Spinal muscular atrophy with lower extremity predominance 1

Spinal Muscular Atrophy with Lower Extremity Predominance 1 (SMA-LED1), also known as Spinal Muscular Atrophy, Lower Extremity-Predominant 1, is a rare neuromuscular disorder characterized by muscle weakness and atrophy predominantly affecting the lower limbs. SMA-LED1 is a subtype of Spinal Muscular Atrophy (SMA) which is a group of hereditary diseases that progressively destroys motor neurons—nerve cells in the brain stem and spinal cord that control essential skeletal muscle activity such as speaking, walking, breathing, and swallowing, leading to muscle weakness and atrophy.

Genetics

SMA-LED1 is caused by mutations in the DYNC1H1 gene, which encodes for a subunit of the dynein cytoplasmic motor protein that is involved in the retrograde transport along microtubules. The DYNC1H1 gene mutations lead to the impairment of motor neuron function and survival, specifically affecting the lower limbs. This condition is inherited in an autosomal dominant manner, meaning that only one copy of the altered gene in each cell is sufficient to cause the disorder.

Symptoms and Diagnosis

The primary symptoms of SMA-LED1 include muscle weakness and atrophy predominantly in the lower extremities, which can lead to difficulty walking, frequent falls, and in severe cases, the need for wheelchair assistance. The onset of symptoms typically occurs in infancy or early childhood. Diagnosis of SMA-LED1 is based on clinical examination, family history, and genetic testing to identify mutations in the DYNC1H1 gene. Electromyography (EMG) and muscle biopsy may also be used to assess the extent of muscle involvement and to rule out other conditions.

Treatment and Management

There is currently no cure for SMA-LED1, and treatment focuses on managing symptoms and improving quality of life. Physical therapy and rehabilitation exercises are recommended to strengthen muscles and improve mobility. Orthopedic interventions may be necessary to address skeletal deformities such as scoliosis or hip dislocation. In some cases, assistive devices such as braces or wheelchairs may be required to aid in mobility. Regular follow-up with a multidisciplinary team of healthcare providers, including neurologists, orthopedists, and physical therapists, is essential for optimal management of the condition.

Prognosis

The prognosis for individuals with SMA-LED1 varies depending on the severity of symptoms and the onset of the disease. Early intervention and comprehensive management can help to improve mobility and quality of life. However, SMA-LED1 is a progressive condition, and individuals may experience increasing difficulty with walking and require more assistance over time.

NIH genetic and rare disease info

• NIH info on Spinal muscular atrophy with lower extremity predominance 1

Spinal muscular atrophy with lower extremity predominance 1 is a rare disease.