spinal muscular atrophy, type 1

Spinal muscular atrophy, type 1 is a severe infantile condition characterized by progressive muscle weakness and hypotonia due to the degeneration of lower motor neurons in the spinal cord and brain stem. The disorder is caused by variants in the SMN1 gene, which disrupt the production of a protein essential for motor neuron survival. It primarily affects infants, presenting early in life with markedly reduced motor capabilities. In terms of prevalence, this condition is uncommon, affecting approximately 1 to 9 individuals per 100,000 people.

Affected infants typically present with profound muscle weakness and low muscle tone, making spontaneous movements and motor milestones difficult to achieve. A characteristic clinical feature is decreased fetal movement, which is observed in a significant proportion of cases. As the disease progresses, muscle degeneration leads to further motor impairment and respiratory challenges, although not all individuals experience every symptom and severity can vary widely. Not all individuals experience all features, and severity varies considerably.

Spinal muscular atrophy, type 1 results from pathogenic variants in the SMN1 gene, which plays a crucial role in the survival and maintenance of motor neurons. The reduced function or absence of the SMN1 gene product leads to the degeneration of motor neurons and subsequent muscle weakness. This condition is inherited in an autosomal recessive pattern, meaning that an affected individual has inherited one altered copy of the gene from each parent. Families are encouraged to seek genetic counseling to understand the implications for current and future pregnancies.

Management of spinal muscular atrophy, type 1 focuses on a multidisciplinary approach, as foundational therapies such as standard supportive care are essential for symptom management. In addition to supportive measures, several targeted treatments are available. Currently approved treatments include FDA-approved options such as SPINRAZA (nusinersen) and EVRYSDI (risdiplam), as well as the FDA-approved gene therapy Zolgensma (onasemnogene abeparvovec-xioi), which specifically targets the underlying genetic defect in eligible patients. Patients should discuss treatment options with their healthcare team to determine which therapies may be appropriate for their specific situation, and genetic counseling is recommended for inherited conditions.

The prognosis for spinal muscular atrophy, type 1 is highly variable and depends on factors such as the severity of the symptoms, age at diagnosis, and access to specialized care. This lifelong neurodevelopmental condition is characterized by an initial period of significant motor impairment, and while early challenges are profound, advances in treatment have improved outcomes for many individuals. Outcomes described in medical literature continue to evolve as standards of care improve, and families are encouraged to connect with genetic counselors and specialists to better understand individual risks and care options. Continuous monitoring and multidisciplinary support can help optimize quality of life despite the challenges posed by the condition.

This is an active research area, and several clinical trials are currently investigating new treatment approaches for spinal muscular atrophy, type 1. Individuals interested in clinical trials are encouraged to consult ClinicalTrials.gov or speak with their care team to learn about eligibility and emerging therapeutic options.