Multiminicore disease (MmD)

Multiminicore disease (MmD) is a condition that affects the muscles and is part of a group of genetic muscle conditions called congenital myopathies. These conditions are present from birth or in infancy and lead to muscle weakness.

The symptoms and severity of MmD can vary. There are different types depending on the genetic cause. Even with the same genetic cause, symptoms and severity can vary between people.

MmD is named after the appearance of minicores on a muscle biopsy, which are small, unusual areas in muscle fibres that can be seen under a microscope. MmD is also known as minicore myopathy and multiminicore myopathy.

SELENON-related MmD

SELENON-related MmD typically begins at birth or within the first few months of life. It’s known as the ‘classic form’. Children with SELENON-related MmD often have hypotonia (low muscle tone) and weakness in the muscles of the torso and the limbs closest to the torso. They often experience a delay in reaching motor milestones, such as sitting unaided and walking. Most children will learn to walk independently and keep this ability into adulthood. Although weakness usually occurs across all muscles, it can be more severe in the torso and neck areas. Rigid spine (stiffness of the spine), scoliosis (curvature of the spine), and breathing problems are common. Sometimes people can have problems with feeding and a feeding tube may be required.

RYR1-related MmD

RYR1-related MmD is highly variable but has some common features. Muscle weakness is most severe in the muscles closest to the torso. Weakness around the eye (external ophthalmoplegia) can lead to problems with eye movements and sometimes ptosis (droopiness of the eyelids). Some people may have joint laxity, scoliosis, and difficulties with feeding and breathing. These difficulties could be mild but should be monitored.

Severe cases may rarely have an antenatal form, called arthrogryposis multiplex congenita (AMC). This causes contractures (joint stiffness) at birth because of limited movement in the womb. AMC is also linked to physical features like an elongated head, low-set ears, and a short neck. Breathing muscles can be moderately to severely affected, so breathing problems are common.

MYH7-related MmD

MYH7-related MmD causes slowly progressive muscle weakness in the distal muscles, those furthest away from the centre of the body, particularly in the feet and toes. Scoliosis (curvature of the spine), breathing difficulties and heart disease are common. This condition can vary greatly from person to person, even between people within the same family. Some people with MYH7-related MmD may have little or no muscle weakness at all.

TTN-related MmD

TTN-related MmD causes slowly progressive muscle weakness from birth. Common features include scoliosis, rigid spine, contractures and weakness of the breathing and heart muscles.

Genetic changes

MmD is caused by changes in genes that are important for muscle function. Most cases are due to changes in the SELENON gene or RYR1 gene. In some rarer cases, changes in the MYH7 or TTN genes can also cause MmD.

Changes in these genes all cause muscle weakness in different ways. Changes in the SELENON gene affect the structure of muscle fibres and the body’s ability to defend against oxidative stress. Changes in the RYR1 gene disrupt the muscles’ ability to contract and relax. These changes in the genes lead to the development of MmD and muscle weakness.

Changes in the RYR1 gene can cause a condition known as malignant hyperthermia. This a potentially life-threatening reaction to certain anaesthetics or muscle relaxants.

Inheritance

Most forms of MmD are inherited in an autosomal recessive pattern, where both parents need to pass down a changed gene to cause the condition. Only MYH7-related MmD is inherited in an autosomal dominant pattern, where only one changed gene (from one parent) can cause the condition. Rarely, a genetic change can occur where there is no family history of the condition.

For more information, see our inheritance and genetics page.

A GP can refer a child to a paediatrician to investigate symptoms. A paediatrician is a doctor who specialises in treating babies, children, and young people. If needed, the paediatrician can then refer the child to a neurologist, a doctor that specialises in conditions affecting the muscles and nervous system.

The neurologist will carry out a physical assessment and may recommend further tests, such as a muscle MRI, muscle biopsy, with genetic testing, to come to a diagnosis.

In a muscle biopsy, a small sample of muscle is taken and examined under a microscope. Usually, muscle tissue has two types of fibres, type 1 and type 2, in roughly equal amounts. People with MmD will have more type 1 fibres, and there are minicore structures (multiple short-length core lesions) within these fibres.

Genetic testing, using a blood sample, can identify the specific gene change and confirm the diagnosis. As genetic testing becomes more advanced, some people with muscle weakness may receive a diagnosis without needing a muscle biopsy. Instead, they may be given a diagnosis based on an identified gene change, such as RYR1-related myopathy or SELENON-related myopathy.

Once the gene change has been identified in one affected family member, it’s possible to use this sequence to diagnose other family members and unaffected carriers.

For more information, see our diagnosis page.

A multi-disciplinary approach is important in not only managing the condition and symptoms but in improving wellbeing too. This involves different healthcare professionals working together.

Access to a healthcare team

People with MmD should have access to a multidisciplinary healthcare team. The lead professional will usually be a neurologist. If you do not have contact with a neurologist or specialist doctor, speak to your GP about getting access.

Exercise and physiotherapy

Physiotherapy and mild exercise are encouraged to maintain muscle strength and mobility. It can also maintain breathing capacity and slow the progression of contractures (joint stiffness) or scoliosis (curvature of the spine). A physiotherapist is a healthcare professional who helps manage symptoms through movement, exercise, and manual therapy. They can put together a suitable exercise plan to follow. Recommended exercises include swimming, walking, and pedalling, as these aerobic exercises can help maintain a healthy cardiovascular system and a steady weight. To find out more about advice for adults, see exercising with a muscle wasting condition.

Orthopaedics

Orthopaedic management may be needed to manage joint contractures or scoliosis. The type of orthopaedic management will depend on the person’s particular needs. This can include using splints, braces, and other tailored orthotic devices. Surgery may also be needed.

Respiratory

Respiratory weakness is common with MmD, particularly for people with SELENON-related MmD. Respiratory function and lung capacity should be monitored at regular checkups. Annual flu vaccinations should also be taken to help prevent chest infections. Overnight sleep studies are often used to assess breathing while sleeping and diagnose night-time breathing problems. This is usually in the form of nocturnal hypoventilation, where low oxygen levels and high carbon dioxide levels can cause symptoms of morning headaches and daytime fatigue. Nocturnal hypoventilation can be treated using non-invasive ventilation (NIV) during sleep to help maintain adequate ventilation. This should be discussed with a specialist.

Cardiac

Some people with MmD could develop cardiomyopathy (heart disease), particularly in those with changes in the RYR1, MYH7, and TTN genes. Cardiac function should be regularly monitored in these cases. Monitoring will include an electrocardiogram (ECG), echocardiogram (cardiac ultrasound), and Holter monitors.

Anaesthesia stops a person feeling pain during a procedure or surgery. Before any medical procedure, it’s important to make the anaesthetist and other healthcare professionals aware of a diagnosed muscle wasting condition, as well as any heart or breathing complications. This will help them plan for specific needs and ensure safety. Those with a change in the RYR1 gene are at particularly high risk of a severe reaction known as malignant hyperthermia.

Malignant hyperthermia

Malignant hyperthermia (MH) is a potentially life-threatening reaction, triggered by the use of certain general anaesthetics and muscle relaxants. Conditions with changes in the RYR1 gene increase a person’s risk of developing MH.

Symptoms of MH include a rapid rise in body temperature, rigidity of muscles or spasms, rapid heart rate (tachycardia), muscle breakdown (rhabdomyolysis), and dark brown urine due to broken down muscle entering the bloodstream and urine (myoglobinuria). MH must be treated immediately with a drug called Dantrolene, whilst also attempting to cool the person’s body temperature.

MH can be prevented by avoiding triggering anaesthetic agents and using alternative drugs. Suxamethonium (succinylcholine) must be avoided. It’s crucial that the clinical team is made aware of the condition if surgery under general anaesthetics is needed, so that alternative options can be considered.