medwireNews: Individuals with Noonan syndrome (NS) harbouring pathogenic variations in the PTPN11 gene respond well to treatment with recombinant human growth hormone (rhGH), retrospective study data show.
By contrast, the benefits among patients with variants in other NS-related genes are less clear, report Alexsandra Malaquias (Universidade de Sao Paulo, Brazil) and colleagues in Hormone Research & Paediatrics.
Malaquias and team reviewed data for 42 patients (69% male, 24% pubertal) with NS with (n=35) or without (n=7) a pathogenic variant in the PTPN11 gene. The mean duration of rhGH treatment was 4.6 years among the PTPN11+ patients and 2.4 years among the PTPN11– patients. Pathogenic variants in the latter group occurred in RAF1, KRAS, SOS1 and SHOC2.
Clinical characteristics were similar between the patients with and without PTPN11 variants at the start of treatment. Overall the mean chronological age was 10.5 years, the mean height standard deviation score (SDS) according to normal Centers for Disease Control and Prevention standards (height-CDC SDS) was –3.2 and the mean height SDS for Brazilian Noonan standards (height-NS SDS) was –0.6.
The researchers report that after 1 year of rhGH therapy at a dose of 33–66 µg/kg per day the PTPN11+ patients had a better growth response than PTPN11– patients.
Specifically, growth velocity SDS increased from –1.2 to 3.1 in PTPN11+ patients compared with an increase from –1.9 to –0.1 in PTPN11– patients.
Furthermore, the gain in height-CDC SDS during the first year was significantly higher in PTPN11+ patients than PTPN11– patients (0.6 vs 0.1), as was the gain in height-NS SDS (0.6 vs 0.2).
In total, 17 patients reached adult height after approximately 5 years of therapy, of whom 15 were PTPN11+. The mean adult height-CDC SDS and NS SDS overall were –2.1 and 0.7, respectively, with corresponding total height SDS gains of 1.3 and 1.5.
Males achieved a mean final height of 160.0 cm while that of females was 153.5 cm, and the investigators point out that 41% of participants reached an adult height in the normal range for CDC standards, with almost all of them reaching a Brazilian height-NS SDS above the mean.
Malaquias et al also note that the “improvement in adult height observed in patients with NS is similar to that observed in [small for gestational age] children and girls with Turner syndrome.”
The authors conclude that their results “support rhGH therapy to improve adult height in patients with NS associated with PTPN11 mutation,” but point out that the small number of patients with pathogenic variants in other NS-related genes prevented “an adequate comparison among different NS genotypes.”
Finally, the team cautions that “the decision to treat short children without [growth hormone deficiency] to increase height gain should be carefully debated with parents (or even the child),” particularly as no data on long-term safety are currently available in NS.
In the current study, two of the 30 patients who prematurely discontinued treatment did so due to deterioration of cardiac function, while another two experienced deterioration of scoliosis.
By Laura Cowen
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Horm Res Pediatr 2019; doi:10.1159/000500264