The age at onset of puberty is often delayed and short stature is common in Noonan syndrome, although adult height is not always affected. In boys there may be problems with the testicles descending (cryptorchidism) and reduced fertility in adult life.


The average age of the onset of puberty is delayed in people with Noonan syndrome compared with the general population:

  • 35% of boys enter puberty after the age of 13·5 years
  • 44% of girls enter puberty after the age of 13 years.

Fertility is not impaired in women with Noonan syndrome.

In a significant number of boys with Noonan syndrome one or both testes may fail to descend into the scrotum (cryptorchidism). This should be corrected by early surgery which helps to reduce the incidence of fertility problems with lower sperm counts later.


At birth, the baby’s weight and body length are usually normal. But as the growth spurt that comes with puberty is often delayed or longer, short stature is common during the age of normal puberty. The adult height of people with Noonan syndrome is not always affected – but on average it is reduced.

It is useful to monitor growth and refer to the growth charts for Noonan syndrome where possible. If growth is significantly delayed it may be helpful to have a referral to a specialist paediatric endocrinologist. Although the level of growth hormone is usually normal children with short stature in Noonan syndrome will usually respond to treatment with regular growth hormone injections. There is some controversy about this as the treatment will be required over several years and is expensive. Most children with Noonan syndrome will get an increase in height from the treatment which may be very helpful in boosting the child’s self-confidence. However there is still some debate about how effective the growth hormone treatment is in increasing the final height.

At the present time growth hormone is only available through a specialist paediatric endocrinologist. The NHS has not recommended growth hormone for all children with Noonan Syndrome but the position on this is currently under review. The presence of an underlying cardiomyopathy may be a contraindication for growth hormone as there have been reports of cardiomyopathy increasing on growth hormone treatment

Other growth-related issues include spinal deformity, chest deformities (‘pigeon chest’ or a sunken chest), widely spaced nipples, forearms that angle away from the body to a greater degree than normal when fully extended (cubitus valgus), and knock knees.


  • Shaw AC, Kalidas K, Crosby AH, Jeffery S, Patton MA. The natural history of Noonan syndrome: a long-term follow-up study. Arch Dis Child. 2007 Feb;92(2):128-32. doi: 10.1136/adc.2006.104547.
  • Roberts AE, Allanson JE, Tartaglia M, Gelb BD. Noonan syndrome. Lancet. 2013;381(9863):333-342.

Hearing and vision

People with Noonan syndrome can suffer from hearing loss and eye problems.


Problems with hearing are relatively common, but in many cases these are related to fluid in the middle ear (chronic otitis media) in childhood and are temporary. Severe hearing problems are rare but may be helped with hearing aids or cochlear implants.


Eye problems that may affect people with Noonan syndrome include:

Strabismus – a condition where the eyes do not point in the same direction. Also known as a squint, the condition causes one or both eyes to turn inward (‘crossed eyes’) or outward (‘wall eyes’).

Refractive errors – a type of visual problem that makes it hard to see clearly. They occur when the shape of the eye keeps light from focusing correctly on the retina (a light-sensitive layer of tissue in the back of the eye). It is corrected by glasses.

Amblyopia – also known as a ‘lazy eye’, amblyopia is a childhood condition where the vision does not develop properly because one or both eyes are unable to build a strong link to the brain. It usually only affects one eye, and means that the child can see less clearly out of the affected eye and relies more on the ‘good’ eye. It is treated by patching the eye.

Nystagmus – a condition of uncontrolled eye movement that causes the eyes to move or “wobble” constantly.


  • Qiu WW, Yin SS, Stucker FJ. Audiologic manifestations of Noonan syndrome. Otolaryngol Head Neck Surg. 1998 Mar;118(3 Pt 1):319-23.
  • van Trier DC, van Nierop J, Draaisma JMT, van der Burgt I, Kunst H, Croonen EA, Admiraal RJC. External ear anomalies and hearing impairment in Noonan Syndrome. Int J Pediatr Otorhinolaryngol. 2015 Jun;79(6):874-878.
  • Roberts AE, Allanson JE, Tartaglia M, Gelb BD. Noonan syndrome. Lancet. 2013;381(9863):333-342.


People with Noonan syndrome show a slight increase in risk of having seizures. These do not seem to have a particularly different pattern from other forms of epilepsy, although there is some evidence of non-epileptic or dissociative seizures occurring.

Epilepsy is a major clinical issue in cardiofaciocutaneous (CFC) syndrome when it is caused by the BRAF gene. Seizures have been estimated to occur in between 15–50% of patients with BRAF mutations, and may be severe and associated with changes on the brain MRI scan. The treatment may involve several anticonvulsants.


Lymphatic disorders are a well-recognised complication of Noonan syndrome. They can lead to swelling, due to the accumulation of fluid in the body.

The lymphatic system is a network of channels and glands throughout the body that helps fight infection and remove excess fluid. It drains extra fluid – lymph – that has passed out of the blood and into tissues and returns it back to the blood. Issues with the lymphatic system can lead to oedema – an excess of watery fluid collecting in the body’s tissues or cavities.

Before birth (prenatal)

Abnormalities in development of the lymphatic system can become apparent during pregnancy. The prenatal issues for Noonan Syndrome are:

  • Increased nuchal translucency Between 10 and 14 weeks of pregnancy, ultrasound is used to measure the size of the translucent space behind the neck of the foetus – the nuchal translucency. The size reflects the amount of fluid that has accumulated under the skin of the foetus. Nuchal translucency tends to be increased in Noonan syndrome, as well as in other chromosome disorders such as Down syndrome and Turner syndrome.
  • Hydrothoraces: Accumulation of fluid in the pleural cavity (the space between the lungs and the walls of the chest) of the foetus.
  • Hydrops fetalis: Abnormal fluid collections in the foetus, such as around the heart or lungs, in the abdomen, or in the skin and soft tissues.)

Children and adults

Swelling of the feet at birth is often described in Noonan syndrome, and some of the characteristics of this condition – webbed neck, low-set ears, low hairline and drooping of the upper eyelid (ptosis) – may be related to oedema in the womb.

Persistent lymphatic disorders are rare, however. When they do occur, they can affect:

  • Legs: Lymphoedema is a long-term (chronic) condition that causes swelling in the body’s tissues. In Noonan syndrome it usually affects the legs, so is termed bilateral lower limb lymphoedema.
  • Genitals: Swollen genitals can be caused by the backflow of chyle (a milky fluid containing fat droplets which drains from the small intestine into the lymphatic system during digestion). If the valves in the lymphatic system do not control the flow correctly, chyle can mix with lymph and be routed into the genitals and legs. This is called chylous reflux.
  • Small intestine: Enlarged lymph vessels supplying the lining of the small intestine can lead to a range of problems, including
  1. Swelling of the legs and abdominal discomfort
  2. Loss of lymphatic fluid into the intestine
  3. Leaking of albumin and other protein-rich materials into the         intestine (called protein-losing enteropathy)
  4. Too little albumin in the blood
  5. Reduced levels of antibodies
  6. Immunodeficiency (called intestinal lymphangiectasia).
  • Chest: Lymphatic fluid can leak into the space between the lung and chest wall. When this fluid builds up in the lungs, it can cause a severe cough, chest pain and difficulty breathing. The condition is termed chylothorax.

The age of onset of these problems varies – for some, swelling begins as a young child, for others as adults.

The causes of these issues in people with Noonan Syndrome are not fully understood. It is not clear whether the primary problem is an abnormality of the valves in the lymphatics and veins, or whether the reflux in the legs and genital region is a result of the chylous reflux from the intestines.

It is also not clear why this may present later in life – the triggers are not known.

Specialist Tests

A technique called lymphoscintigraphy is used to investigate lymphoedema. A radiolabelled tracer is injected, which then allows an image of the lymph drainage pathways to be created using a gamma camera.

Management and treatment

Compression garments and bandaging are used to help reduce swelling of the legs, and a low fat diet or cryotherapy may be effective in reducing swollen genitals.

In 2020, US doctors reported that a Noonan syndrome patient with severe lymphatic issues had been treated successfully with trametinib (an inhibitor of mitogen-activated protein kinase, a component of the Ras/MAPK pathway).


  • Joyce S, Gordon K, Brice G, et al. The lymphatic phenotype in Noonan and Cardiofaciocutaneous syndrome. Eur J Hum Genet. 2016;24(5):690-696.
  • Dori Y, Smith C, Pinto E, Snyder K, March ME, Hakonarson H, Belasco J. Severe Lymphatic Disorder Resolved With MEK Inhibition in a Patient With Noonan Syndrome and SOS1 Mutation. Pediatrics. 2020 Dec;146(6)

Musculoskeletal pain is a frequent and under-recognised clinical feature of Noonan syndrome.

A 2021 study found that 25% of people with Noonan syndrome suffered from musculoskeletal pain, and 14% had joint stiffness in the wrists, elbows, ankles, knees and hips.

A separate study, also in 2021, found that 62% of people with Noonan syndrome experienced chronic pain. This pain was present among both adults and children – in this study, 50% of the people with chronic pain were children, less than 16 years old – and was linked to hypermobile joints. Joint laxity is more common in people with Noonan syndrome – a 2012 study reported that it affected 49% of people with Noonan syndrome, a portion of whom had chronic pain. If joints are hypermobile, the abnormal range of motion can increase stress on adjacent muscles and tendons, causing pain.

Although hypermobility may be an important factor the pattern of joint involvement is different from that seen with hypermobility alone and it is not clear what other mechanisms may be involved with Noonan syndrome. On investigation there are no abnormalities of the inflammatory markers seen in other forms of arthritis and fortunately although the pain may be distressing there is no progressive joint damage.


  • Le Quellec A, Edouard T, Audebert-Bellanger S, Pouzet A, Bourdet K, Colson C, Oriot C, Poignant S, Saraux A, Devauchelle-Pensec V. Joint involvement in Noonan syndrome. A retrospective paediatric descriptive study. Joint Bone Spine. 2022 Jan;89(1):105270. doi: 10.1016/j.jbspin.2021.105270. Epub 2021 Sep 14. PMID: 34534690.
  • Vegunta S, Cotugno R, Williamson A, Grebe TA. Chronic pain in Noonan Syndrome: A previously unreported but common symptom. Am J Med Genet A. 2015 Dec;167A(12):2998-3005. doi: 10.1002/ajmg.a.37337. Epub 2015 Aug 22. PMID: 26297936.
  • Smpokou P, Tworog-Dube E, Kucherlapati RS, Roberts AE. Medical complications, clinical findings, and educational outcomes in adults with Noonan syndrome. Am J Med Genet A. 2012 Dec;158A(12):3106-11. doi: 10.1002/ajmg.a.35639. Epub 2012 Nov 19. PMID: 23165751.

Intellectual Development, Behaviour & Education

People with Noonan syndrome show a wide range of intellectual development, but some children may be slower in their developmental milestones and need extra help at school

The majority of people with Noonan syndrome have an IQ within the normal range but more children fall into the low-average range than the general population. In some cases, especially where there is an overlap with the CFC syndrome, there may be moderate to severe intellectual disability.

In both children and adults, difficulties with language are more common than in the general population. These can include problems with reading and spelling (dyslexia), and so some children with Noonan syndrome perform more poorly in tests of verbal ability than in tests of non-verbal ability. They can also have difficulties in explaining the meaning of words – which relies on overall reasoning ability and on vocabulary. In addition there may be problems with numeracy.
Behavioural and emotional problems
Children with Noonan syndrome are more likely to display social and emotional problems than their peers. In particular, they can tend to be inattentive. Some can find it difficult to express emotions verbally, and other issues such as mood disturbances, communication difficulties, attention deficit/hyperactivity disorder, and difficulties with social interaction have also been reported (e.g autism). The teenage years may be difficult for any child but especially so in Noonan syndrome as they may have difficulty fitting in with their peer group as they are shorter, later in entering puberty and may have some educational problems.
Motor coordination
Parents often report that their children are ‘clumsy’, and children with Noonan syndrome do have a higher incidence of suspected developmental coordination disorder than their peers.

Older children tend to have fewer problems than younger ones – clumsy children learn to adapt and manage their clumsiness but the underlying motor difficulties remain. Referral to physiotherapy and practice in specific skills, such as writing, might lead to improvements.
As children with Noonan syndrome are usually of shorter stature than their peers, it might be proposed that this would affect their self-esteem – in the same way that it seems to in other disorders with short stature. However, this is not always the case and some children with Noonan syndrome can be very self-confident. Strong parental support will help to improve the child’s confidence.
Educational achievement varies. Many gain a GCSE or equivalent qualification, but a significant proportion with more marked difficulties do not attain a qualification.

A study in 2007 found that:

  • 43% gained a GCSE
  •  8% gained an A Level
  • 16% had a higher educational qualification
  • About a third of adults had attended a school for children with learning difficulties.
  • 20% attended a mainstream school but needed extra help.
  • Of those adults who were no longer in school, 60% had a full-time job.

It is important that any affected child with delay in development should have an educational assessment at the start of their schooling. This will help families find the best placement for their child and may bring additional input from a speech therapist or classroom assistant.


  • Lee DA, Portnoy S, Hill P, Gillberg C, Patton MA. Psychological profile of children with Noonan syndrome. Dev Med Child Neurol. 2005 Jan;47(1):35-8.
  • Shaw AC, Kalidas K, Crosby AH, Jeffery S, Patton MA. The natural history of Noonan syndrome: a long-term follow-up study. Arch Dis Child. 2007;92(2):128-132.
  • Roberts AE, Allanson JE, Tartaglia M, Gelb BD. Noonan syndrome. Lancet. 2013;381(9863):333-342.


Noonan Syndrome is a genetic disorder – a change in a gene causes disruption in one of the pathways that guides the development and growth of the body.

Noonan syndrome is caused by a fault in one of several genes. The commonest gene involved is called PTPN11 but there have now been around 15 genes discovered which may cause Noonan syndrome or a related disorder. Genetic testing can be used to confirm the diagnosis of Noonan syndrome and also to test for the condition in pregnancy.


The first clinical description of what we now term Noonan Syndrome is thought to have been published by Estonian student Oskar Kobyliński in 1883. While a student at the University in Dorpat (now Tartu, Estonia), he reported on a patient with a webbed neck, which he termed ‘flüghautige Verbreitung des Halses’ (wing-like extension of the neck). This was followed by descriptions of similar cases in 1902 and 1930.

In 1962, at the Midwest Paediatric Research Meeting, Dr Jacqueline Noonan presented a clinical study of nine children who had congenital heart disease as well as other anomalies. The nine patients – six males and three females – shared distinctive facial features and had a short stature, pulmonary stenosis (problems with a major heart valve) and significant chest deformities. She published her research on these nine and an additional ten patients in the American Journal of Diseases of Children in 1968.

As Dr Noonan was the first to indicate that this condition occurs in both sexes, can be inherited in certain cases, includes congenital heart defects and is associated with a normal number of chromosomes, the eponym Noonan syndrome was proposed.

Thickening of the heart muscle (hypertrophic cardiomyopathy), which occurs in some patients with Noonan syndrome, was first described in 1972.

Research on the genetics of Noonan syndrome often looked at the X chromosome, as people with Turner syndrome – which results from a single X chromosome only, rather than the usual XX or XY chromosomes – and Noonan syndrome have some similar physical characteristics. (Indeed, in 1938 the term ‘male Turner syndrome’ had been proposed, causing some confusion.). But in 1994, a link between Noonan syndrome and chromosome 12 was found.

In 2001, this link was narrowed down to a genetic change – a mutation – in the PTPN11 gene on chromosome 12, present in about half of patients with Noonan syndrome. Since then, other genes have been found to be associated with Noonan syndrome.
In the majority of people with the condition – about 60% – Noonan syndrome is caused by a new genetic change in the egg or sperm and so there is no family history. In this case, the chance of the parents having another child with Noonan syndrome is very small. This is termed ‘sporadic’ as it is caused by a ‘new mutation’.

In some people, however, the faulty gene associated with Noonan syndrome is inherited from one parent – who may or may not have obvious features of the condition themselves. Only one parent needs to carry the fault to pass it on, and each child they have has a 50% chance of being born with the condition. This type of inheritance is called ‘autosomal dominant’.

There is a very rare ‘autosomal recessive’ form of Noonan syndrome. This involves two parents who do not have the condition each having a particular faulty gene (LZTR1). In this case, Noonan syndrome may occur if a child inherits two copies of the faulty gene – one from each parent.

The genes

The most common genetic cause of Noonan syndrome is a mutation in a gene called PTPN11. This was discovered in 2001 and, since then, other genes have been linked to the condition.

  • A mutation in PTPN11 occurs in about 50% of people with Noonan syndrome.
  • SOS1 is the second most common causative gene, with variants occurring in 16–20% of individuals without PTPN11 variants.
  • Mutations in other genes – RAF1, RIT1, KRAS, NRAS, BRAF, MAP2K1, RRAS, RASA2, SOS2, LZTR1 – are less common causes.
  • In about 5–10% of cases, the genetic cause of Noonan syndrome is still not known.

The genes associated with Noonan syndrome play a crucial role in the Ras-mitogen-activated protein kinase (Ras/MAPK) pathway, which is involved in the development and growth of cells in the body. Several other syndromes are also associated with the Ras/MAPK pathway; collectively, the group of syndromes are known as the RASopathies [link to page on RASopathies] and they share many similar features.


  • Tartaglia M, Kalidas K, Shaw A, et al. PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity. Am J Hum Genet. 2002;70(6):1555-1563.
  • Johnston JJ, van der Smagt JJ, Rosenfeld JA, et al. Autosomal recessive Noonan syndrome associated with biallelic LZTR1 variants. Genet Med. 2018;20(10):1175-1185.
  • Roberts AE, Allanson JE, Tartaglia M, Gelb BD. Noonan syndrome. Lancet. 2013;381(9863):333-342.
  • Noonan Syndrome—Historical Awareness and Genetic Issues. Published Online: June 6th 2011. US Endocrinology, 2008;4(2).
  • Marcinowski F. Oskar Kobyliński (1856-1926) and the first description of Noonan syndrome in the medical literature. J Med Biogr. 2020 Nov;28(4):202-207. 72018783379. Epub 2018 Jul 12. PMID: 29998749.

Feeding difficulties

Many infants with Noonan syndrome have feeding difficulties which tend to improve with age.

Most infants with Noonan syndrome have feeding difficulties. This can include poor sucking, longer feeding times, or repeated vomiting. About a quarter of infants need to be fed by a tube for 2 weeks or longer. Reflux is also common. A speech therapist is the best person to assess and treat the feeding difficulties. X rays may be taken to observe the swallowing but the cause is likely to be a problem with the development of swallowing rather than any mechanical blockage. The feeding problems usually resolve by the age 15 months, but in a few cases feeding difficulties may persist for longer.

Feeding difficulties in infancy can also be an indication of delayed language development and lower educational achievement in the long-term.


  • Shaw AC, Kalidas K, Crosby AH, Jeffery S, Patton MA. The natural history of Noonan syndrome: a long-term follow-up study. Arch Dis Child. 2007;92(2):128-132.
  • Roberts AE, Allanson JE, Tartaglia M, Gelb BD. Noonan syndrome. Lancet. 2013;381(9863):333-342.

Facial features

People with Noonan syndrome have characteristic facial features, particularly during childhood, which change with age and may be insignificant in adult life. In early childhood, ptosis (drooping eyelids), low set ears, short neck, and low hairline are characteristic.

The facial features include:

All ages

  • Eyes: May be strikingly blue eyes with arched or diamond-shaped eyebrows
  • Ears: Low set, posteriorly rotated, thick helices

Newborn baby (Features can be subtle or absent)

  • Forehead, face, hair: Tall forehead, low posterior hairline
  • Eyes: Widely spaced eyes, drooping eyelids (ptosis), epicanthal folds (skin fold of the upper eyelid covering the inner corner of the eye)
  • Nose: Short and broad, depressed root, upturned tip
  • Mouth: Deeply groove between the mouth and nose (the philtrum), small lower jaw (micrognathia)
  • Neck: Excessive skin at the back of the neck

Infancy (2–12 months)

  • Forehead, face, hair: Large head, tall and prominent forehead
  • Eyes: Widely spaced eyes, drooping of the upper eyelid , or thick-hooded eyelids
  • Nose: Short, wide, depressed nasal root

Childhood (1–12 years)

  • Forehead, face, hair: Features might appear coarse, triangular face
  • Neck: Webbing may be obvious

Adolescence (12–18 years)

  • Forehead, face, hair: Expressionless face
  • Nose: Bridge is high and thin
  • Neck: Webbing may be obvious

Adulthood (>18 years)

  • Forehead, face, hair: Distinguishing facial features are subtle, skin appears thin and transparent
  • Nose: Prominent nasolabial fold

A 2017 study used facial analysis technology to examine 161 people with Noonan syndrome from 5 different global populations – Caucasian, African and African American, Asian and Latin American. They found that the facial features were very similar across all the populations, and the technology could diagnose patients from all population groups with a sensitivity and specificity of 88% and 89%, respectively. The researchers proposed that the technology could support clinicians in making accurate Noonan syndrome diagnoses, helping with earlier detection and increased recognition of the syndrome throughout the world.


  • Roberts AE, Allanson JE, Tartaglia M, Gelb BD. Noonan syndrome. Lancet. 2013;381(9863):333-342.
  • Kruszka P, et al. Noonan syndrome in diverse populations. Am J Med Genet 2017; 173(9):2323-2334.
  • Hammond P, et al. 3D analysis of facial morphology. Am J Med Genet 2004;126A(4):339–348.
  • Illustrations Courtesy: National Human Genome Research Institute (NHGRI): National Human Genome Research Institute


People with Noonan syndrome have a small increased risk of several blood-related (haematological) cancers.

The genes involved in Noonan syndrome are part of the RAS/MAPK pathway, which controls cell growth. Mutations in these genes which are present at birth and occurred in egg or sperm (germinal mutations) such as in Noonan Syndrome are not usually associated with cancer. However when they occur due to a genetic error in the body after birth (somatic mutations) they may lead to a local cancers. Because somatic mutations of these genes may cause cancer they have been studied extensively by the pharmaceutical industry and there are many drugs in the pipeline which block the RAS/MAPK pathway and could potentially have application for treatment in Noonan syndrome.

As has been said cancer is very rare in Noonan syndrome but one specific form of leukaemia has been reported

  • Juvenile myelomonocytic leukaemia is a very rare childhood blood cancer that occurs when immature blood cells (called blasts) make too many myelocytes and monocytes (two types of white blood cells) and cause a form of leukaemia. Fortunately there is now good treatment for this condition in specialised centres.

There are long term follow up studies being carried out to investigate whether people with Noonan syndrome have a higher incidence of other cancers in later life, but at present there is no evidence for this.


  • Roberts AE, Allanson JE, Tartaglia M, Gelb BD. Noonan syndrome. Lancet. 2013;381(9863):333-342.
  • Strullu M, et al. Juvenile myelomonocytic leukaemia and Noonan syndrome. J Med Genet. 2014 Oct;51(10):689-97.
  • Jongmans MC, van der Burgt I, Hoogerbrugge PM, et al. Cancer risk in patients with Noonan syndrome carrying a PTPN11 mutation. Eur J Hum Genet. 2011;19(8):870-874.

Cardiology – heart issues

Cardiac or heart abnormalities are often associated with Noonan syndrome. These can include problems with the heart valves, holes in the walls separating the chambers of the heart, and thickening of the heart muscle.

People with Noonan syndrome can be affected by a wide range of heart-related disease, which fall into two main categories:

  • Congenital heart disease affects about 80% of patients
  • Thickened heart muscle (hypertrophic cardiomyopathy) is found in about 20% of patients.

Heart problems in Noonan syndrome


Pulmonary valve stenosis
The pulmonary valve (the valve between the right ventricle and the pulmonary artery that goes to the lungs) is too small, narrow, or stiff.

Moderate risk:

Hypertrophic cardiomyopathy
The heart muscle becomes abnormally thick (hypertrophied).


Atrial septal defect
A hole in the wall (septum) that divides the upper chambers (atria) of the heart.
Ventricular septal defect
A hole in the wall (septum) that separates the two lower chambers (ventricles) of the heart
Atrioventricular septal defect
A large defect in the centre of the heart that can be a combination of:

  • atrial septal defect
  • ventricular septal defect
  • abnormalities of the valves, often resulting in one large valve instead of two separate valves

Mitral abnormalities
A problem with the valve located between the left heart chambers (left atrium and left ventricle)

Aortic coarctation
Part of the aorta – the large artery that carries oxygen-rich blood to the rest of the body – is narrower than usual.

Patent ductus arteriosus
A persistent opening between the two major blood vessels leading from the heart. The opening, a normal part of a baby’s circulatory system in the womb, usually closes shortly after birth.

Tetralogy of Fallot
Complex abnormality with four defects of the heart:

  • Ventricular septal defect;
  • Pulmonary stenosis;
  • Enlarged and abnormal aortic valve;
  • Ventricular hypertrophy – the muscular wall of the lower right chamber of the heart (right ventricle) is thicker than normal.

Pulmonary valve stenosis

Affecting about 40% of people with Noonan syndrome, pulmonary valve stenosis is the most common heart problem. It occurs when the pulmonary valve (the valve between the right ventricle and the pulmonary artery that goes to the lungs) is too small, narrow, or stiff.

The severity varies:

  • Mild cases (about 60%): these cases are similar to patients with pulmonary valve stenosis who do not have Noonan syndrome – the stenosis tends not to progress (and often improves without treatment) and may not need surgical treatment. However, in some cases there may be an additional heart problem such as an atrial septal defect.
  • Moderate (about 10%) or severe (about 30%) cases: in these cases, the rates of surgical treatment are higher – about 50% and 100%, respectively.

Atrioventricular septal defects

An atrioventricular septal defect (AVSD) is a large defect in the centre of the heart that can be a combination of:

  • atrial septal defect
  • ventricular septal defect
  • abnormalities of the valves, often resulting in one large valve instead of two separate valves

A partial atrioventricular septal defect is the most common form of this problem, but complete defects, while rare, do occur.

Hypertrophic cardiomyopathy

About 10 – 20% of people with Noonan syndrome suffer from hypertrophic cardiomyopathy, where the heart muscle becomes abnormally thick (hypertrophied). This can become evident early in life, with more than half diagnosed by six months of age (much earlier than other childhood forms of hypertrophic cardiomyopathy, which on average become evident at the age of 8 years). Obstructions of the outflow from the left ventricle are common, and children with Noonan syndrome and hypertrophic cardiomyopathy are more likely to have congestive heart failure than other children with hypertrophic cardiomyopathy.


A mutation in the PTPN11 gene is the most common cause of Noonan syndrome but there are now up to 15 genes which may be involved. The gene affected can also influence the likelihood and type of congenital heart disease.

PTPN11 mutation

  • More likely to have pulmonary valve stenosis or an atrial septal defect
  • Less likely to have hypertrophic cardiomyopathy

RAF1 mutation

  • Less likely to have pulmonary valve stenosis
  • More likely to have hypertrophic cardiomyopathy

RIT1 mutation

  • More likely to have hypertrophic cardiomyopathy and valve abnormalities

SOS1 mutation

  • More likely to have pulmonary valve stenosis


About a third of patients with pulmonary stenosis needed surgery or a repeat procedure.

A balloon can be used to open a stiff valve, through a procedure termed ‘percutaneous balloon valvuloplasty’. If this fails or is deemed not feasible, surgical valvotomy – an open-heart procedure to open up a valve – can be carried out.

Other structural heart defects may require invasive treatment. Some may be amenable to catheter intervention (e.g. percutaneous balloon valvuloplasty, stent insertion or device closure) but others may require cardiac surgery. Treatment of other structural heart defects – these may require cardiac surgery

Treatment of hypertrophic cardiomyopathy is primarily directed at treating symptoms. This is usually with medication (e.g. beta blockers), although rarely cardiac surgery to relieve left ventricular outflow tract obstruction or to repair or replace the mitral valve may be required. Very rarely, individuals with Noonan syndrome and hypertrophic cardiomyopathy may be at an increased risk of potentially life-threatening abnormal heart rhythms and treatment with an implantable cardioverter-defibrillator (ICD) may be recommended. More recently, a new class of drugs (MEK inhibitors such as trametinib) has been reported to improve the features and symptoms of hypertrophic cardiomyopathy in some children with Noonan syndrome and related conditions presenting with very severe forms in the first few months of life. Further studies to investigate the use of these drugs are ongoing.


  • Linglart L, Gelb BD. Congenital heart defects in Noonan syndrome: Diagnosis, management, and treatment. Am J Med Genet C Semin Med Genet. 2020;184(1):73-80.
  • Burch M, Sharland M, Shinebourne E, Smith G, Patton M, McKenna W. Cardiologic abnormalities in Noonan syndrome: phenotypic diagnosis and echocardiographic assessment of 118 patients. J Am Coll Cardiol. 1993 Oct;22(4):1189-92.
  • Roberts AE, Allanson JE, Tartaglia M, Gelb BD. Noonan syndrome. Lancet. 2013;381(9863):333-342.
  • Gelb BD, Roberts AE, Tartaglia M. Cardiomyopathies in Noonan syndrome and the other RASopathies. Prog Pediatr Cardiol. 2015;39(1):13-19.

The most common blood disorders are abnormalities of bleeding caused by coagulation defects.

A history of abnormal bruising or bleeding is common in people with Noonan syndrome, and some may have deficiencies of clotting factors in the coagulation pathway that leads to appropriate clotting and stopping blood loss. The reason for this is unclear.

A study of 72 people with Noonan syndrome found:

  • 65% had a history of abnormal bruising or bleeding
  • 40% took longer for blood clots to form
  • 50% had a single deficiency in the coagulation pathway
  • 17% had multiple deficiencies in the coagulation pathway

People with Noonan syndrome have also been found to have von-Willebrand disease – another condition where blood clots do not form correctly – and disorders related to platelets, which are cells in the blood which clump together at the start of clotting.

Although problems rarely occur, before an operation it is important that the surgical team is aware of the potential to bleed. This should lead to a careful coagulation scree before major surgery and in the case of minor day surgery the child may be kept overnight or at least until it is clear that any post operative bleeding has stopped.


  • Sharland M, Patton MA, Talbot S, Chitolie A, Bevan DH. Coagulation-factor deficiencies and abnormal bleeding in Noonan’s syndrome. Lancet. 1992 Jan 4;339(8784):19-21.
  • Linglart L, Gelb BD. Congenital heart defects in Noonan syndrome: Diagnosis, management, and treatment. Am J Med Genet C Semin Med Genet. 2020;184(1):73-80.

My daughter, son-in-law, and I suspect my 5-year-old grandson have Noonan’s Syndrome. It was ruled out by a blood test when he was 2, but he has so many markers and nothing else has been found that matches his collection of issues. He has been held back a year from starting school because of his developmental delay. Have you any advice as to who we could go to for further exploration? Is he too young for a cardiac ultrasound to be useful in picking anything up? If so, what age would be appropriate?

The best thing is to get a referral from your GP to the nearest Genetic Clinic. With the concerns about developmental delay, it would be appropriate to do some more general tests, e.g. a detailed chromosome test (chromosome microarray). Most children with Noonan Syndrome have a heart murmur which leads to a detailed scan. The scan can be done at any age, but without a murmur is probably going to be normal. The genetic testing for Noonan Syndrome has changed as more genes have been found, and it is possible the original test only looked at one of the genes, so may be worth repeating.

My brother has Noonan Syndrome and as I’m currently pregnant, I’m concerned about the likelihood of me or my unborn child carrying the faulty gene. What’s the chance of my brother’s siblings carrying the Noonan gene and passing it to their children?

Noonan Syndrome is a genetic condition, but most cases arise because of a chance change in the gene in the egg or sperm going to form them. If you have none of the features of Noonan Syndrome, then it is unlikely that you have inherited it. The best way to resolve this would be for your brother to be tested, and when the genetic change is identified in him you could be tested for this—if you have not inherited it, then you would not pass it on in the pregnancy.

I don’t know what stage you are at in the pregnancy, but the local genetic service would see you as an emergency and sort his testing out for you. You could get a referral to the local genetic service, either through your GP or your midwife. It is important they know you are pregnant if they are going to see you quickly.

Our son with Noonan’s hadn’t put any weight on for 2 years, although he is growing. The dietician had said to put him on a high calorie diet, basically to give him as much fat as possible. Was this the best thing to do?

Usually the first and most crucial question when a child’s weight isn’t increasing is whether the child is growing. Many young people with Noonan Syndrome are lightly built. There are many issues to consider with diet, as a balanced diet is usually preferred and there is also the issue of the lymphatic function in coping with fatty foods which can be compromised in some people with Noonan’s.

There is a possibility that my nine year old grandson will be offered growth hormone treatment. I believe it is a fairly new approach for Noonan’s children. Is there any information or contacts you could provide?

The use of growth hormone has now been approved by NICE for Noonan Syndrome, and they recommend its use from when the child is 4 years old. Their updated guidelines are here: You might also want to look at the NovoNordisk ‘More than Height’ website, which contains information about children taking growth hormone for NS: NovoNordisk is the pharmaceutical company that makes the growth hormone.

We held a webinar in October 2021 which covered growth hormone and treatments for children with NS.  Our guest speaker, Professor Mahel Dattani, is a paediatric endocrinologist at Great Ormond Street Hospital. A recording of this webinar can be found on our website.

I am a SENCo at a primary school and we have a child in year 5 with Noonan’s Syndrome. I was wondering if you could provide me with support or advice on how best to educate her on what to expect in puberty and teenage years?

We aren’t aware of any specially adapted resources in primary school in preparing for puberty (only the standard resources given to all children). In preparing for secondary school, if she has learning difficulties and/or autism and you feel she needs a more simplified version of puberty education, her mum could ask for this at the EHCP annual review and the school should be able to provide it. There are also sexual health charities who can support, such as Dhiverse, who have a programme for children (aged 11+) with learning difficulties or autism called ABC: They produce a free booklet and a leaflet which is more simplistic with pictures and they run a workshop programme. You would need to search online to find something similar in your area. Mencap also produce a guide (Sexuality and Relationships Resources) which contains information and links that might be useful.

Girls with Noonan’s Syndrome tend to have delayed puberty and start their periods later. This is less so if they’re taking growth hormones, but even with those they will start their periods later than their peers, which could potentially cause stress if she doesn’t realise beforehand that this will most likely be the case. NS girls also tend to have heavy periods because of problems with blood clotting. There are options to deal with this that her mother could discuss with her GP if it causes issues with her school attendance and/or participation in activities.

My son is 8 years old and has Noonan Syndrome. I have been trying to get a referral for him to see a specialist for 4 or 5 years. He isn’t registering on the normal height chart at the moment, and we just want to see someone. Has NICE approved the growth hormone treatment? This may help us to get a referral, as we have been told because it isn’t NICE approved, we can’t see a paediatric endocrinologist at all.

I don’t think NICE has made a specific recommendation yet. They do have a website which lists the new areas of guidance, so it is possible to watch that and we will put it on the website as soon as we hear as well.

It sounds as though you are being followed up by a paediatrician who is putting the growth measurements on a chart—that is always the first thing to do and helps guide the treatment. It sounds as though your son is at the bottom of the centile chart, and a referral to a paediatric endocrinologist to investigate and exclude other causes of poor growth such as low growth hormone might still be helpful even if growth hormone is not available at present. Are you able to discuss this with your paediatrician?

My 8-month-old daughter has been diagnosed with Noonan Syndrome. What can we do about feeding and what type of formula milk is appropriate?

It would be helpful if you could have a follow-up assessment from a paediatrician. They can monitor the growth. Most children with Noonan Syndrome will have slower growth. There is usually no need to have any special baby feeds, but if there are difficulties getting your child to feed it may be helpful to have some guidance from the paediatrician or a speech therapist.

We have a little girl who’s nearly 3 and she often complains she gets very hot. She’s always fanning herself and I’ve read a few things on temperature regulation. Is there any research on this? Is it related to the lymphatic system or could it be dealt with by diet? I’ve noticed she often gets this and she sweats a lot at night and we often feed her by tube when she’s in bed and she really sweats. I wondered whether that’s to do with fat in the diet?

I don’t know of any research but sweating at night is very common. I saw a child with Noonan Syndrome aged 10 yesterday and he sweats a lot and needs pyjamas changed. I think it’s common but we don’t know what causes it. We know that this is extremely common in children with Costello Syndrome and it tends to improve with age.

I am a 56-year-old adult male with Noonan Syndrome. What, if any, effect might the condition have on me as I get older?

In general terms, the main issue is the narrowing of the pulmonary valve in the heart in childhood which may recur again after treatment later in life. There are a number of rarer complications that may occur, but as you have mentioned no symptoms they are unlikely. The rare complications include swelling of the legs, problems with the gut, weight loss, and disturbances in the heart pumping or heart rhythm.

Can my daughter who has NS (PTPN11) and HC have her ears pierced?

I would seek the advice of her cardiologist. In our practice, HCM is not a contraindication to ear piercings but there may be other heart lesions (e.g. leaky valves) that may mean the cardiologist would want to be a bit more cautious.

I have a 13-year-old daughter with quite mild Noonan Syndrome, but I am concerned she may have some learning difficulties and anxiety issues. A speech therapist has assessed her and is happy she is okay, but I am not so sure. Is this a trait of Noonan Syndrome?

You should ask your GP for a referral to a clinical psychologist so your daughter can get an appropriate assessment. If your daughter is already under the care of a specialist, such as an endocrinologist or a paediatrician, it might be faster and more effective to ask them to refer her instead. If not, then the GP or even your daughter’s school should support in getting her properly assessed.
Learning difficulties can be an issue for many Noonan Syndrome youngsters, so this is something to discuss with your GP, daughter’s school and/or specialist if you have one. Anxiety can stem from a range of issues, so whilst this might relate to NS issues, it isn’t a clinical feature of the syndrome itself. The best thing would be to get your daughter seen by a specialist who can look at her full medical history and make a considered assessment.

Our 25-year-old son with Noonan Syndrome is on testosterone therapy in the form of monthly injections. During his transition from childhood to adulthood, he received various treatments (topical gel, oral capsules, monthly injections) but since he’s been on the monthly injections, we’ve noticed a significant adverse change in his behaviour. From previously being a happy, contented and sociable young man, he has become increasingly aggressive, argumentative, sullen, is behaving inappropriately sexually and can’t understand the potential consequences of this. His endocrinologist says the medical needs for his testosterone (preventing osteoporosis etc.) far outweigh the negative behavioural effects, but an obstetrician friend has questioned why he’s receiving this treatment if it’s having such a negative impact on the quality of life. What can we do?

We are sorry to hear about the issues that seem to be arising from your son’s testosterone treatment. While we have not seen this specific situation before, it might be that asking for a referral to another consultant, perhaps in another hospital or in a more specialised setting, might be useful. A different view or a greater knowledge of the latest treatments and approaches can sometimes be found in a second opinion, though there is no guarantee that their view will differ from that of your current endocrinologist.
Developing a mature approach to relationships can be challenging, particularly for people with learning differences, and it might be worth speaking to Social Services or other support organisations about this. Local authorities sometimes have their own counsellors working with adults with learning disabilities, or they may be willing to signpost a local organisation providing this type of help. Mencap produce a guide (Sexuality and Relationships Resources) which may contain useful resource links.

My 20-year-old son was diagnosed with Noonan’s when he was 10 years old. With a lot of support and help he did reasonably well at school and college, but is now struggling to adapt to adult life out in the workplace. He finds it particularly difficult to express his feelings and emotions. I just wondered if you could recommend someone who might be able to help or offer advice.

It’s understandable there will be some challenges in moving from the safe and known environment of education into the new and at times confusing world of work. Mencap have produced a resource leaflet which may have some useful links for help with building relationships and expressing emotions. Keyworkers at support organisations are very experienced in working with these sorts of issues, and can offer advice to parents as well as directly support your son.
There are also organisations who support adults with learning difficulties in employment, acting as a bridge between the employee and employer to ensure the employee is fully supported with practical issues around employment (understanding HR and payroll etc.) as well as workplace relationships. If you do an internet search on ‘supported employment services’ in your area, you should find the organisations that help with this. They are also a useful point of contact for other activities and specialists in your area who may be able to provide specific support to you and your son.