Growth in Children With Noonan Syndrome and Effects of Growth Hormone Treatment on Adult Height.
Annachiara Libraro, Vito D'Ascanio, Marco Cappa, Mariangela Chiarito, Maria Cristina Digilio, Silvia Einaudi, Anna Grandone, Mohamad Maghnie, Laura Mazzanti, Alessandro Mussa, Giuseppa Patti, Emanuela Scarano, Antonietta Spinuzza, Silvia Vannelli, Malgorzata Gabriela Wasniewska, Giovanni Battista Ferrero, Maria Felicia Faienza
Author Information
Annachiara Libraro: Department of Biomedical Sciences and Human Oncology, Pediatric Unit, University of Bari "A. Moro", Bari, Italy.
Vito D'Ascanio: National Research Council-Institute of Sciences of Food Production (CNR-ISPA), Bari, Italy.
Marco Cappa: Unit of Endocrinology, Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy.
Mariangela Chiarito: Department of Biomedical Sciences and Human Oncology, Pediatric Unit, University of Bari "A. Moro", Bari, Italy.
Maria Cristina Digilio: Genetics and Rare Diseases Research Division, Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy.
Silvia Einaudi: Department of Pediatric Endocrinology and Diabetology, Regina Margherita Children Hospital, University of Turin, Turin, Italy.
Anna Grandone: Department of Woman, Child and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples, Italy.
Mohamad Maghnie: Department of Pediatrics, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Giannina Gaslini, Genova, Italy.
Laura Mazzanti: Pediatric Rare Diseases Unit, Department of Pediatrics, St. Orsola University Hospital, University of Bologna, Bologna, Italy.
Alessandro Mussa: Department of Public Health and Pediatrics, University of Torino, Torino, Italy.
Giuseppa Patti: Department of Pediatrics, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Giannina Gaslini, Genova, Italy.
Emanuela Scarano: Pediatric Rare Diseases Unit, Department of Pediatrics, St. Orsola University Hospital, University of Bologna, Bologna, Italy.
Antonietta Spinuzza: Department of Human Pathology of Adulthood and Childhood Gaetano Barresi, Gaetano Martino University Hospital, University of Messina, Messina, Italy.
Silvia Vannelli: Department of Pediatric Endocrinology and Diabetology, Regina Margherita Children Hospital, University of Turin, Turin, Italy.
Malgorzata Gabriela Wasniewska: Department of Human Pathology of Adulthood and Childhood Gaetano Barresi, Gaetano Martino University Hospital, University of Messina, Messina, Italy.
Giovanni Battista Ferrero: Department of Clinical and Biological Sciences, University of Torino, Torino, Italy.
Maria Felicia Faienza: Department of Biomedical Sciences and Human Oncology, Pediatric Unit, University of Bari "A. Moro", Bari, Italy.
Objectives: Growth impairment is a common manifestation in Noonan syndrome (NS). Recombinant humanGH (rhGH) treatment has been shown to increase growth and adult height (AH) in a few studies. We aimed to evaluate the growth trajectory towards the AH, and the effects of rhGH treatment in a large cohort of NS children. Methods: Retrospective, multicenter, cohort study including subjects with genetic diagnosis of NS. A total of 228 NSpatients, 154 with mutations, 94 who reached AH, were recruited. Auxological data were collected at 2, 5, and 10 years, at pubertal onset, at AH. Sixty-eight NS subjects affected with GH deficiency (GHD) were treated with rhGH at a mean dose of 0.24 mg/kg per week until AH achievement. Results: ANOVA analysis showed a significant difference between birth length and height standard deviation scores (HSDS) at the different key ages (), while no significant differences were found between HSDS measurements at 2, 5, and 10 years, at pubertal onset, and at AH. HSDS increased from -3.10 ± 0.84 to -2.31 ± 0.99 during rhGH treatment, with a total height gain of 0.79 ± 0.74, and no significant difference between untreated and treated NS at AH. Conclusions: rhGH treatment at the standard dose used for children with GH idiopathic deficiency is effective in improving growth and AH in NS with GHD. Further studies are needed to assess genotype-specific response to rhGH treatment in the different pathogenic variants of gene and in the less common genotypes.
