autosomal dominant childhood-onset proximal spinal muscular atrophy without contractures

Autosomal dominant childhood-onset proximal spinal muscular atrophy without contractures is a neuromuscular condition that primarily affects muscle strength in the proximal regions, especially in the lower extremities. The disorder is caused by alterations in the DYNC1H1 gene, which plays a crucial role in intracellular transport and neuronal function. It typically manifests in childhood and is very rare, affecting fewer than 1 in 1 million people. Due to its rarity and variable clinical presentation, ongoing advancements in care continue to shape outcomes for affected individuals.

The clinical presentation of this condition is variable, with many individuals experiencing global developmental delay that may influence cognitive and neurological functioning. Although specific characteristic findings are not well defined, affected children may show signs of motor difficulties alongside developmental challenges. Not all individuals experience all features, and severity varies considerably, emphasizing the importance of individualized assessment and management.

The condition is linked to pathogenic variants in the DYNC1H1 gene, which encodes a protein integral to the dynein motor complex responsible for intracellular transport and neuronal maintenance. It is inherited in an autosomal dominant pattern, meaning that having one altered copy of the gene can be enough to cause the disorder. This inheritance pattern also means that family members may be at risk, and the variability in symptoms among affected individuals underscores the concept of variable expressivity. Genetic counseling is recommended to help families understand the implications of this inheritance.

Management of autosomal dominant childhood-onset proximal spinal muscular atrophy without contractures centers on targeted therapies and supportive care. Currently, FDA-approved treatments include SPINRAZA (nusinersen) and EVRYSDI (risdiplam), as well as the FDA-approved gene therapy Zolgensma (onasemnogene abeparvovec-xioi), each of which may help improve motor function and quality of life for eligible individuals. While these treatments represent important advances, therapeutic decisions should be individualized, and patients should discuss options with their healthcare team. Genetic counseling is also recommended to provide guidance for affected families.

Autosomal dominant childhood-onset proximal spinal muscular atrophy without contractures is a lifelong neuromuscular condition with outcomes that vary widely from one individual to another. With current standards of care and ongoing therapeutic advances, many individuals experience periods of stability and continue to make developmental progress, although challenges in motor function and developmental aspects may persist. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists familiar with this condition and to seek genetic counseling for further guidance on management and future planning.