autosomal recessive distal spinal muscular atrophy 1

Autosomal recessive distal spinal muscular atrophy 1 is a rare genetic motor neuron disease that primarily affects infants, presenting with severe respiratory distress and progressive muscle weakness. This condition is caused by pathogenic variants in the IGHMBP2 gene, which disrupt normal motor neuron function leading to characteristic diaphragmatic eventration and muscle atrophy. Affected newborns often have a history of intrauterine growth retardation, low birth weight, and feeding difficulties. The condition is very rare, affecting fewer than 1 in one million people.

Clinically, affected infants present with neonatal hypotonia and diaphragmatic eventration, which are consistently observed in all cases. Early features include a feeble cry, weak suck, and failure to thrive, often accompanied by inspiratory stridor, episodes of difficulty breathing, apnea, and cyanosis. As the condition progresses, patients may develop additional musculoskeletal issues such as kyphosis or scoliosis, foot deformities, and joint contractures, while talipes equinovarus appears in a subset of individuals. Not all individuals experience all features, and severity varies considerably.

Autosomal recessive distal spinal muscular atrophy 1 is caused by pathogenic variants in the IGHMBP2 gene. This gene plays an important role in maintaining motor neuron function, and disruptions in its activity lead to the characteristic muscle weakness and respiratory distress observed in the condition. Inheritance is autosomal recessive, meaning that an affected individual has inherited two copies of the altered gene, one from each parent. This condition is more common when parents share a common ancestor, as the likelihood of both carrying the same rare genetic variant increases, although the recurrence risk remains 25% per pregnancy. Genetic counseling is recommended to help families understand these risks and implications for family planning.

Management of autosomal recessive distal spinal muscular atrophy 1 involves multidisciplinary care tailored to the individual’s needs. Supportive care plays a central role in addressing respiratory difficulties and ensuring adequate nutritional support. In addition to supportive measures, several FDA-approved treatments are available to target the underlying condition, including SPINRAZA (nusinersen), EVRYSDI (risdiplam), and the FDA-approved gene therapy Zolgensma (onasemnogene abeparvovec-xioi). Patients and families are encouraged to discuss treatment options with their healthcare team, which typically includes genetic counseling and input from neuromuscular specialists.

The course of autosomal recessive distal spinal muscular atrophy 1 is variable, with outcomes largely dependent on the severity of respiratory involvement and muscle weakness. With current standards of care, many individuals benefit from improved respiratory management and multidisciplinary support, which have led to better quality of life and more favorable outcomes compared to earlier descriptions. Outcomes described in medical literature continue to evolve as standards of care improve. Families are advised to seek genetic counseling and connect with specialists to better understand the potential variability and to receive personalized guidance for long-term management.

There are clinical trials currently underway exploring new treatment approaches for this condition. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about potential eligibility for emerging therapies.