Management strategies for optimal linear growth in Noonan syndrome (NS) children: minireview and case series of three patients with NS due to PTPN11 mutation and confirmed growth hormone deficiency
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Abstract
Noonan syndrome (NS) is a disease in which molecular genetic tests reveal mutations in the genes responsible for the RAS/MAPK signalling pathway, most often PTPN11. Short stature leading to unsatisfactory final height (FH) is one of the components of NS. It is an established worldwide practice to treat NS children with recombinant human growth hormone (rhGH), but in Poland it remains a controversial issue and typically is only recommended in cases of concomitant growth hormone deficiency (GHD), in which the therapy is considered as substitutive. In this paper, therefore, we present the most recent available knowledge on the principles of rhGH treatment in children with NS, as well as an analysis of the course of treatment in 3 of our own cases, which were challenging for the clinicians treating them.
rhGH therapy improves linear growth and FH in NS patients; however, not all children achieve satisfactory results. The aim of the article is to summarise the results of long-term rhGH treatment used as monotherapy or — in cases of deteriorating growth prognosis during monotherapy — combined with pharmacological inhibition of puberty [with gonadotropin-releasing hormone analogues (GnRHa)]
or of epiphyseal ossification [with aromatase inhibitors (AI)] in 3 NS children due to PTPN11 mutation. Height standard deviation score (hSDS) during treatment improved in all children by 1.6 ± 0.67. We observed a positive correlation between height velocity (HV) and the insulin-like growth factor 1/insulin-like growth factor binding protein 3 (IGF-1/IGFBP-3) molar ratio SDS (r = 0.41). We discuss
our results with data from the literature, presenting a mini review.
Conclusions:
1. IGF-1/IGFBP-3 molar ratio SDS assessment helps to optimise the rhGH doses in NS children.
2. Although rhGH therapy generally improves HV and FH in short NS children, if the growth prognosis during therapy worsens, it is worth considering additional treatment with GnRHa or AI.
Keywords: growthgrowth hormone deficiencygrowth hormone therapyshort statureNoonan syndromePTPN11molecular diagnosticsIGF-1IGFBP-3letrozoleGnRH agonist
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