Spinal muscular atrophy with lower extremity predominance 1

A rare genetic disorder affecting motor neurons

Spinal muscular atrophy with lower extremity predominance 1 (SMA-LED1) is a rare genetic disorder characterized by progressive muscle weakness and atrophy, primarily affecting the lower limbs. It is a form of spinal muscular atrophy (SMA) that is distinct due to its autosomal dominant inheritance pattern and its specific impact on the lower extremities.

Genetics

SMA-LED1 is caused by mutations in the DYNC1H1 gene, which encodes a protein that is part of the cytoplasmic dynein complex. This complex is crucial for intracellular transport processes, including the movement of organelles and other cellular components along microtubules. Mutations in DYNC1H1 disrupt these processes, leading to the degeneration of motor neurons and subsequent muscle weakness.

Autosomal dominant inheritance pattern

The disorder follows an autosomal dominant inheritance pattern, meaning that a single copy of the mutated gene inherited from an affected parent can cause the disease. This pattern of inheritance is depicted in the accompanying image.

Clinical Features

Individuals with SMA-LED1 typically present with symptoms in early childhood, although the age of onset can vary. The primary clinical feature is muscle weakness that predominantly affects the lower limbs. This weakness can lead to difficulties with walking, running, and other activities that require lower body strength. Over time, muscle atrophy may become apparent, and affected individuals may develop a characteristic gait.

Diagnosis

The diagnosis of SMA-LED1 is based on clinical evaluation, family history, and genetic testing. Genetic testing can confirm the presence of mutations in the DYNC1H1 gene. Electromyography (EMG) and nerve conduction studies may also be used to assess the extent of motor neuron involvement.

Management

There is currently no cure for SMA-LED1, and treatment is primarily supportive. Management strategies may include physical therapy to maintain mobility and prevent contractures, as well as orthopedic interventions if necessary. Genetic counseling is recommended for affected families to discuss inheritance patterns and reproductive options.

Prognosis

The prognosis for individuals with SMA-LED1 varies depending on the severity of the symptoms and the rate of progression. While the disorder primarily affects the lower limbs, it does not typically impact life expectancy. However, the degree of disability can vary, and some individuals may require assistive devices for mobility.

Related pages

• Spinal muscular atrophy
• Motor neuron disease
• Genetic disorder