Endocrine Aspects of Noonan Syndrome and Related Syndromes

RASopathies represent a group of diseases that are increasingly being recognized and studied. Consequently, efforts have been made to improve the quality of life of these patients, in particular the treatment with GH because of their short stature. Most papers dealing with the GH treatment of RASopathies concern the Noonan syndrome and the influence of PTPN11 mutations. However, little is known regarding GH treatment and final height in other RASopathies, such as Noonan-like syndrome with loose anagen hair (NS-LAH).

Additionally, nothing is known about the potential cancerogenic risk of GH treatment and whether GH treatment might negatively influence hypertrophic cardiomyopathy (HCM), often seen in these patients.

Another interesting point is the pubertal delay frequently observed of these children. It has not been investigated whether they would benefit from a substitutive treatment and whether this treatment would influence the effect of GH treatment on final height.

This Research Topic is particularly interested in the following areas.
• A review on the physiopathology of growth retardation in RASopathies, with particular interest in some fields that are not yet well defined such as relative GH insensitivity, GH secretion dysfunction, and frequently encountered endochondral ossification abnormalities
• The effect of GH treatment on the final height in RASopathies other than in PTPN11 mutations
• Review on cancer risks in RASopathies and on the possibility of increasing such risks by GH treatment (including recommendations for surveillance)
• Review on hypertrophic cardiomyopathy in RASopathies and the possibility of increased risk of deterioration of HCM by GH treatment (including recommendations for surveillance)
• New therapeutic perspectives (RAS/MAPK modulators)
• Treatment of pubertal delay. Particularly the choice of the treatment with which modalities, and the effects on the final height
• A retrospective study on the fertility in Noonan syndrome
• Clinical and basic science data on metabolic dysfunction
• A review on bone structure, mineralization, strength, and bone metabolism in RASopathies