Rigid spine muscular dystrophy (RSMD) is a form of congenital muscular dystrophy. Disorders in this group cause muscle weakness and wasting (atrophy) beginning very early in life. In particular, RSMD involves weakness of the muscles of the torso and neck (axial muscles). Other characteristic features include spine stiffness and serious breathing problems.

In RSMD, muscle weakness is often apparent at birth or within the first few months of life. Affected infants can have poor head control and weak muscle tone (hypotonia), which may delay the development of motor skills such as crawling or walking. Over time, muscles surrounding the spine atrophy, and the joints of the spine develop deformities called contractures that restrict movement. The neck and back become stiff and rigid, and affected children have limited ability to move their heads up and down or side to side. Affected children eventually develop an abnormal curvature of the spine (scoliosis). In some people with RSMD, muscles in the inner thighs also atrophy, although it does not impair the ability to walk.

A characteristic feature of RSMD is breathing difficulty (respiratory insufficiency) due to restricted movement of the torso and weakness of the diaphragm, which is the muscle that separates the abdomen from the chest cavity. The breathing problems, which tend to occur only at night, can be life-threatening. Many affected individuals require a machine to help them breathe (mechanical ventilation) during sleep.

The combination of features characteristic of RSMD, particularly axial muscle weakness, spine rigidity, and respiratory insufficiency, is sometimes referred to as rigid spine syndrome. While these features occur on their own in RSMD, they can also occur along with additional signs and symptoms in other muscle disorders. The features of rigid spine syndrome typically appear at a younger age in people with RSMD than in those with other muscle disorders.

Mutations in a gene called SELENON (formerly SEPN1) cause about 40 percent of cases of RSMD. When caused by mutations in this gene, the condition is known as rigid spine muscular dystrophy 1 (RSMD1). The genetic cause of the remainder of cases is unknown.

The SELENON gene provides instructions for making a protein known as selenoprotein N. The specific job of selenoprotein N is unknown, but researchers suspect it plays a role in the formation of muscle tissue before birth. It may also be important for normal muscle function after birth. The gene mutations that cause RSMD1 are thought to reduce the amount of selenoprotein N or impair its activity in cells. It is unclear how a shortage of working selenoprotein N leads to muscle weakness and other features of RSMD1.

RSMD1 is part of a spectrum of muscle disorders called SELENON-related (or SEPN1-related) myopathy, which also includes the classic form of multiminicore disease, desmin-related myopathy with Mallory body-like inclusions, and a small subset of cases of congenital fiber-type disproportion. While these other disorders share the characteristic features of RSMD1, they each also involve distinctive abnormalities of the muscle fibers that can only be seen when viewed under a microscope. Because these conditions have a similar pattern of signs and symptoms and are caused by mutations in the same gene, many researchers believe that they are all part of a single syndrome with variable signs and symptoms. It is unclear why mutations in the SELENON gene cause the different muscle fiber abnormalities that distinguish the separate conditions.

Normal Function

The SELENON gene (also called SEPN1) provides instructions for making a protein called selenoprotein N. This protein is part of a family of selenoproteins, which have several critical functions within the body. Selenoproteins are primarily involved in chemical reactions called oxidation-reduction reactions, which are essential for protecting cells from damage caused by unstable oxygen-containing molecules. Although the exact function of selenoprotein N is unknown, it is likely involved in protecting cells against oxidative stress. Oxidative stress occurs when unstable molecules called free radicals accumulate to levels that damage or kill cells.

Selenoprotein N is highly active in many tissues before birth and may be involved in the formation of muscle tissue (myogenesis). The protein may also be important for normal muscle function after birth, although it is active at much lower levels in adult tissues. This protein is thought to play a role in maintaining an appropriate balance of calcium (calcium homeostasis) in cells. Calcium plays an important role in muscle movement.

Health Conditions Related to Genetic Changes

Multiminicore disease

At least 17 mutations in the SELENON gene have been identified in people with the classic form of multiminicore disease. This condition is named for a distinctive abnormality in the muscle fibers called minicores (which can only be seen with a microscope). In addition, affected individuals have muscle weakness, particularly in the muscles of the torso and neck (the axial muscles); abnormal curvature of the spine (scoliosis); and serious breathing problems. Many of the genetic changes that cause classic multiminicore disease lead to the production of an abnormally short version of selenoprotein N. Other mutations change single protein building blocks (amino acids) in critical regions of the protein. The effects of changes in the structure and function of selenoprotein N are unknown, and researchers are working to determine how these changes lead to muscle weakness and the other characteristic features of classic multiminicore disease.

Rigid spine muscular dystrophy

More than a dozen SELENON gene mutations have been found to cause rigid spine muscular dystrophy 1 (RSMD1). In people with this disorder, the muscles surrounding the spine weaken and waste away (atrophy), and the joints in the spine develop deformities called contractures that restrict movement. Affected children have limited ability to move their heads up and down or side to side. They also develop scoliosis and have serious breathing problems during sleep.

The SELENON gene mutations that cause RSMD1 are thought to reduce the amount of selenoprotein N or impair its activity in cells. It is unclear how a shortage of functional selenoprotein N affects the formation of muscle tissue or the function of muscles. Researchers are working to determine why axial muscles are particularly affected by SELENON gene mutations.

Congenital fiber-type disproportion

MedlinePlus Genetics provides information about Congenital fiber-type disproportion

Other disorders

Mutations in the SELENON gene are involved in another rare muscle disorder called desmin-related myopathy with Mallory body-like inclusions. This disorder is characterized by the presence of small clusters of accumulated proteins in the muscle fibers. These abnormal regions can only be seen when muscle tissue is viewed under a microscope. The inclusions resemble an abnormality known as Mallory bodies. As in other SELENON-related muscle disorders (described above), desmin-related myopathy with Mallory body-like inclusions is characterized by axial muscle weakness, spine stiffness, scoliosis, and serious breathing problems. Because they have a similar pattern of signs and symptoms and are caused by mutations in the same gene, many researchers believe that these conditions are all part of a single syndrome with variable signs and symptoms. Together, muscle diseases caused by SELENON gene mutations are known as SELENON-related (or SEPN1-related) myopathy. It is unclear why mutations in the SELENON gene cause the different muscle fiber abnormalities that distinguish these disorders.

Other Names for This Gene

• selenoprotein N, 1
• SELN
• SEPN1
• SEPN1_HUMAN

Genomic Location

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

RSMD is thought to be a rare disorder, although its prevalence is unknown.