About emery-dreifuss syndrome

What is emery-dreifuss syndrome?

Emery-Dreifuss muscular dystrophy (EDMD) is a rare, often slowly progressive genetic disorder affecting the muscles of the arms, legs, face, neck, spine and heart. The disorder consists of the clinical triad of weakness and degeneration (atrophy) of certain muscles, joints that are fixed in a flexed or extended position (contractures), and abnormalities affecting the heart (cardiomyopathy). Major symptoms may include muscle wasting and weakness particularly in arms and lower legs (humeroperoneal regions) and contractures of the elbows, Achilles tendons, and upper back muscles. In some cases, additional abnormalities may be present. In most cases, EDMD is inherited as an X-linked or autosomal dominant disease. In extremely rare cases, autosomal recessive inheritance has been reported. Although EDMD has different modes of inheritance, the symptoms are nearly the same.

EDMD belongs to a group of rare genetic muscle disorders known as the muscular dystrophies. These disorders are characterized by weakness and atrophy of various voluntary muscles of the body. Approximately 30 different disorders make up the muscular dystrophies. The disorders affect different muscles and have different ages of onset, severity and inheritance patterns.

What are the symptoms for emery-dreifuss syndrome?

The age of onset, severity, and progression of EDMD varies greatly from case to case, even among individuals of the same family. Some affected individuals may experience childhood onset with rapid disease progression and severe complications; others may experience adult onset and a slowly progressive course.

EDMD is associated with the clinical triad of contractures, muscle Weakness, and heart disease. A contracture occurs when thickening and shortening of tissue causes deformity and restricts movement of affected areas, especially the joints. The elbows and Achilles tendons are the most common sites for contractures. Contractures are often the first sign in X-linked EDMD and may occur early during childhood. In autosomal dominant EDMD contractures usually develop after the onset of muscle Weakness.

Progressive muscle Weakness and degeneration (atrophy) usually develops during late childhood or early adolescence usually in the upper arms and lower legs (humero-peroneal regions). Weakness and atrophy of legs muscles may cause affected children to walk on their toes and may result in an abnormal waddling gait. Muscle Weakness affecting the arms may cause various problems such as difficulty in raising the arms above the head.

Eventually, the muscles of the thigh and hips may become involved making it difficult to climb stairs. The neck, shoulder girdle, and forearms may eventually become involved and the spine may become rigid. As affected individuals age, they may experience limited mobility of the neck. Mild Weakness of facial muscles has also been reported. Abnormal curvature of spine (scoliosis) may also occur.

Muscle Weakness and atrophy is usually slowly progressive during the first three decades of life. Eventually, it may become more rapid. Some individuals with autosomal dominant EDMD may eventually lose the ability to walk (ambulate) and require a wheelchair. Loss of ambulation is rare in X-linked EDMD.

Heart abnormalities are the third prominent feature of EDMD and may result in serious complications. Although onset can vary, heart abnormalities usually develop after the second decade of life. Affected individuals may develop disease of the heart muscles (cardiomyopathy) potentially resulting in Palpitations, Fatigue, poor exercise tolerance, and an impaired ability of the heart to pump blood. Some individuals may experience conduction defects resulting in Irregular heartbeats (arrhythmias) or heart block.

Heart block is characterized by interference with the transfer of the electrical nerve impulses (conduction) that regulate the normal, rhythmic, pumping action of the heart muscle. The normal heart has four chambers. The two upper chambers are the atria and the two lower chambers are the ventricles. Within the right atrium of a normal heart is a natural pacemaker that initiates and controls the heartbeat. The electrical stimulus travels from the pacemaker (sinoatrial or SA node) to the ventricles along a very specific path consisting of conducting tissue and known as the AV (atrioventricular) node. As long as the electrical impulse is transmitted normally, the heart behaves normally. If the transmission of the signal is impeded, the blocked transmission is known as a heart block or an AV block.

Heart blocks are categorized according to the degree of impairment. The severity of such conduction abnormalities varies among individuals with EDMD. In the mild form of heart block, the two upper chambers of the heart (atria) beat normally, but the contractions of the two lower chambers (ventricles) lag slightly behind. In the more severe forms, only a half to a quarter of the atrial beats are conducted to the ventricles. In complete heart block, the atria and ventricles beat separately. In some cases, heart block may lead to outs (syncope), breathlessness, and/or Irregular heartbeats (arrhythmias). In severe cases, sudden death is possible.

What are the causes for emery-dreifuss syndrome?

In most cases, EDMD is inherited as an X-linked recessive trait. EDMD may also be inherited as an autosomal dominant trait. Autosomal recessive inheritance is extremely rare, but has been reported in at least one family. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome Xq28” refers to band 28 on the long arm of the X chromosome. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

X-linked genetic disorders are conditions caused by an abnormal gene on the X chromosome and manifest mostly in males. Females that have a defective gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms because females have two X chromosomes and only one carries the defective gene. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains a defective gene he will develop the disease.

Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son.

If a male with an X-linked disorder is able to reproduce, he will pass the defective gene to all of his daughters who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring.

Investigators have determined that the X-linked form of EDMD is caused by disruption or changes (mutations) of the EMD (also known as STA) gene located on the long arm of the X chromosome (Xq28). The EMD gene encodes a muscle protein known as emerin. Emerin is found in most cell types of the body and skeletal and cardiac muscle have particularly high expression levels.

Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy. The risk is the same for males and females.

Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

All individuals typically carry a number of abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Investigators have determined that the autosomal dominant and autosomal recessive forms of EDMD are caused by mutations of the same gene located on the long arm of the chromosome 1 (1q21.2). The gene is known as the LMNA gene and encodes the proteins lamin A and lamin C. Interestingly, mutations in this gene also cause a variety of other human diseases, including limb-girdle muscular dystrophy, dilated cardiomyopathy, Dunnigan-type familial partial lipodystrophy, and the premature aging disease Hutchinson-Gilford progeria syndrome.

EDMD can also result from mutations in the nuclear envelope proteins nesprin-1 and -2, which also directly interact with emerin. Mutations in the SUN-domain proteins SUN1 and SUN2, which form a complex with nesprins to connect the nucleus to the cytoskeleton, can also cause EDMD. These findings suggest that disruption in the LINC (Linker between nucleoskeleton and cytoskeleton) complex can contribute to the muscular phenotype in EDMD.

Lastly, some cases of EDMD have been attributed to mutations in the FHL1 gene, also known as LUMA,  a nuclear membrane protein that binds to emerin   At the same time, more than half of all EDMD patients have no identifiable mutations in the above genes, suggesting that additional genes/mutations must be responsible for EDMD.  Consequently, substantial efforts are underway to identify additional genes that cause EDMD and the underlying disease mechanism.

What are the treatments for emery-dreifuss syndrome?

No specific treatment exists for EDMD. Treatment is aimed at the specific symptoms present in each individual. Treatment options may include physical therapy and active and passive exercise to build muscle strength and prevent contractures. Surgery may be recommended in some cases to treat contractures or scoliosis. The use of mechanical aids (e.g., canes, braces, and wheelchairs) may become necessary to aid walking (ambulation).

Clinical Testing and Work-Up

Children diagnosed with EDMD should be monitored regularly for potential heart involvement. In the case of serious heart involvement, cardiac pacemakers may be implanted and treatment with antiarrhythmic drugs may become necessary.

Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.

What are the risk factors for emery-dreifuss syndrome?

Emery-Dreifuss muscular dystrophy (EDMD) or emery-dreifuss syndrome is a rare, often slowly progressive genetic disorder affecting the skeletal and cardiac muscles that make up the arms, legs, face, neck, spine, and heart.

The following can determine your susceptibility to EDMD:

  • Age: Rarely does EDMD start before age five, with the average onset age falling between five and ten years.
  • Genetic mutations: Emery-Dreifuss muscular dystrophy can result from mutations in a number of genes, such as EMD and LMNA, which are necessary for the healthy operation of the skeletal and cardiac muscles.
  • Inheritance: If there were indications of positive X-linked or autosomal dominant traits in your family history, they might have been passed down to the next generation, becoming the cause of EDMD.
  • In a small percentage of cases, risk factors include a family history of autosomal dominant and recessive disorders.
  • Avoid: Obesity and depolarizing muscle relaxants like succinylcholine and volatile anesthetics like halothane and isoflurane are triggers for malignant hyperthermia.
  • Slowly progressive muscle weakness and wasting at an early age of childhood.
  • Humeroperoneal muscle wasting.
  • Joint contractures begin in early childhood.
  • Above are the most common risk factors for Emery-Dreifuss muscular dystrophy (EDMD). If you experience pain in the skeletal and cardiac muscles, keep an eye on the aforementioned factors and see a doctor.
A sensation of fluttering or pounding in the chest (palpitations),An unusually slow heartbeat (bradycardia),Fainting (syncope),Heart failure,An increased risk of sudden death

Heart problems by adulthood, they might even have heart issues without any skeletal muscle wasting or weakness.

Antiarrhythmic drugs

Is there a cure/medications for emery-dreifuss syndrome?

Emery-Dreifuss muscular dystrophy (EDMD) occurs in the muscles and affects the movement of the body and also the heart. Contractures take place in this disorder wherein joint deformities happen in your body. •These contractures present in the body restrict body movements significantly. •The restrictions most often affect the elbows, ankles, and neck. •These deformities are usually noticed in early childhood. Almost every person with EDMD also develops heart problems by the time they reach adulthood. •There doesn’t seem to be any specific treatment for emery dreifuss syndrome that would help cure the syndrome entirely. •But there are certain treatments one can try which will improve your muscle movements up to a degree and can help ease complications. •The heart-related difficulties can be treated with medications and treatments such as Antiarrhythmics, Beta-blockers, ACE inhibitors, Pacemakers, Defibrillators, and Heart transplantations. •Breathing problems can be treated with Physical therapy, Mechanical ventilation. •Contractures and Scoliosis can be treated with orthopedic surgery. •For mobility improvement, try Physical therapy, Occupational therapy, and Mechanical aids. •These are some of the treatment methods and medications a patient suffering from Emery-Dreifuss Muscular Dystrophy should try. •Aggressive support and care are to be provided to the patient to prolong life expectancy. •The primary and most important concern should be avoiding sudden cardiac death.

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