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Spinal muscular atrophy with lower extremity predominance
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Conditions

Spinal muscular atrophy with lower extremity predominance

Spinal muscular atrophy with lower extremity predominance (SMA-LED) is a genetic condition characterized by muscle weakness and wasting, primarily affecting the thigh muscles.

Overview

SMA-LED is characterized by muscle weakness and wasting (atrophy) in the lower limbs, most severely affecting the thigh muscles (quadriceps). The loss of motor neurons leads to atrophy of the muscles in the lower limbs. Affected individuals often have a waddling or unsteady walk and walk on the balls of their feet. They may have difficulty rising from a seated position and climbing stairs. Some people with SMA-LED also have weakness in upper limb muscles.

Joint deformities (contractures) in the hips, knees, feet, and ankles can occur in SMA-LED, and in severe cases are present from birth and can impair walking. Some individuals have rigidity of joints (arthrogryposis) in their shoulders, elbows, and hands.

In most people, muscle problems are apparent in infancy or early childhood; however, about one-quarter of affected individuals do not develop muscle weakness until adulthood. The muscle weakness and related health problems typically do not worsen over time.

Frequency

SMA-LED is thought to be a rare condition; its prevalence is unknown.

Causes

SMA-LED is caused by mutations in the DYNC1H1 gene or BICD2 gene. When caused by DYNC1H1 mutations, it is often known as SMA-LED type 1 (SMA-LED1); when caused by BICD2 mutations, it is known as SMA-LED type 2 (SMA-LED2).

Cellular Impact

The DYNC1H1 gene provides instructions for making a protein that is part of the dynein complex, which transports materials within cells. The BICD2 protein activates the dynein complex and helps it bind to cellular materials. These proteins help neurons communicate by transporting synaptic vesicles containing chemical messengers. BICD2 also helps maintain the structure of the Golgi apparatus.

Mutations disrupt the function of the dynein complex, reducing the transport of proteins and synaptic vesicles. Decreased synaptic vesicle transport in motor neurons leads to impaired growth of neurons, contributing to muscle weakness and atrophy. Additionally, BICD2 mutations impair the protein's ability to maintain the Golgi apparatus, causing it to break down into fragments, which likely further contributes to the symptoms.

Associated Genes

  • BICD2
  • DYNC1H1

Inheritance

This condition is inherited in an autosomal dominant pattern, meaning one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from an affected parent. Other cases result from new mutations and occur in people with no history of the disorder in their family.

Other Names

  • Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures
  • Kugelberg-Welander syndrome, autosomal dominant
  • Lower extremity-predominant autosomal dominant proximal spinal muscular atrophy with contractures
  • SMA-LED
  • Spinal muscular atrophy, childhood, proximal, autosomal dominant
  • Spinal muscular atrophy, juvenile, proximal, autosomal dominant
  • Spinal muscular atrophy, lower extremity, autosomal dominant
  • Spinal muscular atrophy, lower extremity, dominant

Frequently Asked Questions

The test is a blood draw for DNA sequencing of the DYNC1H1 and BICD2 genes. No special preparation is required; fasting is not necessary. Genetic counseling before and after testing helps interpret results and discuss implications for family planning.
multidisciplinary approach is essential: physical therapy focused on strengthening the quadriceps and hip abductors, stretching to maintain range of motion, use of ankle‑foot orthoses to support the feet, and, if needed, surgical release of tight tendons or joint contractures. Assistive devices such as canes or walkers, and in some cases, orthotic braces, can improve gait stability.
Key clues are early onset (often within the first year of life), predominant weakness of the thigh muscles causing a waddling gait, relatively preserved upper‑limb strength, and a normal or only mildly affected reflex pattern. An EMG showing chronic denervation in the lower limbs and genetic testing for DYNC1H1 or BICD2 mutations can confirm the diagnosis.
SMA‑LED is typically a non‑progressive or slowly progressive condition; muscle weakness stabilizes after early childhood. With ongoing therapy, many adults maintain independent ambulation, though they may experience fatigue or mild gait difficulties. Regular physiotherapy and early intervention for contractures help preserve function and quality of life.===
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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