title: Response to long-term growth hormone therapy in patients affected by RASopathies and growth hormone deficiency: Patterns of growth, puberty and final height data.
abstract: RASopathies are developmental disorders caused by heterozygous germline mutations in genes encoding proteins in the RAS-MAPK signaling pathway. Reduced growth is a common feature. Several studies generated data on growth, final height (FH), and height velocity (HV) after growth hormone (GH) treatment in patients with these disorders, particularly in Noonan syndrome, the most common RASopathy. These studies, however, refer to heterogeneous cohorts in terms of molecular information, GH status, age at start and length of therapy, and GH dosage. This work reports growth data in 88 patients affected by RASopathies with molecularly confirmed diagnosis, together with statistics on body proportions, pubertal pattern, and FH in 33, including 16 treated with GH therapy for proven GH deficiency. Thirty-three patients showed GH deficiency after pharmacological tests, and were GH-treated for an average period of 6.8 ± 4.8 years. Before starting therapy, HV was -2.6 ± 1.3 SDS, and mean basal IGF1 levels were -2.0 ± 1.1 SDS. Long-term GH therapy, starting early during childhood, resulted in a positive height response compared with untreated patients (1.3 SDS in terms of height-gain), normalizing FH for Ranke standards but not for general population and Target Height. Pubertal timing negatively affected pubertal growth spurt and FH, with IGF1 standardized score increased from -2.43 to -0.27 SDS. During GH treatment, no significant change in bone age velocity, body proportions, or cardiovascular function was observed.
authors.affiliation: Pediatric Endocrinology and Rare Diseases Unit, Department of Pediatrics, S.Orsola-Malpighi University Hospital-University of Bologna, Bologna, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Tamburrino
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: Dino
authors.initials: D
authors.lastname: Gibertoni
authors.affiliation: Department of Medical Genetics, S.Orsola-Malpighi University Hospital, University of Bologna, Bologna, Italy.
authors.forename: Cesare
authors.initials: C
authors.lastname: Rossi
authors.affiliation: Pediatric Endocrinology and Rare Diseases Unit, Department of Pediatrics, S.Orsola-Malpighi University Hospital-University of Bologna, Bologna, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Scarano
authors.affiliation: Pediatric Endocrinology and Rare Diseases Unit, Department of Pediatrics, S.Orsola-Malpighi University Hospital-University of Bologna, Bologna, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Perri
authors.affiliation: Pediatric Endocrinology and Rare Diseases Unit, Department of Pediatrics, S.Orsola-Malpighi University Hospital-University of Bologna, Bologna, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Montanari
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Fantini
authors.affiliation: Pediatric Endocrinology and Rare Diseases Unit, Department of Pediatrics, S.Orsola-Malpighi University Hospital-University of Bologna, Bologna, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pession
authors.affiliation: Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.|Malattie Genetiche e Malattie Rare, Ospedale Pediatrico Bambino Gesù IRCCS, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Tartaglia
authors.affiliation: Pediatric Endocrinology and Rare Diseases Unit, Department of Pediatrics, S.Orsola-Malpighi University Hospital-University of Bologna, Bologna, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Mazzanti
mesh_terms: D001827:Body Height / Q000187:drug effects*; D002648:Child; D015331:Cohort Studies; D005260:Female; D048788:Growth and Development / Q000187:drug effects*; D019382:Human Growth Hormone / Q000172:deficiency* / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D011627:Puberty / Q000187:drug effects*; D013997:Time Factors; D016896:Treatment Outcome; D018631:ras Proteins / Q000172:deficiency* / Q000378:metabolism
chemical_list: D019382:Human Growth Hormone; D018631:ras Proteins
keywords: RASopathies; final height; growth hormone; noonan syndrome; puberty