An Overview of Noonan Syndrome

Noonan syndrome is a condition that produces a characteristic physical appearance as well as physiological changes that impact the body’s function in several ways. Designated as a rare disease, it is estimated that this condition affects approximately 1 out of 1000 to 2500 people. Noonan Syndrome is not associated with any particular geographic region or ethnic group. 

While Noonan syndrome is not life-threatening, if you have the condition you may experience associated illnesses, including heart disease, bleeding disorders, and some types of cancer at some point during your lifetime. These associated health problems are anticipated in association with Noonan syndrome Your outcome will be much better if you schedule medical visits to monitor your health and obtain timely treatment for any medical issues that arise before they advance to cause serious consequences.

Identification

Identifying Noonan syndrome is based on the recognition of several associated manifestations. There can be a range in the severity of the illness, and some people may have more obvious physical features or a more substantial health impact than others.

If you already know that you have family members who have been diagnosed with Noonan syndrome, this may have prompted you to notice signs indicating that you or your child could be affected. Your healthcare provider may have recognized the combination of physical features, symptoms, and health aspects of the illness. The next step after identifying signs of the condition is to proceed with further investigation into whether you or your child has Noonan syndrome.

Characteristics

Noonan syndrome manifests both inside and outside the body, resulting in a characteristic appearance marked by physical traits of the condition, as well as medical problems caused by the condition.

• Physical appearance: The facial and bodily features of someone who has Noonan syndrome may appear to be quite unusual, or may appear to be fairly normal physical attributes. The most obvious physical descriptions associated with this condition are a larger than usual head size, eyes that are wide apart, and a somewhat shorter than average height.
• Head: The face and head of a person living with Noonan syndrome are often described as triangular shaped because the forehead is proportionately larger than the small jaw and chin.
• Eyes: The eyes are noted to be slanted downward, sometimes with an appearance that seems to wrap around the side of the face. The eyelids may be thick, creating deep skin folds.
• Neck: Noonan syndrome is also associated with a webbed neck, which means that people affected by this condition may have a thicker than usual neck with skin creases that appear to form a “web” between the upper chest and jaw.
• Swelling: Some people who have Noonan syndrome may experience swelling of the body, arms, legs or fingers. This has been described in babies as well as adults who have Noonan Syndrome and it is caused by edema, which is a build-up of fluid.
• Short height and fingers: Across cultures, people who have Noonan syndrome are found to be shorter than average, and may also have short fingers. Children with this condition are generally not smaller than average at birth, but grow slowly during infancy, and therefore the short height is something that begins to become noticeable during infancy or early childhood.

While Noonan syndrome is usually associated with certain facial features and body type, but there can be a wide range of how these features appear. Therefore facial and body appearance cannot reliably determine whether someone definitely has Noonan syndrome or not.

Symptoms

There are several symptoms of this condition, and they may or may not affect everyone who has Noonan Syndrome.

• Trouble eating: Some babies who have Noonan syndrome might not eat as well as normal babies of the same age, and this may cause trouble gaining weight and delayed growth.
• Heart problems: The most common health concern associated with Noonan syndrome is a heart problem called pulmonary valve stenosis. This problem interferes with blood flow from the heart to the lungs, resulting in symptoms such as fatigue, shortness of breath, or blue appearance of the lips or fingers. After a while, people with untreated pulmonary valve stenosis may develop an enlarged heart, which also causes fatigue and may result in serious heart problems, such as heart failure, as time goes on. There are other heart defects associated with Noonan syndrome as well, including hypertrophic obstructive cardiomyopathy, atrial septal defect, and ventricular septal defect.
• Bruising or Bleeding: Noonan syndrome may cause blood-clotting problems, which results in excessive bruising as well as bleeding for a longer than usual period of time after injury. 
• Vision changes: At least half of children who have Noonan syndrome have problems with vision and eye movement, such as a lazy eye or a deviated eye.
• Weak bones: Children and adults who have Noonan syndrome may have problems with bone formation and bone strength, resulting in fragile bones that can break more easily than usual or that may result in an unusual body structure, particularly of the chest. An example of the unusual bone structure that may occur with Noonan syndrome is a deep “pit” in the upper chest. It is not clear why this occurs, and it does not affect everyone who has Noonan syndrome.
• Sexual maturation: Boys and girls who have Noonan syndrome may experience delayed puberty. Some boys have undescended testicles and may experience decreased fertility later in life.
• Learning delay: There is an association between learning disorders and Noonan syndrome, although the link is not strong. In general, the current information about cognitive development of individuals with Noonan syndrome suggests that children who have the condition have a higher than average chance of having a learning disability, although it is more common for children and adults who have Noonan syndrome to have average intellectual ability—and above average intellectual ability has been seen as well.

Diagnosis

The most definitive evidence of Noonan syndrome is a genetic test. However, it is estimated that between 20 to 40 percent of people who are diagnosed with Noonan syndrome do not have a family history of the condition or do not have the characteristic abnormalities detected by genetic testing. Sometimes, other tests and observations can support the diagnosis.

• Laboratory tests: Blood tests to assess blood-clotting function may be normal or abnormal in people who have Noonan syndrome. There is not a strong correlation between the blood tests that assess blood clotting and the symptoms of bruising or bleeding.
• Heart function tests: The diagnosis of pulmonary hypertension as well as the other heart defects that are associated with Noonan syndrome can support the diagnosis of this condition. However, all of the heart conditions that are associated with this syndrome can occur in other circumstances as well; the identification of one of the heart conditions does not confirm Noonan syndrome, and the absence of a heart problem does not mean that a person doesn’t have Noonan syndrome.
• Genetic testing: There are several genes that have been associated with Noonan syndrome, and if these genes are identified, especially among family members, this can be a diagnostic confirmation of the syndrome.

What to Expect

Life expectancy with Noonan syndrome is generally normal, but there may be health problems that need to be addressed with medical or surgical attention.

• Bleeding can result in blood loss, which can cause symptoms of fatigue. Less commonly, excessive bleeding can cause loss of consciousness or emergency need for blood transfusions.   
• Heart disease is the most common health effect of Noonan syndrome. The heart disease can result in heart failure, and therefore it is important to maintain routine follow up with a cardiologist if you or your child has Noonan syndrome. 
• If you have Noonan syndrome, there is an increased chance of certain types of cancer, particularly blood cancers, such as juvenile myelomonocytic leukemia and neuroblastoma.

Treatment

The treatment of Noonan syndrome is focused on several aspects of the disease.

• Preventing serious heart problems: Early diagnosis and management of heart problems can prevent long-term health consequences. Depending on the severity and type of heart condition, medication, surgery or close observation may be the best option for you.
• Identifying and treating medical complications: Noonan syndrome is associated with varied health complications ranging from bleeding to infertility to cancer. So far, there is no test that can predict whether you will develop one of more of these problems before they begin to affect the body. Close medical care includes regularly scheduled medical visits so that your healthcare provider can identify emerging problems through your medical history and physical examinations while they are still treatable. 
• Promoting normal growth: Growth hormone has been used in some children who have Noonan Syndrome as a way to stimulate growth, which helps in attaining optimal height and bone shape and structure. While growth hormone has been used as a successful strategy for children with Noonan syndrome, levels of growth hormone as well as other hormones are not abnormal for people who have this condition.
• Genetic counseling: This condition is usually hereditary and some parents may want to have as much information as possible about the risk of certain diseases such as Noonan syndrome when planning a family.

Causes

Noonan syndrome is a combination of physical characteristics and health problems that are rooted in a protein defect that is often caused by a genetic abnormality.

The genetic abnormality alters a protein that is involved in modifying the rate at which the body grows.

This protein specifically functions in the RAS-MAPK (mitogen-activated protein kinase) signal transduction pathway, which is a key part of cell division. This is significant because the human body grows through the process of cell division, which is the production of new human cells from already existing cells. Cell division essentially results in two cells instead of one, which produces growing body parts. This is especially important during infancy and childhood when a person is growing in size. But cell division continues throughout life as the body repairs, regenerates, and renews. This means that problems with cell division can affect many organs throughout the body. This is why Noonan syndrome has so many associated physical and cosmetic manifestations.   

Because Noonan syndrome is caused by alterations in the RAS-MAPK, it is specifically called a RASopathy. There are several RASopathies, and they are all relatively uncommon disorders.

Genes and Heredity

The protein malfunction of Noonan syndrome is caused by a genetic defect. This means that the genes in the body that code for the protein responsible for Noonan syndrome have a faulty code, normally referred to as a mutation. The mutation is usually hereditary, but it may be spontaneous, meaning that it occurred without being inherited from a parent. 

It turns out that there are four different gene abnormalities that can cause Noonan syndrome. These genes are the PTPN11 gene, the SOS1 gene, the RAF1 gene, and the RIT1 gene, with defects of the PTPN11 gene comprising about 50% of instances of Noonan Syndrome. If a person inherits or develops any of these 4 gene abnormalities, Noonan Syndrome is expected to occur.

The condition is inherited as an autosomal dominant disease, which means that if one parent has the disease, then the child will also have the disease. This is because inheritance of this particular genetic abnormality from one parent causes a defect in the RAS-MAPK protein production that cannot be compensated for even if an individual also inherits a gene for normal production of the protein.

There are instances of sporadic Noonan Syndrome, which means that the genetic abnormality can arise in a child who did not inherit the condition from parents. A person who has sporadic Noonan syndrome may have a child with the condition because an affected person’s children can inherit the new genetic abnormality.

A Word From Verywell

If you or your child has Noonan syndrome, it is important to maintain regular visits with your healthcare provider and to learn how to recognize the associated symptoms. Some individuals and families who have rare diseases such as Noonan syndrome find it helpful to connect with advocacy groups and support groups, who can provide updated information and hard to find resources about the condition. Additionally, you might want to ask your healthcare provider about the latest experimental trials so that you can keep up to date on new treatments and possibly participate in a research trial yourself.