Response to long-term growth hormone therapy in patients affected by RASopathies and growth hormone deficiency

Patterns of growth, puberty and final height data

Federica Tamburrino, Dino Gibertoni, Cesare Rossi, Emanuela Scarano, Annamaria Perri, Francesca Montanari, Maria Pia Fantini, Andrea Pession, Marco Tartaglia, Laura Mazzanti

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2786-2794
Number of pages9
JournalAmerican Journal of Medical Genetics, Part A
Volume167
Issue number11
DOIs
Publication statusPublished - Nov 1 2015

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Puberty
Growth Hormone
Growth
Therapeutics
Noonan Syndrome
Germ-Line Mutation
Health Services Needs and Demand
Pharmacology
Bone and Bones

Keywords

  • Final height
  • Growth hormone
  • Noonan syndrome
  • Puberty
  • RASopathies

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Response to long-term growth hormone therapy in patients affected by RASopathies and growth hormone deficiency : Patterns of growth, puberty and final height data. / Tamburrino, Federica; Gibertoni, Dino; Rossi, Cesare; Scarano, Emanuela; Perri, Annamaria; Montanari, Francesca; Fantini, Maria Pia; Pession, Andrea; Tartaglia, Marco; Mazzanti, Laura.

In: American Journal of Medical Genetics, Part A, Vol. 167, No. 11, 01.11.2015, p. 2786-2794.

Research output: Contribution to journalArticle

Tamburrino, Federica ; Gibertoni, Dino ; Rossi, Cesare ; Scarano, Emanuela ; Perri, Annamaria ; Montanari, Francesca ; Fantini, Maria Pia ; Pession, Andrea ; Tartaglia, Marco ; Mazzanti, Laura. / Response to long-term growth hormone therapy in patients affected by RASopathies and growth hormone deficiency : Patterns of growth, puberty and final height data. In: American Journal of Medical Genetics, Part A. 2015 ; Vol. 167, No. 11. pp. 2786-2794.
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