Introduction

A brief overview of Nemaline Myopathy

Nemaline Myopathy is a rare type of inherited myopathy. The symptoms of Nemaline Myopathy can start showing at any point in your life, including at birth, childhood or even adulthood. The symptoms of nemaline myopathy can vary depending on the severity of the disease. There are many different types of Nemaline Myopathy such as amish nemaline myopathy, typical congenital nemaline myopathy, intermediate nemaline myopathy, adult onset myopathy and childhood onset nemaline myopathy.² There are also other types of myopathies, which we will explore in this article.

Knowing which myopathy you have can help your medical team to understand the course and prognosis of the disease, which would also give you the knowledge and know what to expect. The purpose of this article is to give patients, families and other readers of this article an understanding of myopathies and the difference between nemaline myopathy and other types of myopathies.

Overview of myopathies 

As explained earlier, the word myopathy is a greek word and it translates into muscle disease. In this section we will be dissecting and categorising a few of the different types of myopathies

Congenital myopathies 

Congenital myopathies is a type of myopathy that appears at birth, meaning that the myopathy is inherited from either one or both parents. This type of myopathy can cause a wide range of severe symptoms. This includes the expected general muscle weakness and reduced muscle tone, which means the baby may appear “floppier” than expected. More severe symptoms can include difficulties swallowing and/or breathing. This type of myopathy is usually non-progressive, meaning that as time goes on the myopathy doesn't get worse, however it may not improve over time either.³ 

Muscular dystrophies

Muscular dystrophies are genetic conditions which can be inherited; they cause the muscles condition to weaken overtime. You can begin to show symptoms of muscular dystrophy at any time, signs and symptoms often appearing at childhood, however symptoms may also begin to present during adulthood. There are many different types of muscular dystrophies. The symptoms you show will depend on the type of muscular dystrophy; its also a progressive conditions, meaning that it will get worse over time. The rate at which the disease progresses is also dependent on the type of muscular dystrophy.⁴

Inflammatory myopathies 

Inflammatory myopathies are a group of autoimmune conditions that causes long term muscle inflammation, muscle weakness and even muscle pain. This is a rare condition that can affect both adults and children. There are many different types of inflammatory conditions, here are the 4 main types:

• Polymyositis- skeletal muscle on both sides of the body are affected
• Dermatomyositis- this may cause progressive muscle loss
• Inclusion body myositis- which is a slow and progressive muscle loss
• Necrotising autoimmune myopathy - this causes muscle weakness in both the upper and lower body⁵

While these are all inflammatory myopathies, they differ in the way the disease attacks the body. This means that they also require different treatments and may present differently. 

Metabolic and mitochondrial myopathies 

Metabolic and mitochondrial myopathies affect how energy is produced in skeletal muscles. The most common symptom of this type of myopathy is weakness, however there’s a wide range of other symptoms which are inclusive of rhabdomyolysis, myalgia (muscle pain) and myoglobinuria.⁶ While all myopathies can share the main symptom being weakness, the disease can progress very differently.

What Is nemaline myopathy? 

Nemaline myopathy is a type of myopathy that are more commonly congenital and they are more common than the myopathies mentioned above. They are a group of myopathies that are characterized by nemaline shaped rods in the muscle fibers, the name nemaline myopathy comes from the greek word “nema” which translates to thread in reference to rods as in biopsies they looked like threads. Its similar to the myopathies mentioned above as it can vary in severity from mild to lethal, it can also begin in childhood or adulthood, unlike some of the conditions above it is non progressive or can be slow to progress.⁸ Nemaline myopathy is caused by a mutation which is a change in the genes. The change can occur in one of twelve specific genes which are responsible for the structure of skeletal muscles. The mutations most commonly happen in NEB, ACTA1 and least common in TPM2 and TPM3.⁷ Nemaline myopathy can be diagnosed by a neurologist through finding out the family history, as its a genetic condition as well as blood tests. But the main diagnosis is through a muscle biopsy where a small sample of muscle is taken and ran under a microscope, the muscle sample would show the rod like shapes in the muscle samples. Symptoms on nemaline myopathies include, breathing problems, cardiac issues, low muscle tone and even swallowing problems (choking and coughing), which in turn affects diet.⁹

Key differences between nemaline myopathy and other common myopathies 

Nemaline myopathy compared to muscular fystrophies (e.g., duchenne muscular dystrophy)

One type of muscular dystrophy is Duchenne muscular dystrophy, In this section of the article I will use this disease to compare the key differences between muscular dystrophies and nemaline myopathy.

DMD is caused by the lack of dystrophin protein. This protein is responsible for muscle strength and integrity, so the lack of this protein can cause muscles to damage easily and become fragile. Like other muscular dystrophies DMD is progressive and degenerative which means that the disease gets worse over time as does the condition of the muscle cells. In contrast nemaline myopathies are usually non progressive but may also be progressive or slow to progress, with some cases even showing improvement with physical therapy.⁴ The genetic causes of the diseases are also different DMD is typically referred to as an X linked condition meaning that the gene responsible for DMD is on the X chromosome. Females carry 2 X chromosomes while males have one X and one Y chromosome. So if a male inherits the X chromosome with the DMD gene they will have DMD while is a female needs to inherit 2 X chromosomes from their mother and father to show the gene, if they only inherit one they will be known as a carrier, meaning they can pass on the gene but dont show any symptoms.¹⁰

Nemaline myopathy is typically an autosomal recessive which means in both male and female counterparts they need 2 copies of the gene to express the condition.¹¹

Nemaline myopathy compared to other congenital myopathies (eg. central core disease and myotubular myopathy)

In this section of the article we will be comparing nemaline myopathy to other congenital myopathies, such as central core disease (CCD) and myotubular myopathy.

As central core disease is a congenital myopathy, it presents at birth or early in childhood. This is a condition that affects the muscles it causes muscle weakness in the muscles nearest to the centre of the body. Common muscles affected include the hips, upper legs, upper arms and shoulders. This condition would present as floppiness due to the lack of tone. The lack of tone in the hip muscles can lead to hip dislocations, people with this condition may also suffer with joint tightness known as contractures, especially in the knees and hips. Scoliosis is also a common symptom of this condition, it occurs when the spine curves as are foot deformities.¹²

Whilst Nemaline myopathy can also be congenital it has many differences when compared to CCD. Nemaline myopathy doesn't feature skeletal abnormalities such as hip dislocation and scoliosis. CCD is caused by a change in the RYR1 gene which when functioning normally this gene provides instructions for muscles to contract and relax. When RYR1 is faulty muscles dont contract and relax as they should causing muscles weakness and improper development. In contrast nemaline myopathy has 12 potential genes that can cause one of many types of nemaline myopathy.¹¹

Myotubular myopathy is another type of congenital myopathy. This condition is an X linked recessive condition meaning that the affected gene is on the X chromosome and therefore the condition is more common in males.

Click here to learn more about X linked conditions and other inheritance patterns.

Muscle weakness and low tone in muscles are some of the main symptoms in myotubular myopathy, these symptoms can vary from mild to extremely severe where the individual may have weakness in swallowing and breathing. With this condition there may be signs before birth such as reduced movement within the womb. Typically there is a protein called myotubular which is responsible for development and maintenance of muscle cells. In people with myotubular myopathies there is a change in the gene (MTM1) which instructs the protein causing there to be an insufficient amount of the protein which leads to myotubular myopathy. Myotubular myopathy, similar to nemaline myopathy, is diagnosed through a series of diagnosis methods including physical exams, family history taking (as this condition is genetic), genetic testing, muscle scans and muscle biopsies. In a muscle biopsy of someone with myotubular myopathy there are telltale signs that can help confirm the diagnosis, such as abnormal cell nuclei positioning in the muscle cells.¹³ In nemaline myopathy the same range of testing is used however when a muscle biopsy is performed the results differ as in NM the telltale sign is rod shaped fibers called nemaline bodies in the muscle biopsy.¹⁴

Summary 

Nemaline myopathy is a type of myopathy that is characterized by rod-shaped bodies in muscle fibers, which other myopathies don’t have. It is usually non-progressive or slowly progressive, whereas conditions like Duchenne muscular dystrophy are degenerative. Genetically, NM can involve more than one gene mutation and it follows an autosomal recessive inheritance pattern, unlike X-linked conditions like Duchenne or myotubular myopathy. Unlike central core disease, nemaline myopathy doesn't have skeletal abnormalities such as scoliosis or hip dislocations. Diagnosis of NM relies on muscle biopsy showing nemaline rods,this helps distinguish nemaline myopathy from other congenital, inflammatory, dystrophic, or metabolic myopathies.