Ullrich congenital muscular dystrophy

The COL6A1, COL6A2, and COL6A3 genes give instructions on how to make a part of a protein called type VI collagen. Type VI collagen helps support muscle cell growth and stability. People who have mutations in the COL6A1, COL6A2, and COL6A3 genes do not make enough type VI collagen, and their bodies cannot make healthy muscle tissue. These spelling changes or differences with the COL6A1, COL6A2 or COL6A3 genes lead to a difference in the way that the type VI collagen is formed.

People with Ullrich congenital muscular dystrophy have a mutation in one of three possible genes. These genes are called COL6A1, COL6A2, and COL6A3. The COL6A1, COL6A2, and COL6A3 genes give instructions on how to make part of a protein called type VI collagen. Type VI collagen helps support muscle cell growth and stability.

People who have changes or mutations in the COL6A1, COL6A2, and COL6A3 genes do not make enough type VI collagen, and their bodies have trouble developing muscle.

We have two versions of each gene, one version from each parent. Ullrich congenital muscular dystrophy usually comes from having changes to both versions of one of these three genes. There is one report of Ullrich congenital muscular dystrophy occurring in a person who had a mutation in one version of two different genes (COL6A1 and COL6A2). There are also a few cases where people had Ullrich congenital muscular dystrophy when they had a mutation in just one version of one of the three genes. In those cases, the mutation was new in the person, and not inherited from a parent.

We cannot control what changes to our genes are made, and we cannot control which version of a gene a child inherits. There are no known environmental causes for Ullrich congenital muscular dystrophy. This means that having Ullrich congenital muscular dystrophy occurs by chance, not by action or inaction by any person.

If a child has Ullrich congenital muscular dystrophy, the child most likely has a medically significant change (mutation) or pathogenic variant on both versions of one of three genes known to cause Ullrich congenital muscular dystrophy. These three genes are: COL6A1, COL6A2, and COL6A3. A person has two versions of a gene because one version is inherited from each parent. This means that the parents of child with Ullrich congenital muscular dystrophy each most likely have one version of the gene with the pathogenic variant, and one version without. When a person has a mutation to one of the two versions of a gene and is healthy, the person is called a carrier.

Once an individual or child is identified to have Ullrich congenital muscular dystrophy, testing should start with the parents to see if they are carriers, or if the mutation is new in the child. If the parents are carriers, each one likely inherited the gene mutation from one of their parents. This means that their brothers and sisters could also be carriers. Testing is recommended for the aunts, uncles and siblings of an individual to see if they have the changed gene.

If an individual in the family is identified to be a carrier for Ullrich congenital muscular dystrophy they may have a risk or chance to have a child with Ullrich congenital muscular dystrophy. This risk or chance is dependent on if their partner also has a gene change in the same gene. When this happens and both individuals in a relationship are carriers, there is a 25% chance or 1 in 4 chance with each pregnancy to be affected by Ullrich congenital muscular dystrophy. Testing for family members of an individual with Ullrich congenital muscular dystrophy will identify them as a carrier or not. If they are identified to be a carrier, then their partner(s) can be tested to see if they are also a carrier.

Brothers and sisters of people who have Ullrich congenital muscular dystrophy have a 2/3 or 66% chance of being a carrier if they do not have the condition. Genetic testing to identify if siblings are carriers can be pursued when they are or reproductive age and are able to decide for themselves if they would like to know their carrier status for reproductive planning purposes.

Specialists that may be involved in the care of an individual with Ullrich congenital muscular dystrophy include:

The most common abbreviation for Ullrich Congenital Muscular Dystrophy is UCMD1.

People with Ullrich congenital muscular dystrophy have severe muscle weakness starting soon after birth. Most children with Ullrich congenital muscular dystrophy will learn to walk on their own. However, there are some people that never walk and others walk only with support. Those who can walk may lose the ability, usually in adolescence or by their teenage years. Individuals with Ullrich congenital muscular dystrophy develop stiffness and contractures in the muscles in their neck, hips, elbows, and knees. This can make it harder to move. Joints may be loose in the fingers, wrists, toes, ankles, and other areas. Some people need a machine to help them breathe. Additionally, scoliosis may develop and can be progressive requiring special surgical procedures to correct the severe curvature of the spine that can develop. Some people with Ullrich congenital muscular dystrophy have soft, velvety skin on the palms and soles. Some have abnormal wound healing.

The main symptoms of Ullrich congenital muscular dystrophy include muscle weakness that is present at birth or in early infancy that can progress. Muscle weakness is more prominent in the proximal muscles (the shoulders and hips) compared to the distal muscles (calves and forearms). Reflexes can be decreased or absent. Joints may be extra flexible in the hands, ankles, wrists and feet while joint contratures or stiffness can develop in the elbows, shoulders, knees and hips. The chest muscles may also be weak and there can be difficulties breathing as a result. Some individuals require a machine to assist with breathing, which may be used all the time or only at nights during sleep. Scoliosis (curvature of the spine) can develop and become progressive over time, requiring surgery. This can lead to additional concerns with breathing. Muscles can become atrophied (a term used to describe loss of muscle tissue) and individuals may appear slender. Some children are described as having failure to thrive, a term used to mean that they have difficulties gaining weight and growing compared to their same-aged peers.

No, Ullrich congenital muscular dystrophy is not screened for on the newborn bloodspot screening test. However, the signs or concerns of muscle weakness at birth or shortly after can indicate the need for a neurological assessment and may ultimately lead to the diagnosis.

You can find clinical trials through the Muscular dystrophy association or through clinicaltrials.gov

Through the Muscular Dystrophy Association, you can go to [link url="www.mda.org” target=”_blank”>www.mda.org. On their home page, click on "Hope Through Research" on the top. On the right side, click on "Clinical Studies and Trials." Then click on the "Congenital Muscular Dystrophy" link.

Through clinicaltrials.gov, go to https://clinicaltrials.gov/ct2/home and enter "Ullrich congenital muscular dystrophy" in the "Search for Studies" box.

There is no cure for Ullrich congenital muscular dystrophy. Treatment is based on the individual’s symptoms and features. People with Ullrich congenital muscular dystrophy may benefit from the following treatments:

About 0.13 per 1,000,000 people have Ullrich congenital muscular dystrophy.

Ullrich congenital muscular dystrophy is usually inherited in an autosomal recessive manner. There are three genes associated with Ullrich congenital muscular dystrophy. The COL6A1, COL6A2, and COL6A3 genes.

We have two copies of each of these genes- one version from each parent. Sometimes, a change occurs in a gene that causes it to not work correctly or as efficiently. This is known as a mutation or a pathogenic variant. Individuals that have an autosomal recessive condition have pathogenic variants in both copies of the same gene associated with Ullrich congenital muscular dystrophy. One non-working copy or gene change is inherited from the mother and one non-working copy or gene change is inherited from the father.

However, there is one report in the medical literature of an individual with Ullrich congenital muscular dystrophy that had a pathogenic variant identified in two different genes.

Individuals that have an autosomal recessive condition, have parents that are usually healthy and unaffected. This is because they have one working copy of the gene. They are called carriers. When a person has a child, one of the two copies of each gene is passed on during pregnancy. There is no way of controlling which version of a gene is passed on to a pregnancy. There is a 50% chance of passing the working copy of the gene, and a 50% chance of passing the non-working copy of a gene. If both people in a couple are carriers for the same genetic condition, they have a 25% chance of passing on both non-working versions of the gene with each pregnancy. A pregnancy that has inherited two non-working copies of either the COL6A1, COL6A2 or COL6A3 gene would have Ullrich congenital muscular dystrophy. The 25% risk or chance to have a child with Ullrich congenital muscular dystrophy is present with each pregnancy for a couple in which both the mother and the father are carriers.

There are three genes related to Ullrich congenital muscular dystrophy- COL6A1, COL6A2, and COL6A3. We have two copies of each gene- one version from each parent. Sometimes, a change to a gene makes it not work well or at all. If changing just one version of a gene causes health problems, then a condition is known as an autosomal dominant condition. Usually, Ullrich congenital muscular dystrophy comes from having a mutation in both copies of the same gene. However, there are reports of people with the condition having a mutation on just one copy of one of the three genes. In these cases, the mutation is usually a new change in the person with Ullrich congenital muscular dystrophy, and not inherited from either parent. There is a 50% chance for an individual to pass on their non-working copy of their gene that caused them to have Ullrich congenital muscular dystrophy if they have an autosomal dominant form of this condition.

There are multiple way to contribute to research for Ullrich Congenital Muscular Dystrophy.

You can support the Muscular Dystrophy Association by going to http://www.mda.org/ways-to-help. The page lists numerous ways to help. Links to make monetary donations are at the bottom of the page.

You support CureCMD by going to http://curecmd.org/studies/biobank and clicking on "Contribute" on the top. Scroll down and click on "Donate Now"

Testing for Ullrich congenital muscular dystrophy can be completed through a neurologist or geneticist. Testing may include genetic testing by bloodwork or a muscle biopsy. Genetic testing involves looking at the three different genes that can cause Ullrich congenital muscular dystrophy for disease-causing or significant changes in the spelling or instructions of the gene.

A muscle biopsy may be completed and can show or identify subtle or more significant changes in the muscle fibers. This can include a difference in the size of the muscle fibers, an increase in adipose (fatty) tissue within the muscle, increased number of internal nuclei (the command center of the muscle cell), and mild necrotic changes. Interstitial fibrosis within the muscle fibers may also be seen. Spaces may be seen between the muscle fibers and the connective tissue that is normally not present under an electron microscope.

To find a genetic professional near you who can discuss genetic testing, visit the following two sites: A listing of medical geneticists can be found at the American College of Medical Geneticists website ([link url="” target=”_blank”>www.acmg.net) and genetic counselors can be found on the National Society of Genetic Counselors website: [link url="” target=”_blank”>www.nsgc.org.

You can find clinical trials through the Muscular dystrophy association or through clinicaltrials.gov

Through the Muscular Dystrophy Association, you can go to [link url="www.mda.org” target=”_blank”>www.mda.org. On their home page, click on "Hope Through Research" on the top. One the right side, click on "Clinical Studies and Trials." Then click on the "Congenital Muscular Dystrophy" link.

Through clinicaltrials.gov, go to https://clinicaltrials.gov/ct2/home and enter "Ullrich Congenital Muscular Dystrophy" in the "Search for Studies" box.

The Muscular Dystrophy Association has over 200 treatment centers in the US and Puerto Rico. To find the nearest one to you, you can go to [link url="mda.org/locate” target=”_blank”>mda.org/locate, or call (800) 572-1717.

Genetic testing in family members of an individual diagnosed with Ullrich congenital muscular dystrophy is done by genetic testing in a blood or saliva sample. Testing can be completed once the specific genetic changes have been identified in the family member that has been diagnosed. Testing can be ordered by a geneticist, prenatal genetic counselor, maternal fetal medicine specialist or genetic counselor. It is helpful to share a copy of the test results for the family member that has been diagnosed with Ullrich congenital muscular dystrophy to ensure that the lab that is completing the testing is able to look for the specific changes seen in your family. This is known as single-site genetic testing.

You can locate a genetic counselor through [link url="www.nsgc.org” target=”_blank”>the National Society of Genetic Counselors who can assist you with locating a doctor or clinic for testing.

The Muscular Dystrophy Association is a support group for people affected by Ullrich congenital muscular dystrophy or that have a family member diagnosed with Ullrich congenital muscular dystrophy. At [link url="www.mda.org” target=”_blank”>www.mda.org you can find information about muscular dystrophy, equipment assistance, connection to summer camp, and help finding a local support group (http://www.mda.org/services/finding-support/support-groups).

On Facebook, you can become a member of the Muscular Dystrophy Association group (https://www.facebook.com/MDANational/). There is also a smaller group specific to Ullrich congenital muscular dystrophy called "Ullrich congenital muscular dystrophy Alex" at https://www.facebook.com/groups/785986071468207/.

Ullrich Congenital Muscular Dystrophy is also called:

Ullrich congenital muscular dystrophy is part of a group of disorders called collagen VI-related myopathy. Other conditions in this group are Bethlem myopathy, autosomal dominant limb-girdle muscular dystrophy, and autosomal recessive myosclerosis myopathy. Ullrich congenital muscular dystrophy is considered the most severe of the type VI-related myopathies.

Ullrich congenital muscular dystrophy may be suspected based on a muscle biopsy, however, additional genetic testing is necessary to confirm the diagnosis.

Genetic testing can be completed through a simple blood test ordered by a neurologist or geneticist. Genetic testing may look individually at each of the three genes that can cause Ullrich congenital muscular dystrophy or it can be completed as part of a "gene panel" in which all three genes are tested at the same time. Similarly, a doctor may choose to look at many different genes that can cause muscular dystrophies or muscle weakness, including a test known as whole exome sequencing or targeted exome sequencing.

Testing involves sequencing of each gene in which each letter or subunit within the gene is looked at to make sure there are not any medically significant changes in the gene. Testing can also include deletion/duplication studies, which are another type of genetic test in which each gene is looked at for small pieces that may be extra or missing within the gene. Sequencing and deletion/duplication studies are complimentary tests that both look at the genes responsible for Ullrich congenital muscular dystrophy but in slightly different ways.

Whole exome sequencing or targeted exome sequencing are also additional options for genetic testing. These tests look at the approximately 20,000 genes known to be associated with genetic conditions by sequencing or looking at each subunit within the gene. These changes are then compared through computer software that allows the lab to determine if a change is a significant change or not. Those changes that appear to possibly explain an individual’s medical concerns are then shared with your doctor for further interpretation and discussion.

To find a genetic professional near you who can discuss genetic testing, visit the following two sites: A listing of medical geneticists can be found at the American College of Medical Geneticists website ([link url="” target=”_blank”>www.acmg.net) and genetic counselors can be found on the National Society of Genetic Counselors website: [link url="” target=”_blank”>www.nsgc.org.