Noonan Syndrome


Medical Management Considerations


Resources for Families

Advisory Committee

Publication Information


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Description and Causes

Noonan syndrome (NS) is a multiple congenital anomaly syndrome inherited in an autosomal dominant pattern. Noonan syndrome is characterized by dysmorphic facies, short stature, ear abnormalities, cryptorchidism, ocular abnormalities, cardiovascular anomalies, cubitus valgus, webbed neck, and cutaneous and hair abnormalities.

Despite the presumed genetic link, the exact etiology is unknown; it has been hypothesized that NS patients have a genetic defect which alters prenatal development of the lymphatic vessels and disrupts tissue migration and organ placement during a critical period.   A candidate gene for this disorder has been mapped to 12q22-qter. Autosomal dominant inheritance with variable expression has been well documented, but many cases appear to be sporadic. Recent research suggests that parent-to-child transmission is more common than originally assumed.

Noonan syndrome is second only to Downs syndrome as one of the most common syndromes associated with congenital heart disease, accounting for 1.4% of children with cardiac defects and 17% of children undergoing surgery for pulmonary stenosis.

Growth retardation is a consistent feature of NS. Although children are not typically growth hormone deficient, a minority may have suboptimal growth hormone levels. The use of growth hormone therapy in NS is controversial and the subject of numerous current and previous research studies.

Developmental delay is frequent, and mild mental retardation, although relatively common (25%), is not constant. Children with NS have strengths in non-verbal reasoning, verbal comprehension, social judgment, and visual motor abilities. Specific weaknesses are found in spatial knowledge and planning abilities. Frequently, NS-affected individuals demonstrate problems with organization, memorization, and concentration. Studies show a wide range of IQ and a variable pattern of verbal-performance discrepancy.

The phenotype in Noonan syndrome changes consistently and predictably between infancy and adulthood. The differential diagnosis for patients with NS is extensive and includes XO/XX mosaicism, fetal hydantoin syndrome, fetal mysoline syndrome, Watson syndrome, cardiofaciocutaneous syndrome, Costello syndrome, and fetal alcohol syndrome have all been considered in patients with this phenotype.


Marked phenotoypic variability makes Noonan syndrome difficult to recognize in the newborn, and the changing phenotype with time often makes mild Noonan syndrome difficult to recognize in adults. Karyotype is normal; accurate prenatal diagnosis is not available, and no diagnostic tests exist. Diagnosis is purely clinical and subjective at present. In addition, maternal use of alcohol or other teratogens and identification of other chromosomal abnormalities must be considered to rule out competing diagnoses. Noonan syndrome should be suspected in infants who present with hypertrophic cardiomyopathy, (particularly if they also have valve dysplasia) and neonatal edema of the dorsum of hands and feet.

To help in making a diagnosis, Noonan (1994) indicates that the following features are typically present, though often difficult to discern in newborns: sloping forehead; thick ears which may be posteriorly positioned; hypertelorism with down-slanting of the palpebral fissures; deep-set groove of the upper lip; occasional retrognathia; marked edema of the neck, with excess skin on the back of the neck; relatively enlarged head from infancy through age 2; flat cheekbones with prominent, round eyes; depressed nasal bridge; stocky body, with chest deformities that become more prominent with age; and a short neck.


  • 1:1,000 to 1:2,500 live births (1:1,000 to 1:1,250 per Noonan)
  • Males and females are equally affected
  • If case is familial, a 50% chance exists of passing the gene to one or more offspring
  • Maternal transmission is three times greater than paternal transmission

Characteristic Features

  • Webbing of the neck
  • Pectus excavatum
  • Thick, low-set or abnormally-shaped ears
  • Sagging eyelids (ptosis)
  • Hypertelorism
  • Epicanthal folds
  • Micrognathia
  • Delayed puberty
  • Cryptorchidism
  • Short stature
  • Curly hair
  • Congenital heart disease, generally pulmonary stenosis (50%)
  • Feeding problems and failure to thrive in early infancy
  • Delayed cognitive and speech development
  • Learning difficulties
  • Peripheral hand and feet edema in neonatal period

Common Associations

  • Hypertonia
  • Coagulation abnormalities (estimated 20%)
  • Thrombocytonpenia and partial deficiency of factors XI:C, XII:C, or XIII:C
  • Learning problems
  • Hearing loss
  • Mild mental retardation
  • Behavior problems
  • Scoliosis (10 – 15%)
  • Atrial septal defect (10%)
  • Ventricular septal hypertrophy (10%)
  • Ventricular septal defects (5%)
  • Club foot (10 – 15%)
  • Seizures (2 – 12%)
  • Early feeding difficulties (poor feeding and symptoms of GI dysfunction with vomiting, constipation, abdominal pain and bloating)
  • Occasional malignant hyperthermia with anesthesia has been observed


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Note: These considerations are in addition to the normal medical care provided to an individual without Noonan syndrome. All recommendations can be addressed through clinical examination by the primary care provider, unless otherwise noted.


  • Conduct routine cardiology, hearing and eye evaluations
  • Monitor psycho-educational interventions and parental support

Infancy or Early Childhood (Birth to 5 years)

  • Perform complete cardiovascular evaluation
  • Perform vision testing
  • Refer to otolaryngologist as necessary
  • Encourage appropriate testing to identify individual’s relative strengths and weaknesses regarding intellectual functioning
  • Encourage parents to pursue genetic counseling given the wide variability in expression
  • Encourage parents to investigate special education services
  • Refer patient and parents for psychological support
  • Monitor dental care
  • During surgical procedures make medical team alert to increased tendency for bleeding and malignant hyperthermia with anesthesia

Late Childhood (5 to 13 years)

  • Consider growth hormone treatment, if growth hormone deficiency is proven, based upon specific risks and benefits for each individual. The use of growth hormone therapy in NS is controversial and the subject of numerous current and previous research studies.
  • Monitor dental care
  • Observe and support learning language, and behavioral problems, motor delay, clumsiness, and specific learning disability with visual-spatial relationships
  • Observe and support learning to cope with behaviors such as stubbornness, pervasive preoccupation with social interactions with peers

Adolescence and Adulthood (13 years and over)

  • Refer for vocational training and preparation as appropriate
  • Monitor for dental and behavioral needs
  • Fertility is normal for males and females


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Peer-reviewed Journal Articles/Academies 

Cianfarani, S. (1999). Growth Hormone Therapy in Noonan Syndrome. The Journal of Pediatrics, 134(3), 385-386.

Cotterill, A. M., McKenna, W. J., Brady, A. F., Sharland, M., Elsawi, M., et al. (1996). The Short-term Effects of Growth Hormone Therapy on Height Velocity and Cardiac Ventricular Wall \Thickness in Children with Noonan’s Syndrome. Journal of Clinical Endocrinology and Metabolism, 81(6), 2291-2297.

Daoud, M. S., Dahl, P. R., and Su, W. P. (1995). Noonan Syndrome. Seminars in Dermatology, 14 (2), 140-144.

Goldstein, S. and Reynolds, C. R. (1999). Handbook of Neurodevelopmental and Genetic Disorders in Children, New York: Guilford.

Kelnar, C. J. (2000). Growth Hormone Therapy in Noonan syndrome. Hormone Research, 53, 77-81.

Noonan, J. A. (1999). Noonan Syndrome Revisited. The Journal of Pediatrics, 135(6), 667-668.

Noonan, J. A. (1994). Noonan Syndrome: An Update and Review for the Primary Pediatrician. Clinical Pediatrics, 33(9), 548-555.

Qiu, W. W., Yin, S. S., & Stucker, F. J. (1998). Audiologic Manifestations of Noonan Syndrome. Archives of Otolaryngology—Head & Neck Surgery, 118, 319-323.

Sarimski, K. (2000). Developmental and Behavioural Phenotype in Noonan Syndrome. Journal of Genetic Counseling, 11(4), 383-390.

Shah, N., Rodriguez, M., Louis, D., Lindley, K., & Milla, P. J. (1999). Feeding Difficulties and Foregut Dysmotility in Noonan’s Syndrome. Archive of Disease in Children, 81(1), 28-31.

van der Burgt, I., Thoonen, G., Roosenboom, N., Assman-Huylsmans, et al. (1999). Patterns of Cognitive Functioning in School-aged Children with Noonan Syndrome Associated with Variability in Phenotypic Expression. The Journal of Pediatrics, 135(6), 707-713.

Wood, A., Massarano, A., Super, M., & Harrington, R. (1995). Behavioural Aspects and Psychiatric Findings in Noonan’s Syndrome. Archive of Disease in Children, 72(2), 153-155.

Special Interest Groups/Other Publications

Genetic Alliance

4301 Connecticut Avenue NW, #404

Washington, DC 20008-2304

(800) 336-GENE helpline

(202) 966-5557

(202) 966-8553 fax

e-mail: [email protected]

National Organization for Rare Disorders, Inc. (NORD)

PO Box 8923

New Fairfield, CT 06812-8923

(203) 746-6518

e-mail: [email protected]


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The Noonan Syndrome Support Group, Inc.

P.O. Box 145

Upperco, MD 21155

(888) 686-2224

(410) 374-5245

e-mail: [email protected]


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Theodore A. Kastner, M.D., M.S.

Richard J. Brouette, M.D.

Felice Weber Parisi, M.D. M.P.H

Terrance D. Wardinsky, M.D.


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Funded by a grant from the California Department of Developmental Services

For more information, contact:

Center for Health Improvement

1330 21st Street, Suite 100

Sacramento, CA 95814

(916) 901-9645

This document does not provide advice regarding medical diagnosis or treatment for any individual case, and any opinions or statements contained in this document are not intended to serve as a standard of medical care. Physicians are encouraged to view the considerations presented in this document in light of evolving scientific information. This document is not intended for use by the layperson. Reproduction of this document may be done with proper credit given to California Department of Developmental Services and the Center for Health Improvement.