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We aimed to assess clinical characteristics and response to growth hormone (GH) therapy in a genetically confirmed, single-country multicentre NSSD cohort. We included 101 patients with NSSD (56 males) from six centres: 76 with (likely) pathogenic\n                      <jats:italic>PTPN11<\/jats:italic>\n                      variants, 7 with\n                      <jats:italic>SOS1<\/jats:italic>\n                      variants, and 18 with other gene variations. All completed at least one year of GH therapy; 23 reached final height. Parental heights were below average (fathers:\u2009\u2212\u20090.33 SDS [\u2212\u20091.19; 0.39],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01; mothers:\u2009\u2212\u20090.68 SDS [\u2212\u20091.47; 0.12],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001; medians [IQR]). SOS1-NS patients were born earlier (gestational week 36 [31; 37]) compared to\n                      <jats:italic>PTPN11<\/jats:italic>\n                      -NS. Birth length (\u2212\u20091.23 SDS [\u2212\u20091.74;\u2009\u2212\u20090.57]) was more reduced than weight (\u2212\u20090.29 SDS [\u2212\u20091.10; 0.54];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001);\n                      <jats:italic>PTPN11-<\/jats:italic>\n                      NS\n                      <jats:italic>\/SOS1<\/jats:italic>\n                      -NS had the lowest birth weights (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). GH was started at 6.4\u00a0years (3.8; 9.5), with baseline height-SDS\u2009\u2212\u20092.92 (\u2212\u20093.64;\u2009\u2212\u20092.47). Median annual height-SDS increments were similar across genotypes: 0.61 (year 1;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009101), 0.28 (year 2;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200992), 0.21 (year 3;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200977), 0.07 (year 4;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200963), and 0.09 (year 5;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200941), leading to height-SDS\u2009\u2212\u20091.97 (\u2212\u20092.81;\u2009\u2212\u20091.42) after 5\u00a0years. Menarche occurred at age 15.7 (13.8; 17.2) years (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200913), and final height-SDS (available in 23 patients) reached\u2009\u2212\u20091.68 (\u2212\u20092.65;\u2009\u2212\u20090.41).\n                    <\/jats:p>\n                    <jats:p>\n                      <jats:italic>Conclusions<\/jats:italic>\n                      Growth restriction in NSSD begins prenatally, especially in PTPN11-NS and SOS1-NS. GH therapy was associated with improved height SDS, with the largest height gains observed before puberty. Earlier treatment initiation may therefore be beneficial for growth outcomes.\n                    <\/jats:p>\n                    <jats:p>\n                      <jats:table-wrap>\n                        <jats:table>\n                          <jats:tbody>\n                            <jats:tr>\n                              <jats:td colspan=\"2\">\n                                <jats:bold>What is Known:<\/jats:bold>\n                                \u2022\n                                <jats:italic>Noonan syndrome spectrum disorders (NSSD) are genetically heterogeneous, with pathogenic variants in the PTPN11 and SOS1 genes being most prevalent. Phenotypic differences among genotypes remain poorly defined.<\/jats:italic>\n                                \u2022\n                                <jats:italic>Short stature is a key NSSD feature. Growth hormone (GH) therapy is beneficial, but prior studies lacked genetic justification or had limited sample sizes.<\/jats:italic>\n                              <\/jats:td>\n                            <\/jats:tr>\n                            <jats:tr>\n                              <jats:td colspan=\"2\">\n                                <jats:bold>What is New:<\/jats:bold>\n                                \u2022\n                                <jats:italic>We analysed perinatal data and real-life GH outcomes in 101 genetically confirmed NSSD cases.<\/jats:italic>\n                                \u2022\n                                <jats:italic>SOS1-NS was linked to prematurity. Birth length was more reduced than weight across genotypes; PTPN11\/SOS1 cases had the lowest birth weights. GH therapy was associated with an increase in height SDS from\u2009\u2212\u20092.92 to\u2009\u2212\u20091.97 (median) following 5\u00a0years, and to\u2009\u2212\u20091.68 in those with final height.<\/jats:italic>\n                              <\/jats:td>\n                            <\/jats:tr>\n                          <\/jats:tbody>\n                        <\/jats:table>\n                      <\/jats:table-wrap>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00431-026-06764-2","type":"journal-article","created":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T01:58:02Z","timestamp":1769219882000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Noonan syndrome spectrum disorders in real life: patient characteristics and response to growth hormone therapy in a genetically defined single-country multicenter 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