autosomal recessive distal spinal muscular atrophy 2

Autosomal recessive distal spinal muscular atrophy 2 is a rare neuromuscular condition that primarily affects the distal muscles of the limbs. It is characterized by progressive and symmetrical muscle weakness and atrophy, with initial symptoms appearing in the lower limbs during the later part of the first decade and progressing to the upper limbs within approximately two years. Variants in the SIGMAR1 gene underlie this condition, and its autosomal recessive inheritance means that both parents must carry a copy of the altered gene. As it affects fewer than 1 in 1,000,000 individuals, the condition is considered extremely uncommon.

The clinical presentation of autosomal recessive distal spinal muscular atrophy 2 is defined by progressive distal muscle weakness and atrophy. Affected individuals typically experience foot drop, pes varus, hammer toes, and claw hands, with characteristic findings such as distal amyotrophy, foot dorsiflexor weakness, absent Achilles reflex, decreased compound muscle action potential amplitude, decreased motor nerve conduction velocity, and hyperactive patellar reflex being almost universally observed. Additionally, features like a positive Babinski sign and claw hand deformity are seen in a subset of patients. Not all individuals experience all features, and severity varies considerably.

This condition is caused by pathogenic variants in the SIGMAR1 gene. It is inherited in an autosomal recessive pattern, meaning that an affected individual has received one altered copy of the gene from each parent. Autosomal recessive conditions like this one are more common when parents share a common ancestor, as both are more likely to carry the same rare pathogenic variant. Genetic counseling is recommended for families to discuss recurrence risks and implications for family planning.

Management of autosomal recessive distal spinal muscular atrophy 2 involves targeted therapies, including FDA-approved treatments such as SPINRAZA (nusinersen) and EVRYSDI (risdiplam), as well as the FDA-approved gene therapy Zolgensma (onasemnogene abeparvovec-xioi) which is regulated by the FDA's Center for Biologics Evaluation and Research. Although there are no foundational therapies specifically listed, treatment is typically tailored to the individual through a multidisciplinary approach that may include physical therapy, occupational therapy, and other supportive care strategies. Patients should discuss treatment options with their healthcare team, and genetic counseling is recommended to address inheritance concerns and family planning.

The course of autosomal recessive distal spinal muscular atrophy 2 is lifelong and can vary widely among affected individuals. Typically, the condition presents with progressive muscle weakness that eventually stabilizes, with pyramidal tract signs present initially and then regressing around 10 years after onset. Outcomes depend on several factors including the severity of symptoms, age at diagnosis, and access to specialized care, with modern standards of care contributing to improved quality of life. Outcomes described in medical literature continue to evolve as standards of care improve. Families are encouraged to connect with genetic counselors and specialists to gain personalized insights and to explore support resources available for managing this condition.