Introduction

Central core disease is a rare neuromuscular disorder that belongs to a group of diseases called congenital myopathies. Like many congenital myopathies, central core disease is characterised by muscle weakness (myopathy) and low muscle tone (hypotonia).¹ If you have central core disease, parts of your skeletal system may also be affected; consequently, you might develop scoliosis or have a dislocated hip. 

The parts of your body usually affected are the proximal parts. These are the regions which are the closest to the centre of your body, including:

• Upper arms 
• Upper legs
• Pelvis 
• Shoulders 

The severity of the disease varies from person to person and ranges from mild to severe. However, it is generally not fatal.²

What causes central core disease? 

Central core disease is an inherited congenital disease. It is caused by a genetic mutation in one of the genes that help to control the way your muscles function. The term ‘congenital’ means that the disease is present at birth, and it is mainly either during infancy or childhood when people are diagnosed. Despite this, some people will have no symptoms until adolescence or adulthood. 

In the majority of cases, central core disease is inherited in an autosomal dominant manner. This means that a single copy of the mutated gene (passed down from one affected parent) is enough to cause the condition.³ 

Mutations in the RYR1 or ryanodine receptor type 1 gene are most commonly associated with central core disease. This gene plays a key role in controlling skeletal muscle contractions by regulating the release of calcium into muscle cells. When movement or quick reactions are needed, calcium release into muscle cells increases and signals to the muscle fibres (myofibrils) to contract, thus allowing movement to occur. 

When a mutation in the RYR1 gene occurs, this regulated calcium release becomes continuous rather than controlled.  As a result, the myofibrils, which are responsible for causing muscle contraction, are disrupted, leading to:⁴ 

• Muscle weakness
• Reduced muscle tone (hypotonia)
• Skeletal abnormalities such as scoliosis or hip dislocation

How to know if you have it

If you suspect that you or someone you know  may have  central core disease, please look out for any of the following symptoms, which range from mild to severe:

• Before birth: observing a decrease or absence in foetal movements
• After birth: observing an abnormal floppiness of the body, particularly the arms and legs
• Muscle weakness: such as difficulties lifting objects, rising from a chair, or climbing stairs 
• Delays in motor milestones such as crawling or walking⁵
• Muscle stiffness:  muscles that seem too tight or don’t move as freely as they should
• Inability to fully close the eyes or ‘bury’ their eyelashes
• Hip dislocation, especially at an abnormally young age
• Abnormal-looking feet or walk, which might be from a tight Achilles tendon 
• Breathing difficulties⁶

If any of these presentations are apparent, you should consult your doctor. From there, physical examinations and specialised diagnostic tests can be arranged to confirm or rule out the presence of central core disease.

Diagnostic tests

Coming to a diagnosis for central core disease involves a variety of factors, with the main ones being:

• Clinical presentation
• Muscle biopsy results
• Genome (all the genes in your body) sequencing for genetic testing
• Imaging tests such as an MRI scan

Clinical presentation 

This is usually the first step to a diagnosis. Your General Practitioner (GP) or family doctor will refer your child to a paediatrician, who is a doctor who specialises in treating babies, children and young people. If needed, or if you’re older, you will be referred to a neurologist, who is a specialist doctor in muscles and the nervous system. Your doctor will do a physical exam to check for the classical symptoms and to identify any specific nerves and muscles that are affected.¹

Muscle biopsy

As part of further testing, you may be required to give a muscle biopsy ( a sample of your muscle tissue) to be analysed in the lab. People with central core disease have abnormal-looking cores in the centre of their type 1 muscle cells, hence the disease name (see picture below). ⁷ This abnormality is caused by the lack of metabolic activity involved in producing energy for the muscle fibres to work. 

Some people may have a few abnormal central cores, and some may have many. However, the number of abnormalities present does not necessarily correlate with the severity of the disease. The muscle biopsy may also show abnormal myofibrils and increased or larger nuclei. These will help confirm your diagnosis.⁸

This is a biopsy of a person with central core disease. The arrows show the central cores on type 1 muscle fibres. Some cells have more than one core, and some aren’t centrally located.

Muscle MRI imaging

Your doctor may also request an MRI scan of one of your limbs to look for any abnormalities present on your muscle tissue. If you have central core disease, your muscle MRI will show up with low signal intensity, which means places which should usually look bright look dark (see picture below). This is associated with an increase in the amount of fat and connective tissue present where skeletal muscle should be, which is characteristic of central core disease.⁹

These are two MRI scans of the thigh of an eleven (A) and a thirteen-year-old (B) year old boy, with the dark parts marked up. Obtained from here

Genetic testing

Testing for the RYR1 gene mutation is a new and upcoming diagnostic method. It is still quite costly, but next-generation sequencing (NGS) is allowing genetic testing to become more accessible and more cost-effective.⁶

Typically, you will submit a sample of your blood or saliva, which will be used to sequence your genes. This can be analysed to indirectly identify the mutation present in the RYR1 gene. 

Alternatively, next-generation sequencing provides a direct method of screening for mutations. In some cases, this method may remove the need for a biopsy, making it a faster and more efficient diagnostic method.¹⁰

Look out for malignant hyperthermia!

This is particularly important if you or your child needs surgery to manage any joint problems or scoliosis. The same RYR1 gene responsible for central core disease is also linked to malignant hyperthermia - a severe reaction, usually to anaesthesia or other medication.¹¹ This means it is highly likely that you or your child may also have malignant hyperthermia. 

 In malignant hyperthermia, common symptoms include:

• Muscle swelling and rigidity
• Increased temperature
• Rhabdomyolysis (rapid muscle breakdown and release of contents into the blood, often life-threatening)⁸ 

As many people with central core disease carry the malignant hyperthermia trait, they are considered high-risk individuals. If you don’t know or have not been tested for malignant hyperthermia susceptibility, then you can ask your doctor for an in vitro contracture test (IVCT) to be done, which will confirm or deny your susceptibility.¹ 

FAQs

Who usually gets central core disease?

Central core disease equally affects everyone, regardless of all genders, in similar proportions. Since it is such a rare disease, the exact number of people per percentage of the population is not known. It is more commonly grouped as part of congenital myopathies, of which it is the most common, occurring in 6 of every 100,000 births.^1,5

What is my outcome after being diagnosed with central core disease?

Central core disease may reduce your quality of life, but it will not cause death unless in severe cases. With the right medical care, most people can manage their symptoms effectively. Ongoing management typically involves:

• Regular check-ups with a neurologist or specialist doctor
• Physiotherapy to maintain muscle strength and mobility
• Potential consultation with an orthopaedic or spine specialist in the event of skeletal problems^1,6

Summary

Central Core Disease is the most common congenital myopathy, characterised by the abnormal central cores seen on biopsies. Individuals diagnosed typically present with muscle weakness and low muscle tone in their proximal muscles. They may also experience hip dislocation and scoliosis as a result. Diagnostic tests are typically biopsies of muscle tissue, an MRI scan of the limbs and the evaluation of any clinical presentations. A newer and arguably more effective diagnostic test can now look directly for changes in the RYR1 gene that cause central core disease. This type of genetic testing is becoming more common in places where the technology is available.