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Disease Profile

Myhre syndrome

Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

<1 / 1 000 000

US Estimated

Europe Estimated

Age of onset






Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.


Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.


dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.


recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.


Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.


Not applicable


Other names (AKA)

Facial dysmorphism intellectual deficit short stature hearing loss; Laryngotracheal stenosis, arthropathy, prognathism, and short stature; LAPS syndrome;


Congenital and Genetic Diseases; Musculoskeletal Diseases; Nervous System Diseases


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]


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

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
80%-99% of people have these symptoms
Abnormality of the pubic bone
Abnormality of the pubic bones
Abnormality of the pubis

[ more ]

Abnormality of the ribs
Rib abnormalities
Short fingers or toes
Craniofacial hyperostosis
Excessive bone growth of the skull and face
Global developmental delay
Hearing impairment
Hearing defect

[ more ]

Hypoplasia of the maxilla
Decreased size of maxilla
Decreased size of upper jaw
Maxillary deficiency
Maxillary retrusion
Small maxilla
Small upper jaw
Small upper jaw bones
Upper jaw deficiency
Upper jaw retrusion

[ more ]

Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific

[ more ]

Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation

[ more ]

Joint stiffness
Stiff joints
Stiff joint

[ more ]

Large iliac wings
Mandibular prognathia
Prominent lower jaw
Prominent chin
Large lower jaw
Increased size of lower jaw
Increased projection of lower jaw
Big lower jaw

[ more ]

Midface retrusion
Decreased size of midface
Underdevelopment of midface
Midface deficiency

[ more ]

Narrow mouth
Small mouth
Flattened vertebrae
Severe short stature
Proportionate dwarfism
Short stature, severe

[ more ]

Short palm
Skeletal muscle hypertrophy
Increased skeletal muscle cells
Specific learning disability
Thin vermilion border
Decreased volume of lip
Thin lips

[ more ]

30%-79% of people have these symptoms
Abnormal cardiac septum morphology
Abnormality of epiphysis morphology
Abnormal shape of end part of bone
Abnormality of the metaphysis
Abnormality of the wide portion of a long bone
Narrow opening between the eyelids
Undescended testes
Undescended testis

[ more ]

EMG abnormality
High hypermetropia
Severe farsightedness
Severe long-sightedness

[ more ]

Drooping upper eyelid
Short palpebral fissure
Short opening between the eyelids
Thickened skin
Thick skin
5%-29% of people have these symptoms
Behavioral abnormality
Behavioral changes
Behavioral disorders
Behavioral disturbances
Behavioral problems
Behavioral/psychiatric abnormalities
Behavioural/Psychiatric abnormality
Psychiatric disorders
Psychiatric disturbances

[ more ]

Bifid uvula
Clouding of the lens of the eye
Cloudy lens

[ more ]

External genital hypoplasia
Underdevelopment of external reproductive organs
Femoral hernia
Gingival cleft
Decreased activity of gonads
Inguinal hernia
Abnormally small eyeball
Precocious puberty
Early onset of puberty
Early puberty

[ more ]

Respiratory failure
Submucous cleft hard palate
Unilateral cleft lip
One sided cleft upper lip
1%-4% of people have these symptoms
Atrial septal defect
An opening in the wall separating the top two chambers of the heart
Hole in heart wall separating two upper heart chambers

[ more ]

Birth length less than 3rd percentile
Broad ribs
Wide ribs
Cleft lip


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]


Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.


    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]


    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Social Networking Websites

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

        • Genetics Home Reference (GHR) contains information on Myhre syndrome. This website is maintained by the National Library of Medicine.
        • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

          In-Depth Information

          • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Myhre syndrome. Click on the link to view a sample search on this topic.


            1. Starr LJ, Lindor NM, and Lin AE. Myhre Syndrome. GeneReviews. April 13, 2017; https://www.ncbi.nlm.nih.gov/books/NBK425723/.
            2. Myhre Syndrome. National Organization for Rare Disorders (NORD). 2015; https://www.rarediseases.org/rare-disease-information/rare-diseases/byID/1075/viewAbstract.
            3. Myhre syndrome. Genetics Home Reference. January 2013; https://ghr.nlm.nih.gov/condition/myhre-syndrome.
            4. Lin AE, Michot C, Cormier-Daire V, et. al. Gain-of-function mutations in SMAD4 cause a distinctive repertoire of cardiovascular phenotypes in patients with Myhre syndrome. Am J Med Genet A. October, 2016; 170(10):2617-2631. https://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.37739/abstract.

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