scapuloperoneal spinal muscular atrophy, autosomal dominant

Scapuloperoneal spinal muscular atrophy, autosomal dominant is a neuromuscular condition that primarily affects the muscles of the shoulder and lower leg regions. It is associated with variants in the TRPV4 gene, which play a role in cellular signaling and muscle function. This condition is very rare, affecting fewer than one person per million. Although its onset and progression can vary, affected individuals typically experience muscle weakness and other neuromuscular symptoms to differing degrees.

The clinical presentation of this condition can be quite variable. Affected individuals may experience distal sensory impairment, noted in approximately 5 to 29% of cases, along with neuromuscular weakness that affects movement in the shoulder and leg areas. Not all individuals experience all features, and severity can vary considerably from one person to another. Because symptoms overlap with other neuromuscular disorders, careful clinical evaluation is essential.

This condition results from pathogenic variants in the TRPV4 gene. In an autosomal dominant inheritance pattern, a single altered copy of TRPV4 is sufficient to increase the risk of developing the condition. It is important to understand that even within the same family, not every individual who inherits the TRPV4 variant will necessarily develop symptoms, and the severity and types of symptoms can vary widely (variable expressivity). Families are encouraged to seek genetic counseling to better understand individual risks and implications for family planning.

Management of this condition involves targeted therapies as there are no established foundational therapies for symptom support specific to this disorder. Currently, FDA-approved treatments include SPINRAZA (nusinersen) and EVRYSDI (risdiplam). In addition, FDA-approved gene therapy such as Zolgensma (onasemnogene abeparvovec-xioi), which is regulated by the FDA’s Center for Biologics Evaluation and Research (CBER), represents another therapeutic approach. Patients should work closely with their healthcare team to determine the most appropriate treatment options, and genetic counseling is recommended to support informed decision-making.

Outcomes in scapuloperoneal spinal muscular atrophy, autosomal dominant can vary widely between individuals. Some may experience relatively stable symptoms over time, while others might see a progression in muscle weakness or other neuromuscular challenges. With current standards of care and the availability of modern therapeutic options, overall quality of life has improved, though individual experiences differ significantly. Outcomes described in medical literature continue to evolve as standards of care improve, and connecting with a genetic counselor or specialist can provide valuable guidance for long-term management.