National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Myhre syndrome


Other Names:
Facial dysmorphism - intellectual deficit - short stature - hearing loss; Laryngotracheal stenosis, arthropathy, prognathism, and short stature; LAPS syndrome; Facial dysmorphism - intellectual deficit - short stature - hearing loss; Laryngotracheal stenosis, arthropathy, prognathism, and short stature; LAPS syndrome; Growth mental deficiency syndrome of Myhre See More
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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
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

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.

Showing of 98 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormality of the pubic bone
Abnormality of the pubic bones
Abnormality of the pubis
[ more ] 		0003172
Abnormality of the ribs
Rib abnormalities
0000772
Brachydactyly
Short fingers or toes
0001156
Craniofacial hyperostosis
Excessive bone growth of the skull and face
0004493
Global developmental delay 0001263
Hearing impairment
Deafness
Hearing defect
[ more ] 		0000365
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 ] 		0000327
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation
[ more ] 		0001511
Joint stiffness
Stiff joint
Stiff joints
[ more ] 		0001387
Large iliac wings 0008818
Mandibular prognathia
Increased size of lower jaw
Increased projection of lower jaw
Big lower jaw
Prominent lower jaw
Prominent chin
Large lower jaw
[ more ] 		0000303
Midface retrusion
Decreased size of midface
Underdevelopment of midface
Midface deficiency
[ more ] 		0011800
Narrow mouth
Small mouth
0000160
Platyspondyly
Flattened vertebrae
0000926
Severe short stature
Dwarfism
Proportionate dwarfism
Short stature, severe
[ more ] 		0003510
Short palm 0004279
Skeletal muscle hypertrophy
Increased skeletal muscle cells
0003712
Specific learning disability 0001328
Thin vermilion border
Decreased volume of lip
Thin lips
[ more ] 		0000233
30%-79% of people have these symptoms
Abnormal cardiac septum morphology 0001671
Abnormality of epiphysis morphology
Abnormal shape of end part of bone
0005930
Abnormality of the metaphysis
Abnormality of the wide portion of a long bone
0000944
Blepharophimosis
Narrow opening between the eyelids
0000581
Cryptorchidism
Undescended testis
Undescended testes
[ more ] 		0000028
EMG abnormality 0003457
High hypermetropia
Severe farsightedness
Severe long-sightedness
[ more ] 		0008499
Hypertension 0000822
Ptosis
Drooping upper eyelid
0000508
Short palpebral fissure
Short opening between the eyelids
0012745
Thickened skin
Thick skin
0001072
5%-29% of people have these symptoms
Ataxia 0001251
Behavioral abnormality
Behavioral changes
Behavioral disorders
Behavioral disturbances
Behavioral problems
Behavioral/psychiatric abnormalities
Behavioural/Psychiatric abnormality
Psychiatric disorders
Psychiatric disturbances
[ more ] 		0000708
Bifid uvula 0000193
Cataract
Clouding of the lens of the eye
Cloudy lens
[ more ] 		0000518
Epispadias 0000039
External genital hypoplasia
Underdevelopment of external reproductive organs
0003241
Femoral hernia 0100541
Gingival cleft 0030690
Hypogonadism
Decreased activity of gonads
0000135
Hypospadias 0000047
Inguinal hernia 0000023
Microphthalmia
Abnormally small eyeball
0000568
Precocious puberty
Early onset of puberty
Early puberty
[ more ] 		0000826
Respiratory failure 0002878
Submucous cleft hard palate 0000176
Unilateral cleft lip
One sided cleft upper lip
0100333
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 ] 		0001631
Autism 0000717
Birth length less than 3rd percentile 0003561
Broad ribs
Wide ribs
0000885
Cleft lip 0410030
Cleft palate
Cleft roof of mouth
0000175
Hypoplastic iliac wing 0002866
Macrocephaly
Increased size of skull
Large head
Large head circumference
[ more ] 		0000256
Narrow palpebral fissure
Small opening between the eyelids
0045025
Obesity
Having too much body fat
0001513
Short philtrum 0000322
Small for gestational age
Birth weight less than 10th percentile
Low birth weight
[ more ] 		0001518
Stiff skin 0030053
Thickened calvaria
Increased thickness of skull cap
Thickened skull cap
[ more ] 		0002684
Thin upper lip vermilion
Thin upper lip
0000219
Ventricular septal defect
Hole in heart wall separating two lower heart chambers
0001629
Percent of people who have these symptoms is not available through HPO
2-3 toe syndactyly
Webbed 2nd and 3rd toes
0004691
Abnormality of the voice
Voice abnormality
0001608
Aortic valve stenosis
Narrowing of aortic valve
0001650
Autosomal dominant inheritance 0000006
Camptodactyly
Permanent flexion of the finger or toe
0012385
Clinodactyly
Permanent curving of the finger
0030084
Coarctation of aorta
Narrowing of aorta
Narrowing of the aorta
[ more ] 		0001680
Cone-shaped epiphysis
Cone-shaped end part of bone
0010579
Deeply set eye
Deep set eye
Deep-set eyes
Sunken eye
[ more ] 		0000490
Enlarged vertebral pedicles 0004621
Fine hair
Fine hair shaft
Fine hair texture
Thin hair shaft
Thin hair texture
[ more ] 		0002213
Generalized muscle hypertrophy
Generalized increase in muscle cell size
0003720
Hypermetropia
Farsightedness
Long-sightedness
[ more ] 		0000540
Hypertelorism
Wide-set eyes
Widely spaced eyes
[ more ] 		0000316
Laryngotracheal stenosis 0004894
Limitation of joint mobility
Decreased joint mobility
Decreased mobility of joints
Limited joint mobility
Limited joint motion
[ more ] 		0001376
Low-set ears
Low set ears
Lowset ears
[ more ] 		0000369
Malar flattening
Zygomatic flattening
0000272
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ] 		0000252
Microtia
Small ears
Underdeveloped ears
[ more ] 		0008551
Overlapping toe
Overlapping toes
Overriding toes
[ more ] 		0001845
Patent ductus arteriosus 0001643
Pericardial effusion
Fluid around heart
0001698
Prominent nasal bridge
Elevated nasal bridge
High nasal bridge
Prominent bridge of nose
Prominent nasal root
Protruding bridge of nose
Protruding nasal bridge
[ more ] 		0000426
Radial deviation of finger 0009466
Seizure 0001250
Short finger
Stubby finger
0009381
Short long bone
Long bone shortening
0003026
Short neck
Decreased length of neck
0000470
Short stature
Decreased body height
Small stature
[ more ] 		0004322
Short toe
Short toes
Stubby toes
[ more ] 		0001831
Sparse hair 0008070
Strabismus
Cross-eyed
Squint
Squint eyes
[ more ] 		0000486
Thick eyebrow
Bushy eyebrows
Dense eyebrow
Heavy eyebrows
Prominent eyebrows
Thick eyebrows
[ more ] 		0000574
Vertebral fusion
Spinal fusion
0002948
Showing of 98 |
Last updated: 7/1/2020
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
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

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]
Last updated: 5/10/2017

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

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

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.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • My 2 1/2 year old daughter has just been diagnosed with Mhyre syndrome. Could you provide me with information about this condition? Is there anything we should be aware of for later in life? See answer


  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; http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/1075/viewAbstract.
  3. Myhre syndrome. Genetics Home Reference. January 2013; http://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. http://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.37739/abstract.