Autosomal dominant proximal spinal muscular atrophy

Autosomal dominant proximal spinal muscular atrophy (AD-SMA) is a rare genetic neuromuscular disorder characterized by degeneration of the motor neurons in the anterior horn of the spinal cord, leading to progressive proximal muscle weakness and atrophy. Unlike the more common autosomal recessive forms of spinal muscular atrophy (caused by SMT1 gene mutations), this condition follows an autosomal dominant inheritance pattern. The disease primarily affects the neuromuscular system, with weakness predominantly involving the proximal muscles of the limbs — particularly the shoulders, upper arms, hips, and thighs — making activities such as climbing stairs, rising from a seated position, and lifting objects increasingly difficult. Clinical features may vary in severity and age of onset. Patients typically present with slowly progressive proximal limb weakness, muscle wasting, and reduced or absent deep tendon reflexes. Some individuals may also experience fasciculations (involuntary muscle twitching). The lower extremities are often more affected than the upper extremities. Respiratory function may be preserved longer compared to severe recessive forms, though monitoring is important as the disease progresses. Bulbar involvement is generally uncommon but may occur in some cases. There is currently no curative treatment for autosomal dominant proximal spinal muscular atrophy. Management is primarily supportive and multidisciplinary, including physical therapy to maintain mobility and prevent contractures, occupational therapy, orthopedic interventions as needed, and respiratory monitoring. Genetic counseling is recommended for affected families given the 50% risk of transmission to offspring. Research into targeted therapies for motor neuron diseases is ongoing, but specific disease-modifying treatments for this particular form have not yet been established.

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