X-linked spinal muscular atrophy (XL-SMA) is one type of a group of conditions known as spinal muscular atrophies (SMAs), which are inherited disorders that cause muscle weakness and a loss of muscle tissue (atrophy). Symptoms of XL-SMA are usually present at birth and include low muscle tone (hypotonia), abnormal or absent reflexes (areflexia), abnormal muscle shortening that causes stiff joints (contractures), and broken bones (fractures). As the disease becomes worse with time (progresses), the muscles in the chest become weak, causing significant feeding and breathing problems. This is a serious condition that shortens the lifespan of most affected children.
XL-SMA is due to a change (mutation) in the UBE1 gene, which leads to a loss of specialized cells (lower motor neurons). The lower motor neurons are responsible for carrying signals from the brain to the muscles of the body. When the UBE1 gene is mutated, it causes the lower motor neurons to die off, leading to the muscle weakness and atrophy in this condition. XL-SMA is inherited in an X-linked recessive way, which means males are primarily affected. Males have one X chromosome (one copy of the UBE1 gene) while females have two X chromosomes (two copies of the UBE1). If a male has a mutation in their only copy, they will have XL-SMA. If females have a mutation in one of their two copies, it is not enough to cause the condition. Unaffected females with one mutation are called carriers and they are at risk of having an affected male child.
The diagnosis of XL-SMA is considered in a baby who is born with severe muscle weakness, contractures, and fractures. Genetic testing is used to confirm the diagnosis. Current treatment options are aimed at managing the symptoms of XL-SMA, including feeding and breathing support. If your child has been diagnosed with XL-SMA, talk with a doctor about all treatment options. Support groups are also available for additional information.