AUTHOR=Savarese Emanuela , Di Felice Benedetta , Miconi Francesco , Cabiati Gabriele , Celi Federica , Crescenzi Francesco , Principi Nicola , Esposito Susanna 

TITLE=An Association of PTPN11 and SHOX Mutations in a Male Presenting With Syndromic Growth Failure

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 9 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2018.00557

DOI=10.3389/fendo.2018.00557

ISSN=1664-2392

ABSTRACT=In children with genetic syndromes, short stature is frequently a characteristic feature that, when associated with other specific manifestations, significantly aids in clinical diagnosis. In this report, an atypical case of Noonan syndrome (NS) in a 5.5-year-old child with mesomelic short stature is described. Genetic tests revealed two different mutations in this child. As expected in an NS case, a mutation in PTPN11 gene related to the RAS/MAPK signal transduction pathway was identified. Moreover, a mutation in the SHOX gene that was able to cause disproportionate short stature was detected. This case exemplifies the difficulties that can be encountered in achieving proper diagnoses for children with syndromic diseases and highlights the role of genetic tests in identifying final diagnoses in these patients. Because haploinsufficiency and complete loss of function of SHOX gene are associated with the atypical differentiation and proliferation of chondrocytes, a clinical picture of NS with mesomelic short stature makes the diagnosis even more difficult, which could limit or prevent growth hormone (GH) administration, which has been found to effectively increase linear growth velocity.