Noonan Syndrome
Patient Information
Characteristics
Background and History
This disorder is named for Jacqueline Anne Noonan, an American pediatrician who described this disorder as a new syndrome in 1968. Some of the clinical features resemble those of a disorder in females caused by the loss of an X-chromosome (known as Turner syndrome) but Noonan syndrome in its several forms is caused by mutations in non-sex chromosomes. The number of chromosomes is normal.
Clinical Correlations
Noonan syndrome is a developmental disorder with widespread anomalies throughout the body. The face may have a triangular shape with downward-slanting eyelid openings, droopy eyelids (ptosis), wide spacing of the eyes, excessive skin folds in the upper eyelid, and posteriorly rotated ears. The neck is short and often webbed. Overall stature in 80% of individuals is also below normal. General development is mildly delayed and many patients have speech and language problems. Most have normal intelligence but some have a degree of intellectual disability. Males often are unable to reproduce as a result of undescended testes.
More than 90% of patients have eye anomalies or some kind of ocular disease, with crossing of the eyes, a lazy eye, cataracts, or corneal disease.
Genetics
Inheritance
Noonan syndrome inheritance usually follows an autosomal dominant pattern with direct vertical transmission of the syndrome. Fertility is often reduced, especially in males, but offspring of affected individuals have a 50% chance of passing the disease-causing mutation to their offspring. Mutations in at least 6 genes have been implicated. New mutations are common.
Pedigree
Autosomal dominant
Autosomal dominant disorders require only one mutation for the disease to be expressed. Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease. It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).
Autosomal dominant inheritance leads to a vertical pattern of transmission
Diagnosis and Prognosis
The diagnosis is usually made by a pediatrician but the wide variety of clinical features often requires the collaboration of other specialists. There is no treatment for the basic disorder but therapies are available for selective problems. Heart surgery may correct serious cardiac defects, special education may be helpful for those with cognitive difficulties, growth hormone has been tried for short stature, and bleeding problems may benefit from the use of special clotting factors.
Web Resources
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