Noonan syndrome
Introduction
Noonan syndrome is named after an American paediatric cardiologist (children’s heart specialist) called Jacqueline Noonan.
During the 1960s, she noticed that many children attending her clinic with narrowing of the pulmonary valves were also short and had similar facial features.
Noonan syndrome is a genetic disorder that can cause a wide range of potential symptoms which can vary from person to person. The three most common symptoms are:
- short stature
- distinctive and unusual physical features, such as a wider than usual distance between the eyes and a triangular-shaped face
- congenital heart disease, which is where a baby is born with one or more defects that affect the normal function of their heart
The severity of the symptoms of Noonan syndrome can range from mild to life-threatening.
The condition is usually diagnosed at birth, although milder cases may go undiagnosed until a child gets older.
Noonan syndrome is relatively uncommon. It is estimated that 1 in 1,000 to 2,500 children are born with it. It affects both sexes and all ethnic groups equally.
What causes Noonan syndrome?
Researchers have identified four specific genetic mutations that cause Noonan syndrome. A genetic mutation happens when the normal instructions that are carried in certain genes become scrambled. This means that some of the body’s processes don't work in the normal way.
However, it is unclear exactly how these mutations cause all the symptoms associated with Noonan syndrome.
Read more about causes of Noonan syndrome.
There is currently no cure for Noonan syndrome, so treatment involves trying to manage the various symptoms and complications that can arise from the condition.
Read more about treatment for Noonan syndrome.
Outlook
The outlook for children with Noonan syndrome depends on how serious their congenital heart disease is (although only 80% of children with Noonan syndrome will have congenital heart disease). Some types of congenital heart disease are mild and only require careful monitoring. Other types are life-threatening and require immediate emergency surgery.
However, due to advancements in heart surgery, almost all children with congenital heart disease will survive into adulthood. Most adults with Noonan syndrome do not require specialist medical care but may benefit from occasional cardiac follow-up. They are usually able to lead full and independent lives.
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Symptoms
There are many different symptoms associated with Noonan syndrome and not everyone with the disorder will have all of them. The symptoms also vary in severity.
The three most common symptoms of Noonan syndrome are:
- unusual physical features
- short stature
- congenital heart disease (heart defects that are present at birth)
Each symptom is discussed in more detail below.
Unusual features
Unless your child’s symptoms are very mild, unusual facial features usually become apparent following birth and include:
- a broad forehead
- a wider than usual distance between the eyes
- drooping eyelids
- low-set ears that are rotated towards the back of the head
- a small jaw
- a short neck with excess skin folds
- a lower than usual hairline at the back of the head and neck
As your child gets older, it is likely that their face will become more triangular and their eyelids will begin to droop. Their lips may also thicken and the folds of skin that run from each side of the nose to the corners of the mouth (the nasolabial folds) may become more noticeable.
As your child reaches their teenage years, their eyes will become less prominent and their neck should become longer. However, the lengthening of the neck can reveal extensive folds of skin (skin webbing).
As your child reaches adulthood, it is likely that their nasolabial folds will become even more prominent and their eyelids will take on a thick, hooded appearance.
Children with Noonan syndrome will have abnormalities that affect the bones of the chest such as:
- a chest that sticks out or sinks in
- an usually wide chest with a large distance between the nipples
Short stature
Children born with Noonan syndrome will usually be a normal length at birth, and their short stature will not usually become apparent until they are around two years old.
After that time, they won't grow as quickly as children of the same age. Puberty (when a child begins to mature sexually and physically) will typically be delayed for up to two years. The expected growth spurt that should happen during puberty is either reduced or doesn’t happen at all.
This is sometime treated with a type of medication, known as human growth hormone.
If left untreated, the average adult height for men with Noonan syndrome is 162.5cm (5ft 3in) and for women is 153cm (5ft).
Congenital heart disease
An estimated 90% of children with Noonan syndrome will have some form of congenital heart disease. This may be one of the following:
Pulmonary stenosis
Pulmonary stenosis is the most common type of congenital heart disease, affecting around half of all children with Noonan syndrome. It occurs when the pulmonary valve (the valve that helps control the flow of blood away from the heart and into the lungs) is unusually narrow. This means that the heart has to work much harder to pump blood into the lungs. In many cases there will be no symptoms and no treatment is required, but if the obstruction is severe it can be corrected by surgery (see below).
Hypertrophic cardiomyopathy (HCM)
Hypertrophic cardiomyopathy (HCM) is the second most common type of congenital heart disease in children with Noonan syndrome, affecting an estimated 10-20% of children.
In cases of HCM, the muscles of the heart are much larger than they should be. This can place strain on the heart and cause symptoms such as breathlessness.
HCM in Noonan syndrome can cause heart failure in infancy. However, the HCM in Noonan syndrome improves with age.
Septal defects
A septal defect is a hole between two of the chambers of the heart, often referred to as having a ‘hole in the heart’. The hole can be between the upper chambers (atrial septal defects) or the lower chambers (ventricular septal defects).
Read more about congenital heart disease.
Other symptoms
Other, less common symptoms of Noonan syndrome are briefly described below.
Learning difficulties
Around 10% of children with Noonan syndrome will have learning difficulties which are usually mild.
To put this in context, the average intelligence quotient (IQ) score is 100. The average IQ of children with Noonan syndrome affected by a learning difficulty is around 70.
Increased bruising or bleeding
Around 50% of children with Noonan syndrome have a defect that means that their blood does not clot properly. This makes their skin more vulnerable to bruising and they may bleed excessively from cuts.
If your child is affected and needs surgery or dental work, they will need to be observed for longer than usual afterwards, in case of bleeding.
Eye conditions
Around half of children with Noonan syndrome will have one or more eye conditions, including:
- a squints, where one eye does not look straight ahead but turns inwards, outwards, upwards or downwards
- astigmatism, where the cornea (the transparent layer at the front of the eye) is not a perfectly shaped curve, causing symptoms such as blurred vision
- lazy eye, where one eye is less able to focus than the other eye, leading to an increasing reliance on the more effective eye
Lymphatic problems
Children with Noonan syndrome will have problems with their lymphatic system. Most commonly this causes a build-up of lymph fluid in their feet resulting in severe swelling. This is known as lymphoedema.
Hypotonia
Hypotonia is decreased muscle tone, where the muscles take on a floppy, ‘rag-doll’ appearance. Most children with Noonan syndrome will have a degree of hypotonia, which may mean it takes them longer to reach developmental milestones during early childhood.
Hearing loss
Children with Noonan syndrome may experience temporary bouts of hearing loss. This is caused by a build-up of fluid inside the middle ear, which is known as Otitis media.
Infertility and undescended testicles
In around 60% of boys with Noonan syndrome, either one or both of their testes fails to descend into the scrotum (the bag that holds the testicles). It is important that this is corrected through surgery at an early age, to avoid reduced fertility in later life.
In addition, many older males who have not had early corrective surgery may have a reduced sperm count.
Feeding problems
Many babies with Noonan syndrome have feeding problems such as:
- sucking problems, due to weak muscles in the mouth and sometimes a high-arched palate
- a weak chewing action that can mean mealtimes take longer than expected
- projectile vomiting during or after meals
These sorts of feeding problems can cause babies to gain weight at a much lower rate than would usually be expected. This is often referred to as ‘failure to thrive’. However, feeding problems usually resolve once a child reaches two years of age.
Behavioural difficulties
Children with Noonan syndrome may sometimes show difficult behaviour, although it is not usually severe enough to need specialist help. Common types of difficult behaviour include:
- being unusually clumsy
- being a very fussy eater, for example, some children will refuse to eat certain flavours or textures of food
- persistent fidgetiness
- being very stubborn or irritable at certain times
- repeating sounds and words that are said by other people
Problems with bones and joints
Some children with Noonan syndrome will develop problems that affect normal development of bones and joints (orthopaedic problems). For example:
- Joint hypermobility, where joints have an unusually wide range of movement. This affects around half of children with Noonan syndrome.
- Abnormally curved spine (scoliosis). This affects a very small number of children with Noonan syndrome.
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Causes
Noonan syndrome is caused by a series of genetic mutations. A genetic mutation happens when the normal instructions that are carried in certain genes become ‘scrambled’. This means that some of the body’s processes will not work in the normal way.
There are four genetic mutations that have been linked to Noonan syndrome. They are:
- the PTPN11 mutation - which accounts for half of all cases
- the SOS1 gene mutation - which accounts for around 1 in 5 cases
- the RAF1 gene mutation - which accounts for around 1 in 7 cases
- the KRAS gene mutation - which accounts for around 1 in 10 cases
In an estimated 1 in 5 cases of Noonan syndrome no specific genetic mutation can be found.
The different mutations don't appear to cause different symptoms, with the following two exceptions:
- children with the PTPN11 gene tend to have pulmonary stenosis
- children with the RAF1 gene tend to have cardiomyopathy
Exactly how these genetic mutations trigger the symptoms of Noonan syndrome is still unclear. However, it is thought that they disrupt some of the proteins responsible for regulating cell growth and development.
These mutations can be inherited (autosomal dominant inheritance) or happen entirely by chance (sporadic mutation).
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 that is responsible for the condition is passed on 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 mutation occurs is not yet fully understood.
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Diagnosis
Noonan syndrome may be suspected if your GP or paediatrician (a doctor who specialises in the treatment of children) spots some of the signs and symptoms most commonly associated with the condition. These include:
- distinctive facial features
- a confirmed diagnosis of congenital heart disease
- short stature
- abnormalities of the bones of the chest
- a family history of Noonan syndrome
- mild learning difficulties
- undescended testicles
- lymphoedema (swelling of specific parts of the body as a result of a build-up of fluid)
However, in some cases, symptoms may not become apparent until the teenage years or adulthood.
You may be referred to a specialist (a clinical geneticist) for genetic testing. In most cases, Noonan syndrome can be confirmed by testing the blood for the various genetic mutations. However, in about 1 in 5 cases, no specific mutation can be found, so a negative blood test will not rule out Noonan syndrome.
Further testing
Once Noonan syndrome has been confirmed or is strongly suspected, further tests are needed to measure the extent and severity of the symptoms. These tests will probably include:
- an electrocardiograph (ECG) - where electrodes (small, metallic discs that are placed on the skin) are used to measure the electrical activity of the heart
- an echocardiogram - where sound waves are used to build up a detailed image of the various structures that make up the heart
- educational assessment if required
- blood tests for clotting studies if there is a history of bruising or bleeding
- sight tests - to check for problems such as squints or blurred vision
- hearing tests - to check for problems such as hearing loss that is caused by otitis media
The echocardiogram may need to be monitored regularly to determine if there is any progressive change in the heart function.
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Treatment
There is no cure for Noonan syndrome. However, it is possible to treat certain aspects of the disorder.
Congenital heart disease
A full assessment of your child's heart function should be carried out as soon as Noonan syndrome has been diagnosed. This will help determine the recommended treatment for your child’s congenital heart disease.
Pulmonary stenosis
In cases of pulmonary stenosis that are causing no or few symptoms, a policy of ‘watchful waiting’ may be recommended. This means that your child will receive no immediate treatment but their heart will be carefully monitored.
In more serious cases of pulmonary stenosis a small, flexible tube, known as a catheter, can be inserted to the site of the pulmonary valve. A small balloon is passed up through the catheter and inflated to widen the affected valve. This procedure is known as a balloon angioplasty. Once the valve has been widened, the balloon is removed. Sometimes a replacement valve is required.
Hypertrophic cardiomyopathy (HCM)
There are several treatments available for hypertrophic cardiomyopathy (HCM). The recommended treatment will depend on the extent and severity of your child’s symptoms and the general state of their heart. In most cases in Noonan syndrome it will be worse in infancy but improve with age. Possible treatments include using:
- medication, such as beta-blockers, to help stabilise the functions of the heart
- surgery to remove or destroy some of the excess heart muscle
Septal defects
As with pulmonary stenosis, watchful waiting is usually recommended for small septal defects. Many defects close by themselves as a child gets older.
In cases of mild to medium sized septal defects, it may be possible to seal the hole using a catheter. The catheter is guided to the site of the hole and then a specially designed mesh is passed through the catheter to seal it.
In cases of medium to large sized septal defects, open heart surgery will probably be required. This involves a patch being stitched directly over the hole.
Short stature
Your child’s size and growth rate will be regularly assessed throughout their childhood. If your child’s growth rate is thought to be seriously reduced, a course of human growth hormone (HGH) may be suggested.
A course of HGH usually starts at around five years of age and continues until adult height is reached. A type of HGH called somatropin is used to treat children with Noonan syndrome. Somatropin is given by a daily injection using an auto-injector syringe.
Most children are able to tolerate somatropin well and side effects are uncommon, with the exception of some temporary soreness, itchiness and redness at the site of the injection.
Feeding and speech problems
In children with Noonan syndrome, weak muscles in the mouth can sometimes cause speech and feeding problems. If your child has speech or feeding problems, they may be referred to a speech therapist for help and support.
The speech therapist will work with your child to help them develop the muscles in their mouth and they will show them how to use their muscles more effectively.
In particularly severe cases of poor feeding, your baby may need a feeding tube for a few months.
Undescended testicles
If you have a baby boy with an undescended testicle or testicles, corrective surgery will usually be recommended before he reaches the age of two.
A surgical procedure that is known as an orchidopexy is usually recommended to treat undescended testicles. It involves making a small cut in your child’s tummy and passing small surgical instruments through the incision. These instruments are used to move the testicle(s) into the correct position.
See Undescended testicles - treatment for more information.
Learning difficulties
If your child is diagnosed with learning difficulties, it does not necessarily mean that they cannot be taught in a mainstream school. However, children with more severe disabilities may benefit from attending a specialist school.
To ensure that your child gets the support that they need, it is recommended that a statement of special educational needs (SEN) is drawn up. An SEN is a type of care plan produced by both the child’s parents and their school, and is designed to meet the child’s educational requirements.
Other health conditions
Information about other health conditions that can sometimes affect people with Noonan syndrome and will require treatment is provided in more depth in a number of other topics. See the following for more information and advice:
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