Torg-Winchester syndrome

Torg-Winchester syndrome

Torg-Winchester syndrome (MIM 259600) is an autosomal recessive disorder. It was originally defined as three separate entities: Torg syndrome, Winchester syndrome and multicentric osteolysis with nodulosis and arthropathy (NOA syndrome). The 2006 revision of the Nosology of Constitutional Disorders of Bone classified Torg and Winchester syndromes as a single entity with NOA syndrome as a variant. Torg syndrome is characterized by a mild to moderate osteoporosis and osteolysis that is usually limited to the hands and feet. Widening of the metacarpal and metatarsal shafts, narrowing of the joints and erosions are seen. Contractures and progression involvement of other joints may occur. Another feature of Torg- syndrome is the presence of painless subcutaneous nodules. In Winchester syndrome there is severe osteolysis in the hands and feet and generalized osteoporosis. These patients do not have subcutaneous nodules. Facial dysmorphism, corneal opacities gum hypertrophy and EKG changes may be features. NOA syndrome patients display features of both Torg syndrome and Winchester syndrome. There is massive carpal and tarsal osteolysis, interphalangeal joint erosions with flexion contractures, generalized osteoporosis, facial dysmorphism, body hirsutism, and multiple painful plantar and palmar subcutaneous nodules. Torg-Winchester syndrome and NOA syndrome are caused by loss of function mutations in the matrix metalloproteinase 2 gene (MMP2). This gene encodes type IV collagenase also known as gelatinase A.