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Genetics Home Reference: your guide to understanding genetic conditions     A service of the U.S. National Library of Medicine®

Myhre syndrome

Reviewed January 2013

What is Myhre syndrome?

Myhre syndrome is a condition with features affecting many systems and functions of the body.

People with Myhre syndrome usually have delayed development of language and motor skills such as crawling and walking. Most have intellectual disability that ranges from mild to moderate. Some have behavioral issues such as features of autism or related developmental disorders affecting communication and social interaction.

People with Myhre syndrome often have 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).

Growth is reduced in people with this disorder, beginning before birth and continuing through adolescence. Affected individuals have a low birth weight and are generally shorter than about 97 percent of their peers throughout life.

People with Myhre syndrome typically have stiffness of the skin and are usually described as having a muscular appearance. Skeletal abnormalities associated with this disorder include 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). Affected individuals often have joint problems (arthropathy), including stiffness and limited mobility.

Typical facial features in people with Myhre syndrome include 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). Some affected individuals also have an opening in the roof of the mouth (a cleft palate), a split in the lip (a cleft lip), or both.

Other features that occur in some people with this disorder include constriction of the throat (laryngotracheal stenosis), high blood pressure (hypertension), heart or eye abnormalities, and in males, undescended testes (cryptorchidism).

A disorder sometimes called laryngotracheal stenosis, arthropathy, prognathism, and short stature (LAPS) syndrome is now generally considered to be the same condition as Myhre syndrome because it has similar symptoms and the same genetic cause.

How common is Myhre syndrome?

Myhre syndrome is a rare disorder. Only about 30 cases have been documented in the medical literature. For reasons that are unknown, most affected individuals have been males.

What genes are related to Myhre syndrome?

Mutations in the SMAD4 gene cause Myhre syndrome. The SMAD4 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.

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.

Related Gene(s)

Changes in this gene are associated with Myhre syndrome.

  • SMAD4

How do people inherit Myhre syndrome?

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.

Where can I find information about diagnosis or management of Myhre syndrome?

These resources address the diagnosis or management of Myhre syndrome and may include treatment providers.

  • Centers for Disease Control and Prevention: Types of Hearing Loss (
  • Genetic Testing Registry: Myhre syndrome (
  • National Institute on Deafness and Other Communication Disorders: Communication Considerations for Parents of Deaf and Hard-of-Hearing Children (

You might also find information on the diagnosis or management of Myhre syndrome in Educational resources and Patient support.

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 Myhre syndrome?

You may find the following resources about Myhre syndrome 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 Myhre syndrome?

  • facial dysmorphism-intellectual deficit-short stature-hearing loss
  • LAPS syndrome
  • laryngotracheal stenosis, arthropathy, prognathism, and short stature

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines ( and How are genetic conditions and genes named? ( in the Handbook.

What if I still have specific questions about Myhre syndrome?

Ask the Genetic and Rare Diseases Information Center (

What glossary definitions help with understanding Myhre syndrome?

autism ; autosomal ; autosomal dominant ; brachydactyly ; cell ; cleft palate ; conductive hearing loss ; cryptorchidism ; deficiency ; disability ; gene ; growth factor ; hypertension ; hypoplasia ; inherited ; joint ; motor ; nucleus ; palate ; pelvis ; philtrum ; prognathism ; protein ; sensorineural ; short stature ; stature ; stenosis ; syndrome ; testes

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.


  • Burglen L, Héron D, Moerman A, Dieux-Coeslier A, Bourguignon JP, Bachy A, Carel JC, Cormier-Daire V, Manouvrier S, Verloes A. Myhre syndrome: new reports, review, and differential diagnosis. J Med Genet. 2003 Jul;40(7):546-51. Review. (
  • Caputo V, Cianetti L, Niceta M, Carta C, Ciolfi A, Bocchinfuso G, Carrani E, Dentici ML, Biamino E, Belligni E, Garavelli L, Boccone L, Melis D, Andria G, Gelb BD, Stella L, Silengo M, Dallapiccola B, Tartaglia M. A restricted spectrum of mutations in the SMAD4 tumor-suppressor gene underlies Myhre syndrome. Am J Hum Genet. 2012 Jan 13;90(1):161-9. doi: 10.1016/j.ajhg.2011.12.011. (
  • Le Goff C, Mahaut C, Abhyankar A, Le Goff W, Serre V, Afenjar A, Destrée A, di Rocco M, Héron D, Jacquemont S, Marlin S, Simon M, Tolmie J, Verloes A, Casanova JL, Munnich A, Cormier-Daire V. Mutations at a single codon in Mad homology 2 domain of SMAD4 cause Myhre syndrome. Nat Genet. 2011 Dec 11;44(1):85-8. doi: 10.1038/ng.1016. (
  • Lindor NM, Gunawardena SR, Thibodeau SN. Mutations of SMAD4 account for both LAPS and Myhre syndromes. Am J Med Genet A. 2012 Jun;158A(6):1520-1. doi: 10.1002/ajmg.a.35374. Epub 2012 May 14. (
  • Lindor NM. LAPS syndrome and Myhre syndrome: two disorders or one? Am J Med Genet A. 2009 Feb 15;149A(4):798-9. doi: 10.1002/ajmg.a.32719. (
  • McGowan R, Gulati R, McHenry P, Cooke A, Butler S, Keng WT, Murday V, Whiteford M, Dikkers FG, Sikkema-Raddatz B, van Essen T, Tolmie J. Clinical features and respiratory complications in Myhre syndrome. Eur J Med Genet. 2011 Nov-Dec;54(6):e553-9. doi: 10.1016/j.ejmg.2011.07.001. Epub 2011 Jul 21. (


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.

Reviewed: January 2013
Published: February 8, 2016