autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures

Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures is a neuromuscular disorder primarily affecting the muscles of the lower limbs. It is caused by pathogenic variants in the BICD2 gene, which is important for intracellular transport and muscle function. Affected children typically develop symptoms in early childhood, and the condition is extremely rare, affecting fewer than 1 in 1,000,000 individuals. The severity of symptoms varies from one individual to another.

Individuals with this condition characteristically exhibit profound lower limb muscle weakness, with the proximal muscles being especially affected. A waddling gait, decreased Achilles reflex, and, in many cases, scapular winging and reduced patellar reflexes are common features. In addition, some patients may experience postexertional symptom exacerbation, lower limb amyotrophy, and the development of contractures, such as Achilles tendon contracture. Not all individuals experience every feature, and severity varies widely between affected individuals.

This condition is linked to pathogenic variants in the BICD2 gene, which plays a crucial role in intracellular transport and proper muscle function. It is inherited in an autosomal dominant pattern, meaning that the presence of a single altered copy of BICD2 is sufficient to cause the condition. As a result, an affected parent has a 50% chance of passing the variant to each child, although the severity and specific symptoms can differ significantly between family members due to variable expressivity.

Management of this condition involves a multidisciplinary approach tailored to the patient's unique needs. FDA-approved treatments include SPINRAZA (nusinersen) and EVRYSDI (risdiplam), along with the FDA-approved gene therapy Zolgensma (onasemnogene abeparvovec-xioi), which may be considered for certain patients based on eligibility criteria. In addition to these targeted therapies, regular surveillance is an essential part of long-term care, with ongoing monitoring to detect changes in muscle strength, respiratory function, and the development of contractures. Patients are encouraged to work closely with their healthcare team and seek genetic counseling to better understand treatment options and implications for family planning.

The clinical course of this condition is highly variable, with some individuals maintaining steady function while others experience gradual changes over time. With current standards of care and access to approved therapies, many individuals achieve improvements in quality of life and sustained function. Outcomes described in medical literature continue to evolve as standards of care improve, and families should consider connecting with specialists experienced in managing the condition to help guide long-term care decisions.