Noonan syndrome and other RASopathies: Aetiology, diagnostic procedures and therapy
Authors:
J. Lebl; S. Koloušková; L. Toni; A. Kodýtková; S. A. Amaratunga; L. Plachý; Š. Průhová
Authors‘ workplace:
Pediatrická klinika 2. lékařské fakulty UK a Fakultní nemocnice Motol, Praha
Published in:
Čes-slov Pediat 2020; 75 (4): 219-226.
Category:
Overview
Noonan syndrome and related conditions are classified as RASopathies due to their shared molecular pathogenesis. They represent frequent developmental syndromes with prevalence ranging from 1:1000 to 1:2500 live-born children, and follow an autosomal dominant mode of inheritance, with up to 60% of cases occurring sporadically due to de novo gene mutations. RASopathies are clinically characterized by the typical facial phenotype, delayed growth, and cardiac disease – predominantly pulmonary stenosis (50–60%) and/or hypertrophic cardiomyopathy (20%). Typical clinical presentations include failure to thrive with developmental delay and macrocephaly in infants, and growth delay with typical facial appearance and heart disease in older children. Adults with Noonan syndrome reach a mean height of only 162.5 cm (males) or 152.7 cm (females), due to the multifactorial growth disorder. Growth hormone administration leads to a final height increase from -2.5 SD to -1.4 SD (mean) and thereby extenuates the height handicap. Since 2020, growth hormone has been approved for treatment in Noonan syndrome in the E.U. by national medicine agencies. Individual treatment decisions are the responsibility of paediatric endocrinologists.
Keywords:
RASopathies – Noonan syndrome – hypertrophic cardiomyopathy – Growth hormone – pulmonary stenosis – growth
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Neonatology Paediatrics General practitioner for children and adolescentsArticle was published in
Czech-Slovak Pediatrics
2020 Issue 4
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