Noonan Syndrome

What causes Noonan syndrome

Noonan syndrome is caused by changes (variants) in genes that control the RAS-MAPK pathway, a signaling system that regulates cell growth and division. Genes involved include:

• PTPN11 (about half of cases)
• SOS1, RAF1, RIT1, KRAS and several others

It is inherited in an autosomal dominant pattern: a parent with Noonan syndrome has a 1 in 2 chance of passing it to each child. Many cases arise new, with no family history. Mildly affected parents are sometimes diagnosed only after their child is.

Noonan syndrome belongs to a group called RASopathies, which also includes neurofibromatosis type 1, cardiofaciocutaneous syndrome and Costello syndrome.

Signs and features

Face

Features are often most noticeable in infancy and childhood and become subtler with age:

• wide-set, down-slanting eyes
• droopy eyelids (ptosis)
• low-set, backward-rotated ears with thick edges
• a deep groove between the nose and upper lip, with a high-peaked upper lip
• a broad forehead
• a short, broad or webbed neck with a low hairline

Growth

• normal birth length, then slower growth, so many children are shorter than peers
• delayed puberty
• feeding difficulties in infancy are common

Heart

Heart problems affect most people with Noonan syndrome:

• pulmonary valve stenosis: a narrowed valve between the heart and lungs, the most common
• hypertrophic cardiomyopathy: thickened heart muscle
• atrial septal defect and other structural defects
• abnormal ECG patterns

Other features

• chest shape differences: a sunken or protruding breastbone
• undescended testicles (cryptorchidism) in boys
• bleeding and bruising easily due to clotting factor or platelet problems
• lymphatic problems, such as swelling of the hands and feet or fluid around the lungs
• eye problems: strabismus, refractive errors
• hearing loss
• developmental delay, learning difficulties and speech problems in some, though many have normal intelligence
• skin and hair differences
• a slightly increased risk of certain childhood blood cancers, such as juvenile myelomonocytic leukemia

Diagnosis

• clinical evaluation of facial features, growth, heart and other findings
• genetic testing with a gene panel for RASopathies, which confirms the diagnosis in most cases
• heart evaluation with an echocardiogram and ECG
• blood clotting tests before surgery or dental work
• hearing, vision and developmental assessments
• prenatal clues: increased fluid behind the baby's neck on ultrasound, fluid buildup or heart defects can prompt testing during pregnancy

Noonan syndrome can resemble Turner syndrome, but it affects both sexes and has normal chromosomes.

Treatment and care

There is no cure. Care is tailored to each person's needs by a team that may include a pediatrician, cardiologist, geneticist, endocrinologist, hematologist and developmental specialists.

• heart: monitoring and, when needed, balloon valvuloplasty or surgery for pulmonary stenosis, and management of cardiomyopathy
• growth: growth hormone therapy is approved in the US for short stature in Noonan syndrome
• feeding: nutrition support, sometimes temporary tube feeding in infancy
• bleeding: checks before procedures, avoiding aspirin and NSAIDs where possible, and treatment plans for bleeding
• development: early intervention, speech and occupational therapy, and school support
• eyes and ears: glasses, patching or surgery for strabismus, hearing aids
• undescended testicles: surgery in early childhood
• genetic counseling for families

Outlook

Most people with Noonan syndrome live into adulthood and many have typical life expectancy, especially when heart problems are mild or treated. Severe hypertrophic cardiomyopathy in infancy carries more risk. Adults often have jobs and families, with ongoing heart monitoring.

Frequently asked questions

What are the features of Noonan syndrome?

Common features include wide-set, down-slanting eyes, droopy eyelids, low-set ears, a short or webbed neck, short stature, chest shape differences and heart defects, especially pulmonary valve stenosis. Features vary widely and may be subtle.

Is Noonan syndrome inherited?

It can be. It follows an autosomal dominant pattern, so an affected parent has a 50 percent chance of passing it to each child. Many cases, however, arise from a new genetic change with no family history.

What heart problems occur in Noonan syndrome?

Pulmonary valve stenosis is the most common, followed by hypertrophic cardiomyopathy (thickened heart muscle) and atrial septal defects. Regular heart checks with echocardiograms are part of lifelong care.

What is the life expectancy with Noonan syndrome?

Many people with Noonan syndrome have a normal or near-normal life expectancy. The main factor is the severity of heart disease, especially hypertrophic cardiomyopathy beginning in infancy. Regular monitoring and timely treatment improve outcomes.