Noonan's 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'.
It is now recognised that females are affected by Noonan's 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's 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. Sporadic cases offer no increased risk to the next sibling.
- Offspring of affected individuals have a 50% chance of developing Noonan's syndrome.
- There are few associated fertility problems in females; therefore, the mother is more commonly the transmitting parent.
- The first specific gene for Noonan's syndrome - PTPN11 was discovered in 2001. It is the most common and is found in 50% of cases. Others are KRAS, SOS1, NF1 and RAF1.
The incidence of Noonan's syndrome appears consistent worldwide.
Noonan's syndrome should be considered in all fetuses with polyhydramnios, pleural effusions, oedema and increased nuchal fluid with a normal karyotype.
The disorder is present from birth, but age impacts on facial phenotype. Infants can be quite difficult to recognise, but appearance becomes more striking in early childhood.
- 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.
- The arms may be held at an unusual angle - cubitus valgus.
- Short stature is present in up to 80%. Average male height is 5 feet 5 inches. Females average to 5 feet.
- Low-set or abnormally shaped ears, ptosis, anti-mongoloid palpebral slant and wide spacing of the eyes - hypertelorism.
- Triangular-shaped face.
- There may be signs of congenital heart disease in 50%.
- 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, eg XI-XIII.
- Undescended testicles, delayed puberty, small penis.
- There are learning difficulties in 25% of patients.
- 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%).
- Fetal alcohol syndrome.
- Fetal hydantoin syndrome.
- Multiple lentigines syndrome.
- Cardio-facial-cutaneous syndrome.
- XO/XY mosaicism.
- Turner's syndrome.
- Jacobsen's syndrome.
- Genetic testing is important for karyotype analysis, to ensure no easily detectable chromosome abnormality is mistaken for Noonan's 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%.
- Assessment of development to identify delays and allow for intervention. IQ ranges from 48-130 with a mean of 86.1.
There is no single treatment available for Noonan's syndrome. Treatment is problem-focused.
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 are 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 learning difficulties are present, they are usually mild.
A DNA test for mutation analysis can be carried out on blood, chorionic villi and amniotic fluid samples.
Further reading & references
- Ibrahim J et al, Noonan Syndrome, Medscape, April 2010
- Cesur Aydin K, Ozcan I; Noonan syndrome. A review. Minerva Pediatr. 2008 Jun;60(3):343-6.
- Sharland M, Morgan M, Smith G, et al; Genetic counselling in Noonan syndrome. Am J Med Genet. 1993 Feb 15;45(4):437-40.
- Tartaglia M, Mehler EL, Goldberg R, et al; Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. Nat Genet. 2001 Dec;29(4):465-8.
- Padidela R, Camacho-Hubner C, Attie KM, et al; Abnormal growth in noonan syndrome: genetic and endocrine features and optimal treatment. Horm Res. 2008;70(3):129-36. Epub 2008 Jul 29.
- Noonan Syndrome, Online Mendelian Inheritance in Man (OMIM)
- Marino B, Digilio MC, Toscano A, et al; Congenital heart diseases in children with Noonan syndrome: An expanded cardiac spectrum with high prevalence of atrioventricular canal. J Pediatr. 1999 Dec;135(6):703-6.
- Singer ST, Hurst D, Addiego JE Jr; Bleeding disorders in Noonan syndrome: three case reports and review of the literature. J Pediatr Hematol Oncol. 1997 Mar-Apr;19(2):130-4.
- Mattina T, Perrotta CS, Grossfeld P; Jacobsen syndrome. Orphanet J Rare Dis. 2009 Mar 7;4:9.
- Qiu WW, Yin SS, Stucker FJ; Audiologic manifestations of Noonan syndrome. Otolaryngol Head Neck Surg. 1998 Mar;118(3 Pt 1):319-23.
- van der Burgt I, Thoonen G, Roosenboom N, et al; Patterns of cognitive functioning in school-aged children with Noonan syndrome associated with variability in phenotypic expression. J Pediatr. 1999 Dec;135(6):707-13.
- Romano AA, Dana K, Bakker B, et al; Growth response, near-adult height, and patterns of growth and puberty in J Clin Endocrinol Metab. 2009 Jul;94(7):2338-44. Epub 2009 Apr 28.
- van der Burgt I; Noonan syndrome. Orphanet J Rare Dis. 2007 Jan 14;2:4.
|Original Author: Dr Hayley Willacy||Current Version: Dr Hayley Willacy|
|Last Checked: 20/04/2011||Document ID: 2518 Version: 22||© EMIS|
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