Noonan syndrome - Causes of Noonan syndrome

Noonan syndrome is caused by a series of genetic mutations. A genetic mutation happens when there is an error in the copying process. This means some of the body’s processes will not work in the normal way.

Exactly how genetic mutations trigger the symptoms of Noonan syndrome is still unclear. However, it is thought they disrupt some of the proteins responsible for regulating cell growth and development. There is no evidence to support environmental factors as a cause, such as diet or radiation.

These mutations can be inherited (autosomal dominant inheritance) or happen entirely by chance (sporadic mutation).

There are at least eight genetic mutations linked to Noonan syndrome. The four most common are:

• the PTPN11 mutation - which accounts for around 50% of all cases
• the SOS1 gene mutation - which accounts for between 10-15% of cases
• the RAF1 gene mutation - which accounts for between 5-10% of cases 
• the KRAS gene mutation - which accounts for around 2% of cases

In an estimated 1 in 5 cases of Noonan syndrome no specific genetic mutation can be found.

Different mutations don't appear to cause different symptoms, with the following two exceptions:

• children with the PTPN11 gene tend to have pulmonary stenosis (a narrowed heart valve), a form of congenital heart disease
• children with the RAF1 gene tend to have cardiomyopathy (disease of the heart muscle)

Family history of Noonan syndrome

Around half of all people with Noonan syndrome have a known family history of the disorder. In these cases, one of the genes responsible for the condition is passed to them from one of their parents.

New gene mutations

In the other half of people with Noonan syndrome,  the disorder is caused by a new gene mutation.

In these cases, there is no family history of Noonan syndrome but a gene changes (mutates) spontaneously for the first time. The reason why this occurs is not yet fully understood.