Myoclonus-dystonia is a movement disorder that typically affects the neck, torso, and arms. Individuals with this condition experience quick, involuntary muscle jerks or twitches (myoclonus). About half of individuals with myoclonus-dystonia develop dystonia, which is involuntary tensing of various muscles that causes unusual positioning. In myoclonus-dystonia, dystonia often affects one or both hands, causing writer's cramp, or the neck, causing the head to turn (torticollis).

The movement problems usually first appear in childhood or early adolescence with the development of myoclonus. In most cases, the movement problems remain stable throughout life. In some adults, myoclonus improves with alcohol consumption, which can lead to affected individuals self-medicating and developing alcohol use disorder.

People with myoclonus-dystonia often develop psychological disorders such as depression, anxiety, panic attacks, and obsessive-compulsive disorder (OCD).

Mutations in the SGCE gene cause 30 to 50 percent of cases of myoclonus-dystonia. The SGCE gene provides instructions for making a protein called epsilon (ε)-sarcoglycan, whose function is unknown. The ε-sarcoglycan protein is located within the outer membrane of cells in many tissues, but it is most abundant in nerve cells (neurons) in the brain and in muscle cells.

SGCE gene mutations that cause myoclonus-dystonia result in a shortage (deficiency) of functional ε-sarcoglycan protein. This lack of functional protein seems to affect the regions of the brain involved in coordinating and controlling movements (the cerebellum and basal ganglia, respectively). It is unknown why SGCE gene mutations seem to affect only these areas of the brain.

Mutations in multiple other genes are associated with myoclonus-dystonia. Mutations in each of these genes cause a small percentage of cases. These genes are primarily active (expressed) in the brain and mutations likely lead to impairment of normal movement.

Some people with myoclonus-dystonia do not have an identified mutation in any of the known associated genes. The cause of the condition in these individuals is unknown.

Normal Function

The SGCE gene provides instructions for making a protein called epsilon (ε)-sarcoglycan, whose function is unknown. The ε-sarcoglycan protein is found within the outer membrane of cells in tissues throughout the body, but it is most abundant in nerve cells (neurons) in the brain and in muscle cells. Researchers suspect that in the brain the ε-sarcoglycan protein plays a role in the functioning of synapses, which are the connections between neurons where cell-to-cell communication occurs.

People inherit one copy of most genes from their mother (the maternal copy) and one copy from their father (the paternal copy). Both copies are typically active, or "turned on," in cells. However, only the paternal copy of the SGCE gene is active. This sort of parent-specific difference in gene activation is caused by a phenomenon called genomic imprinting.

Health Conditions Related to Genetic Changes

Myoclonus-dystonia

More than 110 mutations in the SGCE gene have been found to cause myoclonus-dystonia, which is a movement disorder characterized by involuntary muscle twitches in the neck, torso, and arms (myoclonus). Most of these mutations lead to an abnormally short, nonfunctional ε-sarcoglycan protein that is quickly broken down. Other mutations prevent the protein from reaching the cell membrane where it is needed. This lack of functional protein seems to affect the regions of the brain involved in coordinating and controlling movements (the cerebellum and basal ganglia, respectively) and leads to the involuntary movements characteristic of myoclonus-dystonia. It is unknown why SGCE gene mutations seem to affect only these areas of the brain.

Myoclonus-dystonia occurs when mutations affect the paternal copy of the SGCE gene. More than 95 percent of individuals who inherit an SGCE gene mutation from their mothers do not show signs or symptoms of the condition. Rarely, individuals who inherit an SGCE gene mutation from their mothers will develop features of myoclonus-dystonia. It is unclear why a gene that is supposed to be turned off is active in these rare cases.

Other Names for This Gene

• DYT11
• ESG
• sarcoglycan, epsilon
• SGCE_HUMAN

Genomic Location

In cases in which the genetic cause is known, myoclonus-dystonia is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In cases in which the cause of the condition is unknown, the inheritance is unclear.

When caused by SGCE gene mutations, myoclonus-dystonia occurs only when the mutation is inherited from a person's father. People normally inherit one copy of each gene from their mother and one copy from their father. For most genes, both copies are active, or "turned on," in all cells. For a small subset of genes, however, only one of the two copies is active. For some of these genes, only the copy inherited from a person's father (the paternal copy) is active, while for other genes, only the copy inherited from a person's mother (the maternal copy) is active. These differences in gene activation based on the gene's parent of origin are caused by a phenomenon called genomic imprinting.

Because only the paternal copy of the SGCE gene is active, myoclonus-dystonia occurs when mutations affect the paternal copy of the SGCE gene. Mutations in the maternal copy of the gene typically do not cause any health problems. Rarely, individuals who inherit an SGCE gene mutation from their mothers will develop features of myoclonus-dystonia. It is unclear why a gene that is supposed to be turned off is active in these rare cases.

Other genes associated with myoclonus-dystonia are not imprinted, and mutations that cause the condition can be inherited from either parent.

The prevalence of myoclonus-dystonia in Europe is estimated to be 1 in 500,000 individuals. Its prevalence elsewhere in the world is unknown.