An introduction for families, friends and professionals, produced in association with The Noonan Syndrome Support Group Inc.
WHAT IS NOONAN SYNDROME?
The term Noonan Syndrome began to be used in 1963 when Dr. Jacqueline Noonan, a paediatric cardiologist, reported nine children with pulmonary stenosis, short stature, and a characteristic facial appearance.
Noonan Syndrome is a genetic disorder, and is thought to occur in around 1:1500 people. But as there is no definitive test for NS as yet, diagnosis is made on the basis of certain "features". However since these can be very variable, many of the milder cases may never actually be diagnosed.
Facial Features
 | Hypertelorism (widely spaced eyes) |
| Ptosis (droopy eyelids) |
| Downward slanting eyes |
| Flattened nasal bridge |
| Epicanthal folds (excess skin in the inner corner of the eye) |
| Malar hypoplasia (flattened cheek bones) |
| Low set, anteriorly rotated ears |
These features are very variable however, and the degree to which they are expressed can vary widely not only from child to child, but also with age. This can add greatly to the difficulties of diagnosis.
Heart Defects | Pulmonary valve stenosis (PS) |
| Hypertrophic cardiomyopathy (HCM) |
| Atrial septal defect (ASD) |
| Ventral septal defect (VSD) |
Around 80% of babies born with NS have some sort of heart defect, although many are asymptomatic and the defect is only discovered when a ‘heart murmur is heard.
The most common heart defect in NS is a narrowed pulmonary valve (Pulmonary Stenosis), which may also be dysplastic (mis-shaped). Often the narrowing is not severe and in around 90% of cases surgery is not required. Hypertrophic cardiomyopathy is also fairly common, causing a thickening of the heart muscle, often with impaired heart function. However most people with NS who have HCM remain asymptomatic for many years, and in some cases the HCM will actually improve with time. An Atrial Septal Defect is an abnormal opening between the two upper chambers of the heart, resulting in some improper blood flow from the left to the right side of the heart. Whilst small ASD’s may close by themselves, surgical closure of larger defects is often required. Other Features | Short stature |
| Feeding problems |
| Pectus excavatum or carinatum (indentation or protrusion of the breastbone) |
| Broad chest, widely spaced nipples |
| Learning difficulties |
| Undescended testes |
| Webbed neck |
| Low posterior hairline: hair may be sparse, but is often coarse and curly. |
| Bruising and bleeding |
| Muscular and skeletal anomalies |
Growth Hormone (GH) therapy has been used to treat some children and adolescents with Noonan Syndrome; but most children with NS are not actually GH deficient, and although treatment with synthetic GH increases the rate of growth in early childhood, it is not know if the therapy actually increases adult height.
Feeding Problems are very common, particularly in infancy. Babies often have a weak sucking reflex and tend to tire easily during feeding. Some may show little or no interest in feeding at all, and tube feeding may be necessary. Frequent and forceful vomiting is also very common, and difficulties may persist well into the second year. There may also be problems with weaning, but in general the feeding problems tend to improve with time. Learning Difficulties and Mental Retardation. Whilst the majority of individuals with Noonan Syndrome have IQs that fall within the ‘normal’ range, approximately a third will have learning disabilities and around 10% will require significant special education. But severe ‘mental retardation’ is actually quite uncommon.The most common learning difficulty seen in children with Noonan Syndrome is difficulty in verbal reasoning, although the majority will attend normal schools. No specific behavioural pattern has been identified, although individuals with NS often show signs of clumsiness, stubbornness, and irritability.
Physical Development. Infants and children with Noonan Syndrome may present with developmental delays, and developmental milestones tend to be reached at a later than average age. For example, the average age at which an infant with NS can sit alone is 10 months, walk at 21 months, and talk at 31 months. Around 60% of boys with NS will have undescended testes, although early surgical treatment can help prevent problems with fertility. Puberty may be delayed in both boys and girls, on average reaching puberty around 2 years later than their peers. But although the delay in going into puberty may cause emotional concerns for the children involved, it also means that the bones are later in reaching their adult state and so growth may continue for longer.Females with Noonan Syndrome generally have normal menstrual cycles and fertility, but in males some decreased fertility has been observed.
Bruising and Bleeding. Despite the fact that around 65% of children with NS bruise easily, only around 20% have an actual bleeding disorder. The most common of these disorders found in NS are Factor XI deficiency, von Willebrand disease and thrombocytopenia.It has been suggested that individuals with Noonan Syndrome be evaluated for bleeding disorders prior to surgery, and if a bleeding disorder is detected precautions should be taken.
Hearing and Speech. Mild hearing loss occurs in up to 40% of individuals; this is most often the result of recurrent ear infections or glue ear. However around 3% will experience more serious hearing loss and require the use of hearing aids. Any hearing impairment may also result in speech delay. The Eye/Vision. Nearly all individuals with Noonan Syndrome have some associated eye abnormalities, the most common of which are: | hypertelorism (widely spaced eyes) |
| ptosis (droopy eyelids) |
| strabismus (cross eyes) |
| epicanthal folds (folded skin in inner corner of eye) |
| down-slanting eyes |
| amblyopia (reduced vision) |
Many of these contribute to the characteristic facial appearance seen in Noonan Syndrome and do not usually cause vision problems. However up to 50% of individuals with NS will require prescription glasses. Although ptosis and strabismus are not usually severe, in some cases Surgery may be required.
The Lymphatic System. Many individuals with Noonan's have excess skin around the neck. This appears as a webbed neck, which may have been caused by a cystic hygroma (a fluid filled area at the back of the neck) developing during pregnancy. This may be detected by ultrasound examination during pregnancy, although the presence of a cystic hygroma does not give a firm diagnosis of Noonan Syndrome.Lymphoedema, or swelling of the hands and feet, due to an accumulation of lymphatic fluid, is common in new-borns with NS. The swelling usually diminishes with age.
Other problems widely mentioned within parent groups but not generally mentioned in the literature include: | Frequent night-time leg cramps |
| Persistent problems with constipation |
| Difficulty in getting young children to take enough fluids |
| Night sweats |
The causes of these problems are not known and indeed in fact many professionals do not even recognise that they exist. But at NS conferences in the US and the UK, over 200 families were consulted and of these nearly all suffered from one or more of the above problems. And whilst they may not be medically important, they can be very serious problems to the families concerned.
It is recognised that more than one gene may cause Noonan Syndrome, but a gene for NS has been mapped in some families on the long arm of chromosome 12. The gene for NS is dominant, since an abnormality in either one of the pair of genes will give rise to the disorder.
An affected individual has one normal and one altered gene, and therefore has a 50% chance of passing Noonan Syndrome on to each of their children. But as a result of variable expression, children with NS may have either more or less severe characteristics than their parents.
FINDING OUT MORE The Noonan Syndrome Support GroupThe Noonan Syndrome Support Group is an international organisation offering support, information and friendship. Based in the United States, TNSSG has members from all over the world, including Europe, Australasia, South Africa, and the rest of the Americas. You can contact them at:
The Noonan Syndrome Support Group Inc. PO Box 145, Upperco, MD 21155, USA Tel: 001 410-374-5245
If you have Internet access, they have a very good website with a lot of online information, introductions, photographs, links to other sites, and more. The address is http://www.noonansyndrome.org listserv@home.ease.lsoft.com, with only the following in the message body: subscribe noonan-syndrome The Birth Defects Foundation
The Birth Defects Foundation is a national registered charity dedicated to improving child health. Noonan Syndrome has long been a BDF priority for support and funding. The BDF Noonan Syndrome Helpline provides confidential and professional information and support for affected families. You can call them on:
08700 70 70 20They also have a website at http://www.birthdefects.co.uk
Noonan Syndrome Book
A 150 page book on Noonan Syndrome has recently been published:
Noonan Syndrome
Characteristics, Development, and Intervention
by Professor Stephen von Tetzchner,
Institute of Psychology, University of Oslo
The book contains a great deal of useful information, and includes chapters on
| Noonan syndrome - history and definition |
| Medical and physical characteristics |
| Diagnosis, pregnancy, and early development |
| Motor, cognitive, and language development |
| Social development, behavioural disorders, and personality |
| Intervention |
| Research Tasks |
An English edition is available for £10 (plus p&p) from:
Tel: 01606 558337
email: h.nye@bigfoot.com
http://website.lineone.net/~h.nye/index.htm