Noonan syndrome

DEFINITION

Noonan syndrome is a genetic disorder that prevents normal development in various parts of the body. A person can be affected by Noonan syndrome in various ways. These include unusual facial characteristics, short stature, heart defects, other physical problems and possible developmental delays.

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

There’s no specific treatment for Noonan syndrome. Management focuses on controlling the disease’s symptoms and complications. Growth hormone may be used to treat short stature in some people with Noonan syndrome.

CAUSES

The cause of Noonan syndrome is a mutation in a particular gene. Currently, scientists know of eight 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.

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.

SYMPTOMS

Facial features

The way a person’s face looks is one of the key clinical features that leads to a diagnosis of Noonan syndrome. These features change with age:

• Early infancy. A baby younger 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 nose that’s depressed at the top, with a wide base and bulbous tip.
• Childhood. A child’s face may appear expressionless, and his or her facial features may appear coarse or elongated.
• 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 extra folds of skin (webbed neck) 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

About 80 percent 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 associated with this disorder include:

• Valve disorders. 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). It’s the most common heart problem seen with Noonan syndrome. The defect may occur by itself, or there can be additional associated defects.
• Thickening of the heart muscle (hypertrophic cardiomyopathy). This is abnormal growth or thickening of the heart muscle that affects more than 20 percent of people with Noonan syndrome.
• Other 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).

Growth issues

Your child’s birth weight will likely be normal, but some children with Noonan syndrome have difficulty with feeding. This 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 late teens.

By adulthood, about one-third of people with Noonan syndrome have normal height, but short stature remains 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.

Learning disabilities

Intelligence isn’t affected for most people with Noonan syndrome. However, there is an increased risk of learning disabilities.

Special education in school may be necessary for some people with Noonan syndrome. Still, it’s usual for people with Noonan syndrome to finish high school, go on to college and have careers.

Eye conditions

A common sign of Noonan syndrome is abnormalities of the 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), farsightedness (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 condition isn’t discovered until a person has surgery and experiences excessive bleeding (hemorrhage).

Lymphatic conditions

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 conditions

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 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 conditions

Various problems that affect the color and texture of the skin are common. People with Noonan syndrome often have curly, coarse hair or sparse hair.

When to see a doctor

The signs and symptoms of Noonan syndrome can be subtle. If you suspect you or your child may have the disorder, see your primary care doctor or your child’s pediatrician. You or your child may be referred to a geneticist or a cardiologist. Noonan syndrome can be detected with molecular genetic testing. If your unborn child is at risk because of a family history of Noonan syndrome, prenatal tests may be available.