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Hereditary myopathy with early respiratory failure
(often shortened to HMERF)
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Reviewed February 2012
What is HMERF?
Hereditary myopathy with early respiratory failure (HMERF) is an inherited muscle disease that predominantly affects muscles close to the center of the body (proximal muscles) and muscles that are needed for breathing.
The major signs and symptoms of HMERF usually appear in adulthood, on average around age 35. Among the earliest muscles affected in HMERF are the neck flexors, which are muscles at the front of the neck that help hold the head up. Other proximal muscles that become weak in people with HMERF include those of the hips, thighs, and upper arms. Some affected individuals have also reported weakness in muscles of the lower leg and foot called the dorsal foot extensors.
HMERF also causes severe weakness in muscles of the chest that are involved in breathing, particularly the diaphragm. This weakness leads to breathing problems and life-threatening respiratory failure.
How common is HMERF?
HMERF is a rare condition. It has been reported in several families of Swedish and French descent, and in at least one individual from Italy.
What genes are related to HMERF?
HMERF can be caused by a mutation in the TTN gene. This gene provides instructions for making a protein called titin. Titin plays an important role in muscles the body uses for movement (skeletal muscles) and in heart (cardiac) muscle.
Within muscle cells, titin is an essential component of structures called sarcomeres. Sarcomeres are the basic units of muscle contraction; they are made of proteins that generate the mechanical force needed for muscles to contract. Titin has several functions within sarcomeres. One of its most important jobs is to provide structure, flexibility, and stability to these cell structures. Titin also plays a role in chemical signaling and in assembling new sarcomeres.
The TTN gene mutation responsible for HMERF leads to the production of an altered version of the titin protein. Studies suggest that this change may disrupt titin's interactions with other proteins within sarcomeres and interfere with the protein's role in chemical signaling. Consequently, muscle fibers become damaged and weaken over time. It is unclear why these effects are usually limited to proximal muscles and muscles involved in breathing.
Some people with the characteristic features of HMERF do not have identified mutations in the TTN gene. In these cases, the genetic cause of the condition is unknown.
Read more about the TTN gene.
How do people inherit HMERF?
This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.
In most cases, an affected person has one parent with the condition.
Where can I find information about diagnosis or management of HMERF?
These resources address the diagnosis or management of HMERF and may include treatment providers.
General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.
To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.
Where can I find additional information about HMERF?
You may find the following resources about HMERF helpful. These materials are written for the general public.
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
What other names do people use for HMERF?
What if I still have specific questions about HMERF?
Where can I find general information about genetic conditions?
The Handbook provides basic information about genetics in clear language.
These links provide additional genetics resources that may be useful.
What glossary definitions help with understanding HMERF?
You may find definitions for these and many other terms in the Genetics Home Reference Glossary.
See also Understanding Medical Terminology.
References (5 links)
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.