Myasthenia, Congenital

views updated May 21 2018

Myasthenia, congenital

Definition

Congenital myasthenia is an inherited disorder that results in muscle weakness caused by a malfunction at the neuromuscular junction, the area where nerve cells communicate to muscle cells.

Description

Congenital myasthenia is caused by a number of genetic defects that affect the ability of a nerve impulse to move from nerve to nerve, and from the nerve to muscle. The genetic abnormalities can be present in the fetus at the moment of conception or may occur during fetal development. This genetic cause of the disease separates the congenital form of myasthenia from myasthenia gravis and Lambert-Eaton myasthenic syndrome , both of which are caused by the malfunctioning of the immune system.

Demographics

Congenital myasthenia occurs in the young, and occurs with equal frequency in boys and girls. Symptoms tend to appear within the first two years of life. It is common to have siblings who are affected. The disease is extremely rare, occurring in only one to two per million live births.

Causes and symptoms

The root of congenital myasthenia are defects in various genes that play a role in the transmission of nerve impulses. At least a dozen genetic defects have been identified as causes of congenital myasthenic syndromes so far. The defects can affect the manufacture or the release of acetylcholine, a neurotransmitter, or molecule that acts as a communication bridge between adjacent nerves.

As a result of the varying genetic roots of the disease, different congenital myasthenic syndromes exist. These can produce different effects in those who are affected. The symptoms, which usually begin in infancy or toddlerhood, can include a poor sucking response, drooping eyelids (a condition called ptosis), eyes that appear to wander or float (ophthalmoplegia), weakness in facial muscles that is apparent as an abnormal appearance, weakness in the arms and legs, breathing difficulty, delayed development of muscle skills, and a feeling of fatigue . Usually, a parent may notice that the infant is experiencing delays in developmental milestones that require coordinated muscle strength, such as sitting up alone, crawling, or walking. All or just a few of these symptoms can be present in a person with congenital myasthenia. As well, the severity of the symptoms can vary from person to person. Some children may be severely impaired, while others lead near normal lives. Even though children display symptoms, their parents may not be similarly affected.

Diagnosis

The disease is usually diagnosed in the early years of childhood by the abnormal appearance of the face and/or by the noticeable weakening of the arms or legs. A test of muscle strength known as the tensilon test that is considered to be accurate in diagnosis of other forms of myasthenia is usually not specific for congenital myasthenia. Congenital myasthenia is often misdiagnosed as myasthenia gravis or other neuromuscular diseases.

Accurate diagnosis of congenital myasthenia requires specialized testing. These include testing specific nerves to determine if the nerves fatigue more quickly than is normal. While at least a dozen genes that are responsible for the disease are known, genetic testing technology is not currently routinely available. Only a handful of centers in the United States are able to test the anconeus and intercostal muscles to detect the abnormal genes. However, as such technology becomes routine (i.e., gene chips), genetic testing will no doubt become one of the principle means of diagnosis.

Treatment team

Treatment can involve the family physician, a neurologist , family members, and physical therapists. The latter can provide exercises that assist in maximizing muscular strength.

Treatment

Treatment for most types of congenital myasthenia typically involves the use of drugs that help promote the transmission of nerve impulses. Drugs that retard the breakdown of acetylcholine can be used. An example of an acetylcholine sterase is mestinon. Other drugs that show merit in some cases include guanidine, ephedrine sulfate, and albuterol. People may build up a tolerance to ephedrine, which decreases its effectiveness.

Recovery and rehabilitation

As there is no recovery from congenital myasthenia, treatment is aimed at maximizing muscle function through drug therapy and physical therapy.

Clinical trials

As of mid-2004, there were no clinical trials underway or in the planning stages specific for congenital myasthenia. However, agencies such as the National Institute for Neurological Diseases and Stroke continue to fund research that seeks to better understand the underlying genetic bases of congenital myasthenia, and to discover more effective means of increasing nerve signal transmission. Updated information on clinical trials related to congenital myasthenia can be located at the National Institutes of Health website for clinical trials at www.clinicaltrials.org.

Prognosis

With accurate diagnosis, most types of congenital myasthenia can be improved or at least stabilized by the use of drug therapy. More severe forms of the disease may weaken respiratory muscles and result in a reduced lifespan.

Resources

BOOKS

Thompson, Charlotte. Raising a Child with a Neuromuscular Disorder: A Guide for Parents, Grandparents, Friends, and Professionals. New York: Oxford Univ. Press, 1999.

OTHER

"Congenital Myasthenic Syndromes MDA Fact Sheet." <http://www.mdausa.org/disease/fasheet_cms.html>. Muscular Dystrophy (May 6, 2004).

"NINDS Congenital Myasthenia Information Page." National Institute for Neurological Diseases and Stroke. (May 4, 2004). <http://www.ninds.nih.gov/health_and_medical/disorders/congenital_myasthenia.htm>.

ORGANIZATIONS

National Institute for Neurological Diseases and Stroke (NINDS). P.O. Box 5801, Bethesda, MD 20824. (301) 496-5751. (800) 352-9424. <http://www.ninds/nih.gov>.

National Organization for Rare Disorders (NORD). 55 Kenosia Avenue, Danbury, CT 06813-1968. (203) 744-0100 or (800) 999-6673; Fax: (203) 798-2291. [email protected]. <http://www.rarediseases.org>.

Myasthenia Gravis Foundation of America, Inc. 1821 University Ave. W., Suite S256, St. Paul, MN 55104. (651) 917-6256 or (800) 541-5454; Fax: (651) 917-1835. [email protected]. <http://www.myasthenia.org>.

Brian Douglas Hoyle, PhD

Gale Encyclopedia of Neurological Disorders Hoyle, Brian

Congenital Myasthenia

views updated May 21 2018

Congenital myasthenia

Definition Congenital myasthenia is an inherited condition present at birth that interferes with nerve messages to the muscles. Although some symptoms are similar (muscle weakness worsened by use), congenital myasthenia differs from myasthenia gravis , which usually presents in adulthood and is almost always due to an autoimmune disorder rather than an inherited genetic defect.

Description

Most cases of congenital myasthenia are noticeable at or shortly after birth. In rare cases, symptoms don't present themselves until some time later in childhood or in early adult life.

Normal muscle function requires a chemical messenger called acetylcholine (ACh) to travel from the nerve cell to a receptor on the muscle endplate, in order to stimulate muscle contraction and movement. After the ACh has initiated muscle contraction, it is degraded by an enzyme.

In congenital myasthenia, one of three problems occurs with this system:

Too little ACh is produced, or its release from the nerve cell is impaired
The enzyme that should degrade ACh is faulty, resulting in prolonged stimulation of the muscle by excess ACh and ultimately in muscle damage
The area of the muscle that should be stimulated by the presence of ACh (called the endplate receptor) is defective, and therefore the muscle can not be sufficiently stimulated

Demographics

Figures regarding the frequency of congenital myasthenia are not available, but it is considered to be a very rare condition.

Causes and symptoms

Most cases of congenital myasthenia are inherited in a recessive fashion, meaning that a baby has to receive a defective gene from each parent to actually manifest the condition.

Babies with congenital myasthenia are often described as "floppy," with weak muscle tone, droopy eyelids, excessive fatigue , compromised eye movements, facial weakness, feeding problems and delayed developmental milestones (such as holding up head, sitting, crawling). In more severe conditions, the muscles that aid breathing are affected, resulting in respiratory difficulties.

The baseline degree of weakness is exacerbated by any activity, including feeding, crying, or moving. Episodes of more severe symptoms may be precipitated by illness, emotional upset, or fever. Some cases of congenital myasthenia progress over time, so that initially mild symptoms can become more severe as the individual ages.

Diagnosis

The diagnosis of congenital myasthenia will usually be suspected when a careful physical examination reveals muscle weakness that is worsened by use of a particular muscle. Certainly, a family history of congenital myasthenia heightens such a suspicion.

A test called electromyography measures muscle activity after stimulation. When muscle activity decreases with repeated stimulation, congenital myasthenia is suspected. Testing the blood for the presence of specific antibodies can help distinguish between myasthenia gravis and congenital myasthenia. Very specific microelectrode testing of the muscle endplate receptors can help define whether faulty receptors are responsible for the impairment. Genetic testing and muscle biopsy examination are being researched, but are not currently used for routine diagnosis.

Treatment team

Children with congenital myasthenia will usually be treated by a team consisting of a pediatric neurologist , as well as a physical therapist, occupational therapist, and speech and language therapist. If respiratory problems ensue, a pulmonologist and respiratory therapist may need to be consulted.

Treatment

There are no treatments available to cure congenital myasthenia. A number of medications may improve symptoms in children with congenital myasthenia. The specific medication that will be most helpful depends on whether the impairment is due to decreased ACh production and release, impaired enzyme degradation of ACh, or faulty ACh receptors in the muscle endplates. Some of the types of medications available include:

Anticholinesterase medications: Inhibit the degradation of ACh, allowing more to be available to stimulate muscles.
3,4, diaminopyridine: Increases the release of ACh from the nerve cells.
Qunidine or fluoxetine: Prevents overstimulation of ACh receptors on muscle endplates, thus preventing muscles from damage secondary to prolonged stimulation.

Prognosis

The severity of symptoms, responsiveness to medication, and ultimate prognosis varies widely among congenital myasthenia patients.

Resources

BOOKS

"Nutritional Disorders of the Neuromuscular Transmission and of Motor Neurons." In Nelson Textbook of Pediatrics, edited by Richard E. Behrman, et al. Philadelphia: W. B. Saunders Company, 2004.

Rose, Michael, and Robert C. Griggs. "Congenital Myasthenias." In Textbook of Clinical Neurology, edited by Christopher G. Goetz. Philadelphia: W. B. Saunders Company, 2003.