The following information may help to address your question:
What is Myhre syndrome?
Myhre syndrome is a rare,
connective tissue disorder that affects many parts of the body. Signs and symptoms include fibrosis (thickening and scarring of connective
tissue),
intellectual disability, distinctive facial features, skeletal abnormalities, and/or various
birth defects. The syndrome may affect the structure or function of the heart, the
respiratory system, the
gastrointestinal system, and the skin.
[1][2] Myhre syndrome is caused by a
mutation in the
SMAD4 gene. The mutation typically occurs for the first time in an affected person. To date, no reported cases have been
inherited from a parent. Inheritance is
autosomal dominant, but there are no reported cases of a person with Myhre syndrome having children. Treatment addresses each symptom present and may include limiting the risk of trauma to tissues, surgery for birth defects or complications, and routine management of learning delays or behavioral problems.
[1]
Last updated: 5/9/2017
What are the signs and symptoms of Myhre syndrome?
Myhre syndrome can affect many
organs and systems of the body. Signs and symptoms may include:
[1][3]
- Fibrosis (thickening and scarring of connective tissue) that occurs on its own or after trauma or surgery; may affect the heart, lungs, digestive system and skin
- Mild to moderate intellectual disability
- Delayed language and motor development
- Congenital heart defects or developing heart problems such as obstruction of arteries, pericardial effusion, constrictive pericarditis, cardiomyopathy, or hypertension
- Respiratory defects, obstructive airway disease, or restrictive pulmonary disease
- Gastrointestinal (digestive) abnormalities
- Thickening of the skin
- Autistic-like behaviors
- Hearing loss
- Skeletal abnormalities including short stature, limited range of joint motion, thickening of the skull bones, vertebral (spine) abnormalities, broad ribs, underdeveloped hip bones, and short fingers and toes (brachydactyly)
- Distinctive facial features including narrow openings of the eyelids, deep-set eyes, narrow mouth, thin upper lip, and protruding jaw
- Cleft lip and/or cleft palate
Last updated: 5/9/2017
What causes Myhre syndrome?
Myhre syndrome is caused by mutations in the
SMAD4 gene. This gene gives the body instructions for making a
protein involved in sending chemical signals from the surface of
cells to the
nucleus of cells. The nucleus contains most of the cell's
genetic material. This specific signaling pathway allows the environment outside the cell to affect how the cell makes other proteins. The SMAD4 protein interacts with other proteins to control the activity of other genes that influence development both before and after birth.
[3]
Mutations in the
SMAD4 gene that cause Myhre syndrome have been found to cause a "gain-of-function" of the SMAD4 protein, causing increased stability.
[4][1] This disrupts the signaling pathway, and ultimately the ability of signals to properly communicate how other genes should function. This results in abnormal development of the skeleton, cardiac muscle, and
central nervous system, causing the symptoms of Myhre syndrome.
[1]
Last updated: 5/10/2017
How is Myhre syndrome inherited?
Myhre syndrome is an autosomal dominant condition.
[1] This means that having a change (mutation) in only one copy of the responsible gene in each cell is enough to cause features of the condition. There is nothing that either parent can do, before or during a pregnancy, to cause a child to have this condition.
In all reported cases of Myhre syndrome to date, the mutation causing the condition has occurred for the first time in a person with no
family history of Myhre syndrome.
[1] This is called a
de novo mutation.
De novo mutations are not inherited from a parent, but occur randomly.
When a person with a mutation that causes an autosomal dominant condition has children, each child has a 50% (1 in 2) chance to inherit that mutation. However, it has been reported that no person with Myhre syndrome has had children, although fertility in people with Myhre syndrome has not been studied.
[1]
Last updated: 5/10/2017
Is there anything we should be aware of for later in life?
Growth problems, abnormally stiff joints, and hearing impairment may not become obvious until late infancy or early childhood (and may continue on through adolescence). Periodic hearing tests are recommended. Muscle enlargement (generalized muscular hypertrophy) may also become more evident during childhood.
[2]
Last updated: 3/17/2014
How might Myhre syndrome be treated?
Treatment of Myhre syndrome depends on each symptom present. Special attention should be paid to limiting trauma to tissues. Specialists that are involved in assessing or treating people with Myhre syndrome include
cardiologists,
orthopedists, respiratory specialists (lung doctors),
gastroenterologists, and other healthcare professionals.
[1][2] Some abnormalities or complications may require surgery. Long-term follow up and regular clinical checkups are needed to recognize the onset of certain symptoms or complications.
[2]
Early intervention is important to ensure that children with Myhre syndrome reach their potential. Special services that may be helpful for children may include special remedial education, special social support,
physical therapy, speech therapy, or other services.
[2]
Last updated: 5/10/2017
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GARD Information Specialist
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