Noonan syndrome

• Causes, incidence, and risk factors

  Defects in four genes (KRAS, PTPN11, RAF1, SOS1) can cause Noonan syndrome. About half of those affected by Noonan syndrome have a PTPN11 mutation. Persons with a defect in the KRAS gene have a more severe form of Noonan syndrome. Those with defects in the RAF1 gene tend to have a particular heart problem (hypertrophic cardiomyopathy). Problems with these genes cause certain proteins involved in growth and development to become overactive.

  Noonan syndrome is inherited, which means it is passed down through families. It is an autosomal dominant condition. This means that only one parent has to provide the faulty gene for the baby to have the syndrome. However, the fact that some children do not have a parent with Noonan syndrome likely means that some cases are not inherited.

• Symptoms
  • Delayed puberty
  • Down-slanting or wide-set eyes
  • Hearing loss (varies)
  • Low-set or abnormally shaped ears
  • Mild mental retardation (only in about 25% of cases)
  • Sagging eyelids (ptosis)
  • Short stature
  • Small penis
  • Undescended testicles
  • Unusual chest shape (usually a sunken chest called pectus excavatum)
  • Webbed and short-appearing neck
• Signs and tests

  Examination may show an extra fold of skin above the eyes near the nose (epicanthal folds) and arms that may be held at an unusual angle.

  There may be signs of congenital heart disease (especially pulmonary stenosis, occasionally ASD).

  Blood tests to look at platelet count and blood factors may reveal signs of a bleeding tendency.

  Specific tests depend on what the symptoms are. For example, if there are signs of heart disease, an EKG, chest x-ray, or echocardiogram may be recommended. Hearing tests are recommended for those who have signs of decreased hearing.

  Genetic testing can identify the mutations in the four genes which cause Noonan syndrome.

• Treatment

  There is no single treatment for Noonan syndrome. Treatment focuses on the individual symptoms. Growth hormone has been used successfully to treat short stature in some persons with Noonan syndrome.

• Support Groups

  The Noonan Syndrome Support Group, Inc. -- www.noonansyndrome.org

• Expectations (prognosis)

  The expected outcome depends on the extent and severity of symptoms. Patients can lead normal lives.

• Complications
  • Accumulation of fluid in tissues of body (lymphedema, cystic hygroma)
  • Failure to thrive in infants
  • Low self-esteem
  • Male infertility in those with both testes undescended
  • Problems with the structure of the heart
  • Short stature
  • Social difficulties related to physical problems
• Calling your health care provider

  This condition may be detected on early infant exams. Evaluation by an experienced geneticist is often needed to diagnose Noonan syndrome.

• Prevention

  Couples with a family history of Noonan syndrome may want to consider genetic counseling before having children.

• References

  Rapaport R. Hypofunction of the Ovaries. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, eds. Nelson Textbook of Pediatrics. 18th Ed. Philadelphia, Pa: Saunders Elsevier; 2007: chap 587.

Review Date: 8/26/2009

Reviewed By: Chad Haldeman-Englert, MD, Wake Forest University School of Medicine, Department of Pediatrics, Section on Medical Genetics, Winston-Salem, NC. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.