Emery-Dreifuss muscular dystrophy

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Emery-Dreifuss muscular dystrophy is a condition that primarily affects muscles used for movement (skeletal muscles) and the heart (cardiac muscle). Among the earliest features of this disorder are joint deformities called contractures. Contractures restrict the movement of certain joints, most often the elbows, ankles, and neck, and usually become noticeable in early childhood. Most affected individuals also experience muscle weakness and wasting that worsen slowly over time, beginning in muscles of the upper arms and lower legs and later also affecting muscles in the shoulders and hips.

Almost all people with Emery-Dreifuss muscular dystrophy develop heart problems by adulthood. In many cases, these heart problems are abnormalities of the electrical signals that control the heartbeat (cardiac conduction defects) and abnormal heart rhythms (arrhythmias). If untreated, these abnormalities can lead to a sensation of fluttering or pounding in the chest (palpitations), an unusually slow heartbeat (bradycardia), fainting (syncope), heart failure, and an increased risk of sudden death.

Researchers have identified several types of Emery-Dreifuss muscular dystrophy that are distinguished by their pattern of inheritance: X-linked, autosomal dominant, and autosomal recessive. The types usually have similar signs and symptoms, although a small percentage of people with the autosomal dominant form experience heart problems without any weakness or wasting of skeletal muscles.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Mutations in several genes, including EMD, FHL1, and LMNA, can cause Emery-Dreifuss muscular dystrophy. Mutations in the EMD gene or, less commonly, in the FHL1 gene cause the X-linked type of the condition. Mutations in the LMNA gene cause both the autosomal dominant and autosomal recessive types of the condition.

The genes associated with Emery-Dreifuss muscular dystrophy appear to be essential for the normal function of skeletal and cardiac muscle. The EMD and LMNA genes provide instructions for making proteins that are components of the nuclear envelope, which surrounds the nucleus in cells. The nuclear envelope regulates the movement of molecules into and out of the nucleus, and researchers believe it may play a role in regulating the activity of certain genes. The protein produced from the FHL1 gene appears to be involved in other muscle cell functions, including chemical signaling, maintaining the structure of these cells, and influencing muscle growth and size.

Mutations in the EMD, FHL1, and LMNA genes that cause Emery-Dreifuss muscular dystrophy prevent the production of their respective proteins or lead to abnormal or nonfunctional versions of these proteins. Researchers speculate that changes in EMD or LMNA could weaken the structure of the nuclear envelope in cells that undergo a lot of mechanical stress, such as skeletal and cardiac muscle cells, making these cells more fragile. FHL1 gene mutations also alter the structure and function of muscle cells, although little is known about the mechanism. Researchers continue to investigate how genetic changes can lead to the joint contractures, muscle weakness, and heart abnormalities characteristic of Emery-Dreifuss muscular dystrophy.

Changes in several other genes result in conditions that resemble Emery-Dreifuss muscular dystrophy, but with more variable features. Some researchers consider these to be types of Emery-Dreifuss muscular dystrophy, while others believe that they represent similar, but separate, disorders.

In more than half of all cases of Emery-Dreifuss muscular dystrophy, the genetic cause of the condition is unknown. Researchers believe that mutations in additional genes, which have not been identified, can also cause this condition.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Emery-Dreifuss muscular dystrophy can have several different patterns of inheritance. When the condition is caused by mutations in the EMD or FHL1 gene, it is inherited in an X-linked recessive pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. Males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

In females (who have two X chromosomes), a mutation typically must be present in both copies of the gene to cause X-linked Emery-Dreifuss muscular dystrophy. Females who carry one altered copy of the gene usually do not experience the muscle weakness and wasting that are characteristic of this condition. However, some of these female mutation carriers develop heart problems or mild muscle weakness.

In most cases of Emery-Dreifuss muscular dystrophy resulting from mutations in the LMNA gene, this condition has an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. About 65 percent of autosomal dominant Emery-Dreifuss muscular dystrophy cases are caused by new mutations in the LMNA gene and occur in people with no history of the disorder in their family. In the remaining cases, people with this form of the condition inherit the altered LMNA gene from an affected parent.

Rarely, Emery-Dreifuss muscular dystrophy caused by LMNA gene mutations is inherited in an autosomal recessive pattern. Autosomal recessive inheritance means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

The overall prevalence of Emery-Dreifuss muscular dystrophy is unknown. The X-linked type of this disorder affects an estimated 1 in 100,000 people. The prevalence of the autosomal dominant type is unknown, although it appears to be more common than the X-linked type. The autosomal recessive type appears to be very rare; only a few cases have been reported worldwide.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Elevated circulating creatine kinase concentration · Very frequent (99-80%)

The activity of creatine kinase in the blood circulation is above the upper limit of normal.

Joint stiffness · Very frequent (99-80%)

Joint stiffness is a perceived sensation of tightness in a joint or joints when attempting to move them after a period of inactivity. Joint stiffness typically subsides over time.

Limb-girdle muscular dystrophy · Very frequent (99-80%)

Muscular dystrophy affecting the muscles of the limb girdle (the hips and shoulders).

Myopathy · Very frequent (99-80%)

A disorder of muscle unrelated to impairment of innervation or neuromuscular junction.

Myotonia · Very frequent (99-80%)

An involuntary and painless delay in the relaxation of skeletal muscle following contraction or electrical stimulation.

Pectus excavatum · Very frequent (99-80%)

A defect of the chest wall characterized by a depression of the sternum, giving the chest ("pectus") a caved-in ("excavatum") appearance.

Reduced tendon reflexes · Very frequent (99-80%)

A reduction (hyporeflexia) or complete absence (areflexia) of the involuntary muscle contraction normally elicited by a reflex stimulus, such as tapping a deep tendon.

Absent muscle fiber emerin · Frequent (79-30%)

Immunohistochemistry shows complete lack of emerin protein in the muscle biopsy.

Other findings in the same source

From: Orphanet

Additional reported features include Achilles tendon contracture (Frequent (79-30%)); Back pain (Frequent (79-30%)); EMG: myopathic abnormalities (Frequent (79-30%)); Elbow flexion contracture (Frequent (79-30%)); Gait disturbance (Frequent (79-30%)); Hypertriglyceridemia (Frequent (79-30%)); Increased LDL cholesterol concentration (Frequent (79-30%)); Proximal lower limb amyotrophy (Frequent (79-30%)); Proximal muscle weakness in lower limbs (Frequent (79-30%)); Proximal muscle weakness in upper limbs (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Emery-Dreifuss muscular dystrophy is Neurology, with a neurologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which nervous-system findings help explain the symptoms?
• Would an assessment of walking, communication or daily function be helpful?
• Are rehabilitation or other specialist services relevant?

Treatment discussions and follow-up

Where the source describes treatments, these are an overview of possible care, not a prescription for an individual. Ask which option applies to the confirmed diagnosis, what benefit is expected, what adverse effects to watch for and how progress will be assessed. Availability, approvals and local practice can differ from the country described in the source.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.