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Genetic and Rare Diseases Information Center (GARD)

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Myhre syndrome


Other Names for this Disease

  • Facial dysmorphism - intellectual deficit - short stature - hearing loss
  • Growth mental deficiency syndrome of Myhre
  • LAPS syndrome
  • Laryngotracheal stenosis, arthropathy, prognathism, and short stature
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.

Your 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?

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

What is Myhre syndrome?

Myhre syndrome is a rare inherited disorder characterized by intellectual disability, short stature, unusual facial features, and various bone (skeletal) abnormalities. Other findings may include hearing impairment, abnormal enlargement of the muscles (muscle hypertrophy), and/or joint stiffness.[1] Myhre syndrome is caused by mutations in the SMAD4 gene. This condition is inherited in an autosomal dominant pattern. Most cases are due to a new mutation.[2]
Last updated: 3/17/2014

What are the symptoms of Myhre syndrome?

Myhre syndrome is a condition with features affecting many systems and functions of the body. Associated findings might include:[2]
  • Delayed development of language and motor skills such as crawling and walking
  • Intellectual disability that ranges from mild to moderate
  • Behavioral issues such as features of autism or related developmental disorders affecting communication and social interaction
  • Hearing loss, which can be caused by changes in the inner ear (sensorineural deafness), changes in the middle ear (conductive hearing loss), or both (mixed hearing loss)
  • Reduced growth, beginning before birth and continuing through adolescence and affecting weight and height (many are shorter than about 97 percent of their peers)
  • Stiffness of the skin resulting in a muscular appearance
  • Skeletal abnormalities including thickening of the skull bones, flattened bones of the spine (platyspondyly), broad ribs, underdevelopment of the winglike structures of the pelvis (hypoplastic iliac wings), and unusually short fingers and toes (brachydactyly)
  • Joint problems (arthropathy), including stiffness and limited mobility
  • Typical facial features including narrow openings of the eyelids (short palpebral fissures), a shortened distance between the nose and upper lip (a short philtrum), a sunken appearance of the middle of the face (midface hypoplasia), a small mouth with a thin upper lip, and a protruding jaw (prognathism)
  • An opening in the roof of the mouth (a cleft palate), a split in the lip (a cleft lip), or both
  • Constriction of the throat (laryngotracheal stenosis)
  • High blood pressure (hypertension)
  • Heart or eye abnormalities
  • In males, undescended testes (cryptorchidism)
Last updated: 3/17/2014

What causes Myhre syndrome?

Myhre syndrome is caused by mutations in the SMAD4 gene. This gene provides instructions for making a protein involved in transmitting chemical signals from the cell surface to the nucleus. This signaling pathway, called the transforming growth factor beta (TGF-β) pathway, allows the environment outside the cell to affect how the cell produces other proteins. As part of this pathway, the SMAD4 protein interacts with other proteins to control the activity of particular genes. These genes influence many areas of development.[2]

Some researchers believe that the SMAD4 gene mutations that cause Myhre syndrome impair the ability of the SMAD4 protein to attach (bind) properly with the other proteins involved in the signaling pathway. Other studies have suggested that these mutations result in an abnormally stable SMAD4 protein that remains active in the cell longer. Changes in SMAD4 binding or availability may result in abnormal signaling in many cell types, which affects development of several body systems and leads to the signs and symptoms of Myhre syndrome.[2]

Last updated: 3/17/2014

How is Myhre syndrome inherited?

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. Most cases result from new (de novo) mutations in the gene that occur during the formation of reproductive cells (eggs or sperm) or in early embryonic development. These cases occur in people with no history of the disorder in their family.[2]
Last updated: 3/17/2014

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.[1]
Last updated: 3/17/2014

How might Myhre syndrome be treated?

Treatment of this condition is symptomatic and supportive. Children with Myhre syndrome may require management by a team of specialists, including pediatricians, speech pathologists, orthopedists (bone specialists), cardiologists (heart specialists), audiologists (hearing specialists), and physical therapists. Early intervention is important to help ensure that children with Myhre syndrome reach their full potential.[1]
Last updated: 3/17/2014

References
Other Names for this Disease
  • Facial dysmorphism - intellectual deficit - short stature - hearing loss
  • Growth mental deficiency syndrome of Myhre
  • LAPS syndrome
  • Laryngotracheal stenosis, arthropathy, prognathism, and short stature
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.