Life with CNM/MTM

Joshua Frase Foundation - What is myotubular myopathy?

What is Myotubular Myopathy? 

To view the best illustration of muscle funtion that I've ever seen produced by Alan Beggs click here

What is Myotubular Myopathy? 

Centronuclear (CNM) and X-linked Myotubular Myopathies (XLMTM) are rare genetic disorders (also known as orphan diseases). These particular genetic disorders affect skeletal muscle tissue. The severity of the disease differs from case to case, ranging from slightly debilitating to fatal. Most often, CNM and MTM will be present at birth, however, symptoms can manifest at any stage in life. A child born with either of these conditions will most likely be “floppy”, or in scientific terms show signs of “hypotonia” – which just means “low muscle tone”. Most of the time, these babies will also struggle with the ability to suck, swallow, and breathe on their own. 

Centronuclear vs. Myotubular Myopathies

 

 

Centronuclear myopathy is the umbrella term, under which includes several forms of myopathy including: XLMTM, Autosomal Dominant CNM, Autosomal Recessive CNM, and Autosomal Dominant CNM.  Often times, children affected with CNM will not experience a change in muscle weakness over time. Or, if they do, the change occurs slowly due to many factors like growth, respiratory status and orthopedic (bone) complications like scoliosis.

In general, people affected with autosomal CNM have generalized weakness of their skeletal muscles.  How severe the weakness is varies from person to person.  Some people with CNM can walk short distances, using a wheelchair or power chair for longer distances.  They may have trouble doing stairs since that requires a lot of leg strength.  Some may breath fine during the daytime but need breathing support at night.  Some people with CNM may develop curvature of the spine.  As children get older and their bodies get larger, they may find that they have a harder time moving around over time.  Some people with DNM2 CNM may find that their weakness progresses slowly over many years.

Myotubular Myopathy is the largest diagnosis within this community. The symptoms of MTM tend to be more severe, and children born with it will often experience skeletal problems, gait problems, respiratory and feeding challenges, and fatigability along with poor muscle development.  All of these symptoms will range in severity from child to child, and each case presents its own special challenges. Statistically, 50% of these children do not live past their 2nd birthday, but we’ve seen children in our community beat these odds over and over – just like our son Joshua, who lived almost to his 16th birthday. Life for these children may not be easy, but the joy far outweighs the pain.

How does CNM run in families?

X-Linked MTM - Over view of genetics

XLMTM is X-linked. This means that males only have one copy of the MTM1 gene while females have two. Most (over 80%) women with a son with XLMTM are carriers, meaning that they have one normal copy and carry one copy with a change that causes the protein not to work properly. Carriers have a 50% (1 in 2) chance that each of their sons will have XLMTM and a 50% change that each of their daughters will be a carrier. Women with a son with XLMTM who are not carriers have a much lower change of having a second child with XLMTM. Males with XLMTM will not pass the condition to any sons, but all of their daughters will be carriers.  In very rare cases, girls or women who are carriers can have symptoms of the disease.  Affected females are known as affected carriers. 

Autosomal: Recessive and Dominant CNM

DNM2-associated CNM is autosomal dominant. People with this condition have one normal copy of the DNM2 gene and one copy with a change that causes the protein not to work properly. Thus, people with DNM2-associated CNM have a 50% chance of passing it down to each child.

BIN1-associated CNM is autosomal recessive. People with this condition have changes on both copies of their BIN1 gene, causing them not to produce a protein that works properly. Thus, parents of a child with BIN1-associated CNM each have a mutation in one copy of their BIN1 gene, and they have a 25% change of having another child with the same condition. 

RYR1 mutations can be either spontaneous or inherited.  Along with CNM, mutations in this gene can also cause malignant hyperthermia susceptibility (MHS). MHS is a life threatening reaction to certain drugs used for general anesthesia. Identifying this risk factor is one reason to get genetic testing when someone is diagnosed with CNM.

TTN (Titin)  -related health conditions. Changes in the Titin protein may cause muscle weakness as well as heart problems. You will need to discuss with your doctor if and how your Titin variant affects your health, including your heart. For more vital information, view here Titin myopathy. 

A common heart problem caused by variants in the Titin gene is known as dilated cardiomyopathy.  Sometimes other heart issues are also present in people with changes in their Titin gene.  It is a good idea to have a checkup from a heart doctor if you have even a single variant in the Titin gene. This may also apply to family members. To learn more about Titin related disorders and to connect with the Titin community, please click here. 

SEPG - This gene encodes a protein with similarity to members of the myosin light chain kinase family. This protein family is required for myocyte cytoskeletal development. Studies in mouse have determined that a lack of this protein affected myocardial development. Multiple alternatively spliced transcript variants have been reported for this gene, but the full-length nature of only two variants that encode different protein isoforms has been defined. [provided by RefSeq, Mar 2010] 

Dilated Cardiomyopathy - A Guide for Parents  

Cardiomyopathy Work Up by Dr. John Lyn Jefferie, MD and the Cardiomyopathy Foundation. 

For more information on genetic inheritance click here

For information on genetic testing click here

 The Journey to Clinical Trials - Part 1 with Alan Beggs, PhD - Feb 1st, 2014 

           "Weak bodies hold the mightiest of spirits."  -Staceyanne Fontana

Gene Therapy: Your Questions Answered

A special Thank you to NORD for this outstanding video addressing our questions, hopes and concerns on gene therapy for patients and caregivers.

 

X-Linked Myotubular Myopathy Informative Video

The American Society of Gene & Cell Therapy (ASGCT) has a new patient-centered portal that is designed to help educate and inform patients, families, and the general public on the status and promise of gene and cell therapies. Thank you ASGCT for sharing this informative video.

 

Gene Therapy Infograph from the American Society of Gene & Cell Therapy

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