medwireNews: Italian clinicians have published a set of consensus statements on the multidisciplinary diagnosis, care and treatment of patients with Noonan syndrome (NS) from childhood and beyond.
“This initiative was driven by the need for updated and comprehensive recommendations for the NS treatment”, say Mohamad Maghnie (Istituto Giannina Gaslini, Genoa) and co-authors in JAMA Network Open.
“These recommendations must be interpreted and adapted by clinicians following their local clinical infrastructure, resource availability, and patient population to ensure feasible implementation.”
The authors report that a steering committee, consisting of three paediatric endocrinologists, a paediatric cardiologist and a molecular geneticist, used a modified Delphi process to draft 47 statements based on evidence and clinical experience.
These statements were then voted on by a panel of 25 expert clinicians who care for patients with NS in Italy, with 100% agreement achieved on the need for:
- prompt molecular characterisation of NS to confirm diagnosis and guide prognosis and treatment;
- a multidisciplinary approach to caring for patients with NS;
- improved care for patients transitioning between paediatric and adult services;
- acknowledgement of the increased risk profile of patients with NS-related hypertrophic cardiomyopathy (HCM) and their reduced life expectancy;
- monitoring of adherence to growth hormone (GH) therapy;
- partial GH insensitivity not being considered a barrier to GH therapy; and
- recognition of safety concerns with GH therapy, especially those relating to HCM and malignancy.
The authors say that expert comments during the process highlighted that “patient genotyping faces obstacles in many centers”, including access to advanced diagnostic tools, cost and poor awareness of NS facial features during foetal ultrasound.
They note that foetal ultrasounds indicating HCM or supravalvular pulmonary valve stenosis with valve dysplasia may flag the need for genetic testing for NS, while known genotype–phenotype associations can guide clinical care, such as the relationship between variations in RAF1, RIT1 and LZTR1 and an increased risk of HCM.
Maghnie and team emphasise that “[e]arly diagnosis and multidisciplinary treatment are essential to improve health outcomes and enhance long-term development and [quality of life].” In particular, they highlight that coordinated and comprehensive care involving specialists, such as endocrinologists, cardiologists, neurologists and rehabilitation specialists, is linked to earlier achievement of “key milestones” and fewer hospital stays.
The authors also observe that the majority of children with NS have short stature and delayed pubertal growth, resulting in an adult height of around –2 SDS. While Italian guidelines state that GH therapy is reimbursable for patients with a genetically confirmed NS diagnosis and a height of –2.5 SDS or less, Maghnie et al note that current guidelines restrict use for children with a height between –2.0 and –2.5 SDS, whereas some other countries have “less stringent” or no specified height criteria for GH use in children with NS-related growth failure or short stature.
The consensus statements state that patients should undergo magnetic resonance imaging of the hypothalamus and pituitary to assess for malignancy before beginning GH therapy, be assessed for glucose, lipid, coagulation and thyroid markers during treatment, and be monitored regularly for insulin-like growth factor-1 and growth velocity to determine treatment efficacy.
“If [GH] is unavailable, alternatives such as nutritional optimization, gonadotropin-releasing hormone analogs, aromatase inhibitors, and other investigational options should be individualized and used cautiously due to potential adverse effects”, the team advises.
By Lynda Williams
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