autosomal dominant childhood-onset proximal spinal muscular atrophy

Autosomal dominant childhood-onset proximal spinal muscular atrophy is a neuromuscular condition that primarily affects motor function in the proximal muscles, particularly in the lower extremities. It is associated with genetic alterations in BICD2 and DYNC1H1, two genes that play important roles in intracellular transport and neuronal function. The condition typically presents in childhood with muscle weakness and challenges in mobility. It is very rare, affecting fewer than 1 in 1,000,000 people.

The clinical presentation of this condition centers on muscle weakness, which is most noticeable in the muscles closest to the trunk and particularly in the lower limbs. Affected children may experience difficulties with ambulation and performing activities that require proximal muscle strength. Although no specific characteristic findings have been detailed in the available data, it is recognized that not all individuals experience all features, and severity varies considerably.

The condition is linked to pathogenic variants in the BICD2 and DYNC1H1 genes. These genes are responsible for producing proteins that are crucial for proper cellular transport and motor neuron function. Disruption in these proteins leads to impaired motor control and muscle weakness. Based on the primary name, the condition is inherited in an autosomal dominant manner, meaning that a single altered copy of the gene is sufficient to cause the disorder. Families are encouraged to seek genetic counseling to fully understand the implications and inheritance risks.

Management of this condition involves both targeted therapies and supportive care. Currently, FDA-approved treatments include SPINRAZA (nusinersen) and EVRYSDI (risdiplam), and an FDA-approved gene therapy, Zolgensma (onasemnogene abeparvovec-xioi), is available. In addition to these treatment options, a multidisciplinary approach that includes physical therapy, respiratory care, and regular monitoring is essential to manage symptoms and maintain function. Patients should discuss treatment options with their healthcare team to determine which therapies may be most appropriate for their specific situation, and genetic counseling is recommended to understand family planning options.

Outcomes for individuals with autosomal dominant childhood-onset proximal spinal muscular atrophy vary considerably, with the degree and progression of muscle weakness differing from person to person. With current standards of care, many individuals are able to achieve a stable quality of life, although the condition may progress or remain stable over time. Outcomes described in medical literature continue to evolve as standards of care improve. Families are encouraged to connect with genetic counselors and specialist care teams who can provide additional support and guidance for managing the condition over the long term.