum defect and outflow tract anomalies have additionally been documented in patients with an SH3PXD2B mutation and are less frequent in individuals with an MMP2 mutation. These cardiac anomalies caused early childhood death of multiple patients (Al Kaissi et al, ; Azzollini et al, ; Bendon et al, ; Bhavani et al, ; Borrone et al, ; Castberg et al, ; Chang et al, ; Ekbote et al, ; Gok et al, ; Hamel et al, ; Iqbal et al, ; Maas et al, ; Mégarbané et al, ; Pichler et al, ; Temtamy et al, ; Ter Haar et al, ; Tuysuz et al, ; Van Steensel et al, ; Wilson et al, ; Zrhidri et al, ).…”

Gorham-Stout Disease: Case Report and Suggested Diagnostic Evaluation of a Rare Clinical Entity

“…These include infection, cancer, inflammatory, endocrine disorders, and other osteolysis syndromes (1). In our patient, the diagnosis of GSD was based on the exclusion of other syndromes as he did not fit other osteolysis syndromes such as Hajdu Cheney or Winchester syndrome (he was of a normal height with no characteristic distal osteolysis at the hands and feet or facial features), or multicentric carpotarsal osteolysis syndrome (he had no renal failure or distal osteolysis) (11)(12)(13). Given that his affected area was localized to the axial skeleton without any other clinical symptoms, a genetic syndrome was unlikely.…”