Multiple synostoses syndrome

Multiple synostoses syndrome (SYNS) is a rare genetic skeletal disorder characterized by progressive joint fusions (synostoses) affecting multiple joints throughout the body. The condition primarily impacts the skeletal system, with fusion occurring in the joints of the fingers (symphalangism), wrists, elbows, ankles, and vertebrae. Affected individuals typically present with stiffness and reduced range of motion in multiple joints, which worsens over time as bony fusions progress. Additional features may include conductive hearing loss due to fusion of the ossicles (small bones of the middle ear), a broad and short nose with a flattened nasal bridge, and characteristic facial features. The condition is sometimes referred to as symphalangism with multiple other joint fusions or SYNS. Multiple synostoses syndrome is caused by heterozygous mutations in genes involved in bone morphogenetic protein (BMP) signaling, including NOG (encoding noggin, SYNS1), GDF5 (SYNS2), and GDF6 (SYNS3). These genes play critical roles in joint formation and skeletal development during embryogenesis. The condition shows significant clinical overlap with other disorders of the symphalangism spectrum, including proximal symphalangism and tarsal-carpal coalition syndrome, which are now understood to represent a phenotypic continuum. There is currently no cure for multiple synostoses syndrome. Treatment is supportive and symptomatic, focusing on maintaining joint function through physical therapy and occupational therapy. Hearing aids may be beneficial for individuals with conductive hearing loss. Surgical interventions may be considered in select cases to improve function, though outcomes can be limited by the progressive nature of the joint fusions. Genetic counseling is recommended for affected families given the autosomal dominant inheritance pattern.

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