Noonan's Syndrome

Noonan syndrome is a genetic disorder that causes abnormal development of multiple parts of the body. There is webbing of the neck and different typical chest shapes, giving rise to its alternative name ' Turner-like syndrome of males'. However it is now recognised that females are affected by Noonan syndrome in equal proportion to males.

It is inherited in an autosomal dominant manner. It affects at least 1 in 2,500 children. Some children do not have a parent with Noonan syndrome, reflecting the sporadic inheritance, presumably the result of a new mutation. Once the pattern of inheritance is identified, parents need counselling about recurrence risk with each pregnancy.¹ Sporadic cases offer no increased risk to the next sibling. Offspring of affected individuals have 50% chance of developing Noonan syndrome. There are few associated fertility problems in females, therefore the mother is more commonly the transmitting parent.
The first specific gene for Noonan syndrome - PTPN11 was discovered in 2001.² It is expected that other causative genes will be found.
The incidence of Noonan syndrome appears consistent worldwide.

The disorder is obviously present from birth, but age impacts on facial phenotype. Infants can be quite difficult to recognise, but appearance becomes more striking in early childhood.
Frequently seen abnormalities include ³:

• Webbing and short appearance of the neck.
• Changes in the sternum, usually a sunken chest- pectus excavatum but occasionally pectus carinatum.
• Scoliosis and joint laxity.
• Facial abnormalities include low-set or abnormally shaped ears, ptosis, anti-mongoloid palpebral slant and wide-spacing of the eyes- hypertelorism. Triangular shaped face.
• The arms may be held at an unusual angle- cubitus valgus.
• There may be signs of congenital heart disease in 50%.⁴ The classic lesion is a dysplastic or stenotic pulmonary valve, occurring more commonly than atrial septal defect.
• Hypertrophic cardiomyopathy, obstructive or not, is present in up to 30%.
• Hepatosplenomegaly (unrelated to cardiac status) is present in 25%.
• There may be a coagulation defect in up to 50% of patients, with low platelet count or abnormal levels of coagulation factors e.g. XI- XIII.⁵
• Undescended testicles. Delayed puberty. Small penis.
• Mental retardation in 25% of patients.
• Short stature is present in up to 80%. Average male height is 5ft 5inches. Females average to 5ft.
• Eye and skin findings are present to varying degrees. Strabismus (48%), amblyopia (33%), refractive errors (61%). Prominent finger pads/toe pads. Follicular keratosis. Multiple lentigines.
• Hypotonia. Seizure disorder (13%).

These abnormalities are all reminiscent of Turners syndrome.

• Fetal alcohol syndrome
• Fetal hydantoin syndrome
• Multiple lentigines syndrome
• Cardio-facial-cutaneous syndrome
• XO/XY mosaicism
• Turner syndrome

• Genetic testing is important for karyotype analysis, to ensure no easily detectable chromosome abnormality is mistaken for Noonan syndrome.
• It also potentially provides research genetic testing for mutations in the PTPN11 gene.
• ECG, CXR and echocardiography may be necessary if there are symptoms of congenital heart disease or cardiomyopathy.
• Hearing testing may be necessary, as incidence of high frequency sensorineural hearing loss may be as high as 50%.⁶
• Assessment of development to identify delays and allow for intervention. IQ ranges from 48-130 with a mean of 86.1.⁷

There is no single treatment available for Noonan syndrome. Treatment is problem focused.

Drugs

Growth hormone has been successfully used in the treatment of short stature associated with Noonan syndrome.

Surgical

Certain types of congenital heart lesions are amenable to surgery. Clotting needs to be checked thoroughly prior to surgery.

• Low self esteem.
• Social difficulties related to physical abnormalities.
• Male infertility if both testes undescended.
• Abnormal heart structure.
• Fluid accumulation in tissues- lymphoedema, cystic hygroma.

The outcome is assessed on the extent and severity of the problems in the individual patient.
Patients are able to lead normal lives.
If mental retardation is present, it is usually mild.

There is no accurate prenatal testing available.