Spinal muscular atrophy (SMA) is a rare and heritable disease characterized by the loss of motor neurons, or nerve cells that control voluntary muscle movement. Without these nerve cells, muscles weaken and atrophy.

SMA with lower extremity predominance (SMA-LED) is a rare type of SMA that particularly affects the lower limbs.

Causes

SMA-LED is caused by mutations in the DYNC1H1 (dynein cytoplasmic 1 heavy chain 1) or the BICD2 (BICD cargo adaptor 2) gene. Both genes provide instructions for making proteins that are part of a protein complex called the dynein-dynactin complex, which is involved in moving materials within cells.

The dynein-dynactin complex binds to various materials within cells, moving them along a system of small tubes called microtubules. The dynein-dynactin complex has very important functions in protein transport, positioning of cell compartments, and the mobility of structures within cells (among other cell processes). In nerve cells, dynein helps neighboring cells to communicate by moving synaptic vesicles that contain chemical messengers.

In SMA-LED, mutations in either DYNC1H1 or BICD2 cause changes in the amino acid sequence (the building blocks of proteins). As a result, the movement of proteins and cellular materials is impaired, resulting in reduced chemical signaling among neurons that control muscle movement. Poor synaptic vesicle transport also affect nerve cell growth, and is thought to contribute to muscle weakness in patients.

Inheritance 

SMA-LED is inherited in an autosomal dominant manner, meaning that a single copy of the disease-causing mutation is sufficient to result in disease development. The children of people who are affected by SMA-LED have a 1-in-2 risk of inheriting the gene and developing the disease themselves.

Symptoms

SMA-LED is characterized by weakness in the leg muscles, with symptoms most pronounced in the quadriceps or large muscles of the thighs. Symptoms appear in infancy or childhood, but progress slowly. Typically, they include waddling or an unsteady walk or gait, and difficulties in rising from a seated position and in climbing stairs.

Research is not clear as to why this condition only affects a person’s lower extremities.

Treatment 

No cure currently exists for SMA-LED, but treatments can help to ease its symptoms and improve patients’ quality of life.

Outlook

Most patients with SMA-LED have a normal lifespan. Some may need support, such as braces or a wheelchair, for mobility later in life.

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SMA News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

Emily holds a Ph.D. in Biochemistry from the University of Iowa and is currently a postdoctoral scholar at the University of Wisconsin-Madison. She graduated with a Masters in Chemistry from the Georgia Institute of Technology and holds a Bachelors in Biology and Chemistry from the University of Central Arkansas. Emily is passionate about science communication, and, in her free time, writes and illustrates children’s stories.
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Emily holds a Ph.D. in Biochemistry from the University of Iowa and is currently a postdoctoral scholar at the University of Wisconsin-Madison. She graduated with a Masters in Chemistry from the Georgia Institute of Technology and holds a Bachelors in Biology and Chemistry from the University of Central Arkansas. Emily is passionate about science communication, and, in her free time, writes and illustrates children’s stories.
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