Introduction

Overview of Emery-Dreifuss Muscular Dystrophy (EDMD)

Emery-Dreifuss Muscular Dystrophy (EDMD) is a genetic condition (inherited/passed down from family members).¹ The condition was named after Dr. Ian Emery and Dr. Fritz Dreifuss, who first discovered the disorder in 1966.² Emery-Dreifuss is one of nine types of muscular dystrophy. Muscular dystrophy is a condition that causes muscle weakness,³ affecting primarily voluntary muscles (typically the shoulders, arms and legs).² The symptoms of EDMD tend to start to developing during childhood or the adolescent years,³ therefore, the need for recognition of early signs that could indicate EDMD are vital for early diagnosis and management of the condition.

What is EDMD?

According to the Centres for Disease Control and Prevention (CDC), Emery-Dreifuss is a rare type of muscular dystrophy that affects approximately 1 in 100,000 individuals.⁴ It is characterised by its early onset of symptoms within an individual's first decade of life, which become more apparent during puberty and adolescence.⁵

How EDMD differs from other muscular dystrophies

EDMD differs from other muscular dystrophies due to its specific clinical symptoms including early in life slow progressive muscle weakness, joint contractures and stiffness,life-threatening cardiac complications such as atrial block (the heart's electrical signals are impaired³), heart palpitations, cardiomyopathy (walls of the heart become thickened or stiff )⁶ and heart failure.^3,5

Other muscular dystrophies such as Duchenne Muscular Dystrophy (DMD) tend to show a rapid onset of symptoms and more variability within symptoms, with periods of rapid muscle deteoriation.⁷ However, EDMD has a distinct progressive pattern of early-onset symptoms and underlying genetic causes, along with distinct complications of the heart which are generally not exhibited in the other eight types of muscular dystrophy.⁸

Genetic causes 

EDMD is caused by mutations in genes called EMD, LMNA and FHL1.⁵ These genes produce proteins in the body that surround the nucleus of all muscle cells, known as the ‘nuclear envelope’.⁵ These mutations result in defects in muscle differentiation and function, resulting in early onset joint contractions, stiffness and progressive muscle weakness.¹⁰

Inheritance patterns

EDMD can be inherited in three ways; a sex-linked trait, a autosomal dominant trait or a autosomal recessive trait.^3,12 On the rare occasion, sometimes there is no family history of EDMD, but one individual in the family has been affected.^3,8 This is likely due to a new EDMD-linked mutation in the affected individual, which can then be passed on to their offspring.^3,8

Sex-linked inheritance

In human chromosomal sex determination, males present an XY combination, where they have one X chromosome (inherited from the mother) and one Y chromosome (inherited from the father).¹¹ Females present a XX combination, where they have inherited one X chromosome from each parent.¹¹

EDMD can be inherited as a sex-linked (X-linked; the genetic mutation is present on the X chromosome) trait.^3,8 This means that this inheritance pattern typically only affects males, but it can be carried by females who are unaffected by the genetic condition.^3,8 A man with EDMD cannot pass the condition to his male children (as they inherited his Y chromosome), but any female children will inherit the affected X chromosome and become carriers of the genetic mutation.^3,8 These females can pass this trait onto their own children.^3,8

Autosomal dominant inheritance

EDMD can be inherited as an autosomal dominant trait (only one parent needs to have the mutation to pass it on), which can affect bothmales and females.^3,8 Each child of an affected EDMD parent has a 50% chance of becoming affected, and a 50% chance of being unaffected.^3,8

Autosomal recessive inheritance

EDMD can be inherited as an autosomal recessive trait, where both parents are unaffected but they carry the genetic mutation.³ This results in a 1 in 4 (25%) chance of their future children inheriting the genetic mutation for EDMD.³

Early signs and symptoms

Joint contractures

Joint contractures are the permanent tightening of muscles, tendons and connective tissue around a joint.¹³ This causes the joints to shorten and permanently restricts movement of the affected joints.^3,14 Joint contractures develop very early on in EDMD and are typically the first sign of the condition during childhood, contrary to other muscular dystrophy types.^8,14 Joint contractures become apparent before the onset of progressive muscle weakness.¹⁰ The commonly affected joints include:¹⁰

• Elbows - causing the arms to be bent in a semi-flexed way which results in limited movement and bending, and the loss of the ability to straighten the elbows³
• Ankles/Achilles tendons - causing an individual to walk on their toes due to tightness across the ankles³ and the shortening of the Achilles tendon¹⁵
• Neck/spine - limited neck rotational movements which can result in the limited movement of the spine^2,10

Joint contractures are one of the first clinical indicators of EDMD, and they can have a significant impact on performing daily activities (such as walking, eating, standing for long periods of time and getting dressed) and overall quality of life.¹⁶ Joint contractures can have further consequences, as some individuals may experience swallowing problems as a result of limited spinal movement (a rigid spine), and the permanent alteration of neck structures, along with weakness of the respiratory muscles, which risks respiratory failure.¹⁷

Joint stiffness

Joint stiffness in EDMD can develop before early-onset joint contractures, meaning that the individual may experience regular stiff joints before the permanent effects and development of fixed contractures set in.¹⁰ Joint stiffness is being unable to move the joint freely, resulting in reduced mobility, tightness around the joints, and difficulties walking or stretching joints.¹⁰ 

Importance of early signs

Early identification of joint stiffness and contractures by healthcare providers is vital, as adoption of appropriate physiotherapeutic approaches can minimise the progression and severity of both symptoms.² The early and quick progression of EDMD (as symptoms typically develop around 10 years of age)¹⁸, especially joint stiffness and contractures, are early indicators of the following and more severe symptoms of the condition: progressive muscle weakness and cardiac complications.⁸ Understanding the early signs and symptoms of EDMD can enable the appropriate diagnosis of EDMD and the implementation of an appropriate treatment plan to manage symptoms and condition progression.⁸

Diagnosis

EDMD diagnosis involves various methods:

• Understanding of family history
• Physical examination - for joint stiffness and contractures to assess the range of joint movement³
• Blood tests - can reveal high levels of creatine kinase, an enzyme that is associated with muscle damage, but cannot solely confirm EDMD¹⁴
• Molecular genetic testing - to identify the EDMD genetic mutations within DNA¹⁰
• Surgical removal and biopsy of affected muscular tissue³
• Electromyography - an electrical test to assess the health of the muscles and nerves¹⁴

Healthcare professionals assess joint contractures and stiffness through two range of motion (ROM) tests, using a goniometer.¹⁹ A goniometer uses a stationary arm to measure joint angles from the axis of the joint, is regularly used in physiotherapy.¹⁹ The ROM tests are:

• Active range of motion (AROM) -  Performed by the individual (can voluntarily move the body part). This ROM is achieved when opposing muscles contract and relax to produce the joint movement, and can also assess muscle weakness¹⁹
• Passive range of motion (PROM) - The joint is moved using an outside force (e.g., a healthcare practitioner)¹⁹

Management approaches

There is no cure for EDMD, however, symptoms can be managed to slow disease progression and improve quality of life, using multi-disciplinary care.³

Physiotherapy

Performing stretching and range of motion (ROM) exercises can help slow the development of joint stiffness and permanent contractures, and aid in joint flexibility.²⁰ Additionally, regular gentle exercise such as walking can aid in maintaining muscle strength to prevent worsening of contractures.³ Maintaining a healthy weight and eating a balanced diet will help to minimise the stress on weakened muscles.³

Occupational therapy & surgery

Occupational therapists can help individuals with EDMD adapt their daily activities to aid in the loss of muscle strength.²⁰ This could involve the use of mechanical aids such as canes, ankle and foot braces to aid in walking, or wheelchairs to help with mobility and independence.²⁰ Occupational therapists may also recommend certain home modifications, such as dressing aids and communication devices, to aid in daily activities.²⁰ Surgery may be offered to treat joint contractures (to divide the heel tendons to help with walking) and scoliosis (abnormal twisting of the spine).³

Cardiac monitoring

It is recommended that individuals with EDMD, and their families, undergo genetic counselling to allow for further understanding of the disease-causing mutations and to implement preventative measures for family members in the future.¹⁷ It is also recommended that individuals with EDMD receive yearly cardiac check-ups with a cardiologist to monitor and test the condition of the heart.⁸ Individuals with EDMD experiencing heart problems may have a pacemaker inserted to help maintain a regular heartbeat.³

Summary

Emery-Dreifuss Muscular Dystrophy (EDMD) is a rare genetic condition that can cause muscle weakness, joint stiffness, contractures and cardiac complications. symptoms of EDMD develop early, during childhood/adolescence, and include joint contractures and stiffness, which are known clinical indicators of EDMD. Joint contractures are the permanent tightening of muscles, tendons and connective tissue around a joint, which permanently restricts movement. Joint stiffness develops before contractures, resulting in reduced mobility. 

Recognising these early clinical signs of EDMD can enable the appropriate diagnosis (via physical examination and genetic testing, for example) and treatment plan to manage symptoms and disease progression. Treatment involves multi-disciplinary care involving physiotherapy, occupational therapy, cardiac care and potential surgery to treat joint contractures. If you are experiencing any of the mentioned symptoms, it is recommended to reach out to your healthcare provider.