Noonan syndrome is a genetic disorder that prevents normal development in various parts of the body. A child may be affected by Noonan syndrome in various ways: unusual facial characteristics, short stature, heart defects, other physical problems, and sometimes mental retardation.

Noonan syndrome is caused by a genetic mutation and is acquired when a child inherits a copy of an affected gene from a parent. It can also occur as a spontaneous mutation in a child, meaning there’s no family history involved.

It’s estimated that Noonan syndrome occurs in one of 1,000 to 2,500 births. The cause is a mutation in a particular gene. Currently, scientists know of four genes that can cause Noonan syndrome. The mutation can be inherited from a parent who carries the defective gene (autosomal dominant), or it can develop because of a new mutation in children who don’t have a genetic predisposition for the disease. Children who have one parent with Noonan syndrome have a 50 percent chance of developing the disorder.

The four known genes that may mutate and cause Noonan syndrome are:

  1. PTPN11 gene – About half the people with Noonan syndrome acquire the disorder because of a mutation of a gene called PTPN11.

  2. SOS1 gene – As many as 20 percent of people with Noonan syndrome have the condition because of a defect in this gene.

  3. RAF1 gene – This gene is responsible for up to 15 percent of all cases of Noonan syndrome.

  4. KRAS gene – About 5 to 10 percent of people acquire the disorder because of a mutation in the gene KRAS. People with this type of mutation may have a more severe form of Noonan syndrome.

Defects in these genes cause them to produce proteins that are continually active. Because these genes play a role in the formation of many tissues throughout the body, this constant activation of their proteins disrupts the normal process of cell growth and division.

In some people, none of these genes have a mutation, which may mean that some other, still undiscovered genes cause Noonan syndrome. In rare cases, people who have Noonan syndrome characteristics also have another condition called Neurofibromatosis 1. People with these two conditions have a mutation in the neurofibromin 1 gene, which produces a protein that helps keep cells from growing too fast or in an uncontrolled way.

There’s no specific treatment for Noonan syndrome. Management focuses on controlling the disease’s symptoms and complications individually.

Signs & Symptoms

Facial features

The way your child’s face appears is one of the key clinical features leading to a diagnosis of Noonan syndrome. These features change depending on the age of your child:

  • Early infancy – A baby less than 1 month old may have wide-set and down-slanting eyes, low-set ears, a deep groove and wide peaks in the upper lip, a short neck and a low hairline on the back of the head.

  • Infancy- An infant may have prominent eyes with a downward slant and thickened lids, and a depressed root of the nose with a wide base and bulbous tip.

  • Childhood – There is often a lack of facial expression.

  • Adolescence – An adolescent’s face is typically wide at the forehead tapering to a pointed chin, the facial features become sharper and the eyes are less prominent, and the neck lengthens to reveal skin webbing or prominent neck (trapezius) muscles.

  • Adulthood – When a child with Noonan syndrome reaches adulthood, the crease that runs from the edge of the nose to the corner of the mouth becomes prominent and the skin may be wrinkled and appear transparent.

Heart disease

More than half of people with Noonan syndrome have congenital heart disease, accounting for some of the key signs and symptoms. Pediatric cardiologists may be the first doctors to see children with Noonan syndrome. Some forms of congenital heart disease are more common when associated with this disorder:

  • Pulmonary valve stenosis – This is the most common heart problem seen with Noonan syndrome. Pulmonary valve stenosis is a narrowing of the pulmonary valve, the flap of tissue that separates the lower right chamber (ventricle) of your heart from the artery that supplies blood to the lungs (pulmonary artery). The defect may occur by itself, or there can be additional associated defects.

  • Hypertrophic cardiomyopathy – This is abnormal growth or thickening of the heart muscle that affects as many as 30 percent of people with Noonan syndrome.

  • Structural defects – People with Noonan syndrome often have structural defects of the heart. The defects involve a hole in the wall that separates the two lower chambers of the heart (ventricular septal defect), or a condition that causes a narrowing of the arteries that carry blood to the lungs for oxygen (pulmonary artery stenosis).

Certain drugs may be effective in addressing some kinds of heart problems. If there’s a problem with your heart’s valves, surgery may be necessary. Your dentist may recommend preventive use of antibiotics prior to dental cleaning or surgeries. Your doctor may also recommend that your heart function be evaluated periodically.

Growth issues

Your child’s birth weight will likely be normal, but some children have difficulty with feeding, which can cause poor weight gain until about 18 months. The growth spurt that’s usually seen during adolescence may be delayed in your child, but because this disease causes bone maturity to be delayed, your child has the potential to continue growing into his or her 20s. By adulthood, about one-third of people with Noonan syndrome have normal height, but short stature is more common.

Musculoskeletal issues

An unusually shaped chest often with a sunken sternum (pectus excavatum) or raised sternum (pectus carinatum) often occurs in those with Noonan syndrome. Wide-set nipples and a short neck, often with extra folds of skin (webbed neck), also are common. Low muscle tone also may be present.

Learning disabilities

Many children with Noonan syndrome get along without difficulty in school — significant mental retardation is uncommon. About one-third of those with Noonan syndrome may have mild mental retardation. Still, it’s not uncommon for people with Noonan syndrome to go on to college, and some have earned advanced degrees.

Eye problems

Nearly all people with Noonan syndrome have abnormalities of their eyes and eyelids. Differences in the shape and size of the eyes are hallmark features. Often the iris is pale blue or green. Problems with the eye muscles (strabismus, or crossed eyes), refractive problems — astigmatism, nearsightedness (myopia), hypermetropia, rapid movement of the eyeballs (nystagmus) and problems with the nerves of the eyes are common.

Bleeding

Most people with Noonan syndrome have a history of abnormal bruising or bleeding. Sometimes the bleeding problem isn’t discovered until a person has surgery and experiences excessive bleeding (hemorrhage).

Lymphatic problems

Noonan syndrome can cause problems with the lymphatic system, which drains excess fluid from the body and helps fight infection. These problems can show up before or after birth and can be focused in a particular area of the body or may be widespread. The most common problem is excess fluid (lymphedema) on the back of the hands or top of the feet.

Genital and kidney problems

Many people, especially males, with Noonan syndrome can have problems with the genitals and kidneys. Kidney problems are generally mild and occur in a fairly small number of people with the syndrome. Puberty may be delayed in both boys and girls, but most females usually develop normal fertility. In males, however, fertility may not develop normally — often because of undescended testicles, a condition that’s common in males with Noonan syndrome.

Skin problems

Various problems that affect the color and texture of the skin are common. There’s also a tendency to develop thick scars after surgery. People with Noonan syndrome often have curly, coarse hair, or sparse hair.

Many of the symptoms associated with Noonan syndrome are treated just as they would be for anyone else experiencing a health problem. Taken together though, the many problems this disorder can cause require coordinated management of various symptoms by your doctor and medical specialists who also may be part of your health care team.

Complications can arise that may require special attention, including:

  • Developmental issues – If your child is affected developmentally, he or she may have difficulty with organization and spatial sense. Sometimes the developmental challenges are severe enough to require a special plan of action to address your child’s learning and educational needs.

  • Bleeding and bruising – Noonan syndrome can cause excessive bleeding and bruising. This can create problems during surgery or dental work. If excess bleeding and bruising affect you, avoid aspirin or aspirin-containing products because aspirin can thin your blood. Children in general need to avoid aspirin because of its association with Reye’s syndrome.

  • Complications from lymphatic problems – Sometimes fluid can collect in the cavity around the heart and lungs, requiring a chest tube to drain. If the draining is prolonged or needs to be repeated, this can sometimes result in weight loss or infection, and this in turn can lead to additional complications.

  • Genital and urinary tract complications – Males may have a low sperm count and other fertility problems because of undescended testicles (cryptorchidism). Structural abnormalities in the kidneys may increase the rate of urinary tract infections.

Treatment of the symptoms and complications that occur with Noonan syndrome depends on their type and severity. Many of the health and physical issues associated with this disease are treated just the way they are in the general population.

Source: MayoClinic.com