Noonan syndrome is a genetic disorder characterized by short stature, congenital heart disease, and developmental delays. Other features of the disease include a wide and winged neck, pigeon chest, funnel chest, and other thoracic deformities. Stationary testes, specific facial features, coagulation abnormalities, lymphatic abnormalities, and abnormalities in the formation of eyes and ears are also observed. Described in 1963 by therapist Jacqueline Noonan, the syndrome has an incidence of close to 1/2000 births. It is a syndrome of genetic origin that occurs sporadically in more than 80% of cases or according to an autosomal dominant transmission with variable expression. (1)
The birth height of the patients is usually normal, but adult height is lower than normal. Congenital heart disease is found in 50-80% of patients. Pulmonary stenosis with dysplasia is the most common appearance. Cardiac symptoms are found in 20-50% of patients, while hypertrophic cardiomyopathy is found in 20-30% of patients and is identified after birth or in infancy. (2)
Other cardiovascular abnormalities include ventricular septal defect, tetralogy of Fallot, pulmonary artery branching stenosis, and atrial septal defect. About one-third of the patients have mild mental retardation.
Can You Die From The Noonan Syndrome?
Patients with Noonan syndrome usually have a normal lifespan. However, several factors may shorten the life expectancy of the patient compared to a normal individual. The most common cause of the hampered prognosis of Noonan syndrome patients is cardiovascular disorders. Some patients may also develop carcinomas in the blood including leukemia. So careful and regular monitoring of the patient is necessary once the diagnosis confirms Noonan syndrome. Prompt symptomatic therapy addressing the issues often make the patients live a standard life with normal life expectancy. (1)
Epidemiology Of Noonan Syndrome
Noonan syndrome incidence is 1 in 1000 to 2500 births, and there are many sporadic cases, but autosomal dominant inheritance cases have also been reported. In family history, it is often transmitted through affected women, presumably because the fertility of affected men is reduced due to retention testis or Hypogenitalia hypoplasia. (1)
Noonan syndrome is diagnosed with major clinical symptoms. The most common criterion for clinical diagnosis involves pediatric endocrinology. Newborns with Noonan syndrome usually have a size, weight, and head circumference within normal limits. Diagnosis at birth is based on a combination of facial dysmorphism, a short neck with excess skin, cardiac abnormalities and, more rarely, lymphatic issues. There are often problems with blood circulation and excess bleeding. However, these symptoms are inconsistent and may be inconspicuous, as evidenced by an average age at diagnosis of 9 years. The facial dysmorphism of Noonan syndrome is quite characteristic, nevertheless, the facial features are variable in time and the dysmorphism evolves with age, making diagnosis difficult.
Chromosomal examination of the patient is routine. Examination of the four genes responsible for Noonan syndrome is done to check for mutations – PTPN11 (in 50% of patients), KRAS (less than 5% patients), SOS1 (about 13% of patients), and RAF1 (3-17% of patients). (3)
Clinical Management Of Noonan Syndrome
Treatment of cardiovascular abnormalities in Noonan syndrome is the same as usual. Developmental disorders are addressed by early education programs, personalized education, and personality management. Excess bleeding treatment is done by addressing specific coagulation factor deficiencies or platelet aggregation abnormality. The growth rate is increased by growth hormone replacement therapy. Regular follow-up measures are taken for quick identification of organ deformities (particularly cardiovascular abnormality). There are no major problems with the patient’s prognosis. (3) (4)
Genetic Counseling For Syndrome
Noonan syndrome exhibits an autosomal inheritance, with most affected individuals being subject to nascent mutations. About 30-75% of patients have inherited the disease from the parents (mostly from mothers). The risk of disease transmission to offspring depends on the genetic status of the parents. If either parent is affected, the risk is 50%, while the risk of children getting the disease is low (<1%) when parents are clean. Prenatal diagnosis is possible if a genetic mutation has been identified in any family member. (5)
- Kruszka P, Porras AR, Addissie YA, et al. Noonan syndrome in diverse populations. American Journal of Medical Genetics Part A. 2017;173(9):2323-2334.
- Noonan JA. Noonan syndrome. Health Care for People with Intellectual and Developmental Disabilities across the Lifespan: Springer; 2016:827-832.
- Romano AA, Allanson JE, Dahlgren J, et al. Noonan syndrome: clinical features, diagnosis, and management guidelines. Pediatrics. 2010;126(4):746-759.
- Osio D, Dahlgren J, Wikland KA, Westphal O. Improved final height with long‐term growth hormone treatment in Noonan syndrome. Acta Paediatrica. 2005;94(9):1232-1237.
- Roberts AE, Allanson JE, Tartaglia M, Gelb BD. Noonan syndrome. The Lancet. 2013;381(9863):333-342.
- Can You Detect Noonan Syndrome Before Birth & Is It More Common In Males Or Females?
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- What Is The Prognosis For Noonan Syndrome?
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