Overview

Centronuclear myopathy (sen-tro-noo-clee-yar ma-yo-path-ee) is an umbrella term that describes different myopathies or diseases of the muscle. If you have it, the nuclei (the central part of your cells) in your muscle tissue are no longer on the edge of your muscle tissue. Instead, they are in the centre, which makes the muscle able to work properly.¹ It is hereditary, and you cannot infect another person with it. Centronuclear myopathy usually happens in younger people, from and is usually diagnosed between birth and early adolescence. However, there are cases where it can happen between adolescence and any time in adulthood.²

Clinical features- know your symptoms

If you think you or someone you know has centronuclear myopathy, your first step is to see a doctor. Part of your diagnosis will be formed by understanding your medical history. If you have any of the following, you may be referred for further tests:

• Weak muscles
• Difficulty breathing or swallowing
• Limp muscles/low muscle tone
• Facial weakness(finding it difficult to smile or make other facial expressions)
• Delayed motor milestones, such as failing to crawl or walk by a certain age⁴

Clinical features-next stage testing

If your doctor suspects you have centronuclear myopathy, they will refer you for various diagnostic tests. You may have to give a muscle biopsy, which is a sample of muscle tissue taken from one of your limbs, to have a look at your muscle fibres under a microscope. Normal muscles will have the nucleus at the edges of the cells. With centronuclear myopathy, the nucleus of a cell will be in the middle¹ (see the blue dots in the picture below).

You might take a muscle MRI scan, which will show what is happening in different tissues. Typically, with hereditary or congenital myopathies, fat tissue replaces muscle tissue. The patterns of this process can help narrow down the type of myopathy you may have.⁵ Similarly, you can take an electromyography, which measures the electrical activity of nerves in your muscles.⁶ Targeting weak muscles especially shows patterns of less activity than normal muscles and short duration, low amplitude measurements (see the picture below).

Most notably, recent developments have allowed the use of genetic testing by using a blood sample to sequence or produce your genome, which is an alphanumeric way to display all the genes that make up your body. This can then be analysed to find the specific gene mutation that is causing your centronuclear myopathy.⁷

Clinical features: know your type

Currently, there are three different types of centronuclear myopathy, varying by the type of gene involved in causing it. You might have myotubular (maa-yo-too-boo-lar) myopathy, autosomal (ot-zom-ol) dominant and autosomal recessive myopathy.¹ Scientists believe that at least 30% of centronuclear myopathies go undiagnosed because they haven’t yet identified the newer disease-causing genes, so there is a scope of research and development to be done.⁸

Myotubular myopathy-The X-linked recessive one

This type of centronuclear myopathy is regarded as the most severe. It usually happens in persons assigned male at birth, and can be identified even in the womb. If your baby has myotubular myopathy, you or your doctor might notice that they aren’t moving around nearly enough in your womb. Your baby will also have polyhydramnios, which is when they are surrounded by too much amniotic fluid in your womb.²

After birth, your baby may show hypotonia, whereby their limbs seem to be floppy, because their muscles lack strength and resistance. They might also have respiratory insufficiency, where your baby’s body isn’t delivering enough oxygen to its body or removing enough carbon dioxide. This might manifest as shortness of breath, rapid breathing, and bluish lips, skin and fingernails.⁸

Other clinical symptoms that you or the healthcare professionals taking care of your baby in the hospital include:

• Macrosomia
• Pyloric stenosis
• Inguinal hernias
• Cryptorchidism⁹

Because of how severe myotubular myopathy is, many babies die during the first year of life from respiratory insufficiency or aspiration pneumonia. Very few people grow to become adolescents, and even fewer reach adulthood. However, they need medical assistance, particularly needing a ventilator for breathing and a gastric tube for feeding.²

As for people assigned female at birth, they don’t have myotubular myopathy, but may carry the gene for it. People who do are called ‘female carriers, and usually live their lives either without any symptoms or with a mildly deteriorating weakness in their arms and legs and reduced facial expressions.⁸

Autosome-linked myopathies

Autosome-linked myopathies are caused by a mutation in a single gene. This gene can either be autosomal dominant, which is inherited from one parent, or autosomal recessive, which is when the gene has been inherited from the genes of both parents.¹

The most common gene related to centronuclear neuropathy cases is the DNM2 gene, accounting for over 50% of cases. It usually manifests during adolescence and adulthood in a mild form or severely in infants. Adolescents and adults may have had delayed motor milestones such as walking, running and climbing stairs ^2. They may also have muscle weakness. A notable form is droopy eyelids or ptosis, and eye muscle-paralysis, or ophthalmoplegia. Children have a more diverse range of clinical symptoms, including:

• Facial weakness to the point that their mouths are hanging open
• Droopy eyelids
• Eye-muscle paralysis, scoliosis
• Very small, weak calves and palms
• A shortened Achilles tendon, which restricts movement and causes pain¹⁰

The most common autosomal recessive gene mutation is in the BIN1 gene, which occurs in adolescents and young adults. The clinical symptoms are similar to DNM2, including their variation between severe to moderate symptoms. The notable difference is in the type 1 muscle fibres or slow-twitch fibres, where the mutation occurs.¹

FAQs

How common is centronuclear myopathy?

Centronuclear myopathy is an incredibly rare disease for which the true number of people who are living with it is unknown. A review article estimated centronuclear myopathy to be 0.08 per 100,000 of the population.¹¹ Specifically, myotubular myopathy has been estimated to affect one in every fifty thousand people assigned male at birth.¹ Due to how rare the disease is, there is very little awareness, understanding and research on it. Some studies estimate that even with our current knowledge, at least 30% of centronuclear myopathies go undiagnosed, owing to a lack of knowledge of all the different genes that might cause it. ⁸

Can people assigned female at birth have myotubular myopathy?

No, people assigned female at birth can only carry the gene for myotubular myopathy, which can then be transmitted to the child they birth. This is because myotubular myopathy happens because of a defect in the activation of genes on the X chromosome. Since people assigned female at birth have two X chromosomes, one chromosome can compensate for the other. Whereas people assigned male at birth have just one X chromosome, so they suffer debilitating symptoms as a result.²

Is there a cure for centronuclear myopathy?

There is currently no cure for centronuclear myopathy. The treatment for it is largely supportive therapy and includes physiotherapy, respiratory support, nutritional help in the form of a feeding tube, use of braces and splints, wheelchairs and other mobility aids to improve people’s quality of life. The people in the medical team will take you through all the ways you can support yourself, or if you’re a carer of the person with centronuclear myopathy, you may be given guides to read through, too.¹²

There are clinical trials for drugs that may potentially show promise of a cure; however, please note that there is a chance that you may not respond well or at all to the therapy given, or you might be allocated to the group that may not receive the treatment being offered. It is therefore important to apply whilst being informed. Places where you might find clinical trials are the National Organisation for Rare Diseases website or U.S government funded clinical trials in the United States for government funded clinical trials. Privately funded clinical trials can be found here, and any information regarding European clinical trials can be found here.

Summary

Centronuclear myopathy (CNM) is a rare, hereditary muscle disorder where cell nuclei are abnormally located in the centre of muscle fibres instead of the edges, leading to muscle weakness and other symptoms. It commonly appears from birth to adolescence but can also develop in adulthood. Diagnosis includes reviewing symptoms such as hypotonia (floppiness), delayed motor milestones, facial weakness, and breathing or swallowing difficulties. Further testing may involve muscle biopsy, MRI, EMG, and genetic testing.

There are three main types of CNM, each linked to different genetic mutations:

1. Myotubular Myopathy (X-linked recessive) – The most severe form, primarily affecting males. It can present before birth and is often fatal in infancy due to respiratory failure. Female carriers usually have no or mild symptoms
2. Autosomal Dominant CNM (e.g., DNM2 gene) – Often begins in adolescence or adulthood with symptoms like droopy eyelids (ptosis), eye muscle paralysis (ophthalmoplegia), and progressive limb weakness
3. Autosomal Recessive CNM (e.g., BIN1 gene) – Usually affects adolescents or young adults with similar but variable symptoms depending on the severity and muscle fibres involved

There is no cure, and treatment focuses on supportive care such as physiotherapy, respiratory aids, feeding support, and mobility devices. CNM is extremely rare, and due to limited genetic knowledge, up to 30% of cases may remain undiagnosed. Research and clinical trials are ongoing to find effective treatments.