Approach

There is no specific treatment for Noonan syndrome. Treatment focuses on the individual symptom, and may include surgery for undescended testes in boys, optimisation of cardiac function, and growth hormone (GH) treatment for short stature.[60]

It is important to note specific medical conditions that are associated with NS. Some patients may not have the constellation of facial characteristics, but may present with associated medical conditions. These include: skeletal abnormalities, including chest deformity; variable degrees of developmental delay; ophthalmic and hearing deficits; coagulation defects; autoimmune disease; and lymphatic dysplasia. Appropriate investigations and specialist consults should be obtained.

Cryptorchidism

Undescended testes are presenting features in most boys (60% to 69%) and may be associated with delayed puberty.[1] The surgical approach is determined by surgeon preference, and is generally through an inguinal or scrotal incision. The optimal timing for surgical therapy is debated, but recent data suggest that there may be better preservation of spermatogenesis and hormonal production, with decreased risk of testicular cancer, when surgery is performed early, ideally prior to 2 years of age, with some suggesting before 1 year of age.[65]

Congenital heart anomalies

These defects may occur in up to 75% of cases and are the most common cause of death for people with the syndrome.[1] They include pulmonary valve stenosis and/or dysplasia, hypertrophic cardiomyopathy, septal defects, and tetralogy of Fallot.[30][55][56][57]

Comprehensive cardiovascular evaluation at the time of diagnosis is imperative. Subsequent treatment will be guided by the specific anomaly identified. Pulmonary valve dysplasia may respond to balloon valvuloplasty, but may require valve replacement.[56] Hypertrophic cardiomyopathy may be treated by beta-blockade or calcium-channel blockade, but occasionally requires surgical myomectomy.[56][57]

Cardiac care should continue into adulthood, as there can be ongoing morbidity and mortality associated with the defects.[30][56] In some centres, children with cardiac anomalies should be transferred to an Adult Congenital Heart Disease clinic at age 18 years, while in other centres, patients will continue to see paediatric cardiologists.

Poor growth

Poor growth, short stature, and an attenuated pubertal growth spurt are common features and may be the presenting symptoms of NS. Children with documented poor growth should be referred to an endocrinologist. Early initiation of GH therapy may facilitate growth optimization, but risks and benefits of comorbidities of NS such as hypertrophic cardiomyopathy and scoliosis must be considered.

Studies of growth hormone (GH) treatment in Noonan syndrome report height gains of 13 cm (5 inches) for males.[66][67][68] The US National Cooperative Growth study demonstrated near-adult height gains of up to 15 cm (6 inches) in patients (mean starting age of 11.6 years) treated for an average of 5 years.[69] The duration of prepubertal treatment was an important contributor to change in height, suggesting greater growth potential with earlier treatment initiation.[69][66] Treatment effect is monitored by the growth response and insulin-like growth factor 1 (IGF-1) levels.

Pathogenic variants in the PTPN11 gene have been associated with reduced growth response to GH in NS.[25][15][70][71] However, other studies report that response to GH therapy does not differ significantly according to genotype.[72][73][74][75] Large prospective studies are required to determine whether genotype influences response to GH therapy.

Use of this content is subject to our disclaimer