Effectiveness of growth hormone therapy in children with Noonan syndrome

Seok, Eun Mi; Park, Hong Kyu; Rho, Jung Gi; Kum, Change Dae; Lee, Hae Sang; Hwang, Jin Soon

doi:10.6065/apem.1938154.077

Cited by 7 publications

(7 citation statements)

References 26 publications

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“…Similar results have been reported by Tamburrino et al in a cohort of patients affected by RASopathies (25). Furthermore, Seok et al demonstrated an increase of HSDS and GV after 3 years of treatment in prepubertal NS children, with a similar response between NS and GHD patients (32). Malaquias et al in a cohort of NS PTPN11 + patients demonstrated the benefits of rhGh therapy on AH, compared with a small cohort of PTPN11− subjects (33).…”

Section: Discussionsupporting

confidence: 79%

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Growth in Children With Noonan Syndrome and Effects of Growth Hormone Treatment on Adult Height

et al. 2021

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ObjectivesGrowth impairment is a common manifestation in Noonan syndrome (NS). Recombinant human GH (rhGH) treatment has been shown to increase growth and adult height (AH) in a few studies. We aimed to evaluate the growth trajectory towards the AH, and the effects of rhGH treatment in a large cohort of NS children.MethodsRetrospective, multicenter, cohort study including subjects with genetic diagnosis of NS. A total of 228 NS patients, 154 with PTPN11 mutations, 94 who reached AH, were recruited. Auxological data were collected at 2, 5, and 10 years, at pubertal onset, at AH. Sixty-eight NS subjects affected with GH deficiency (GHD) were treated with rhGH at a mean dose of 0.24 mg/kg per week until AH achievement.ResultsANOVA analysis showed a significant difference between birth length and height standard deviation scores (HSDS) at the different key ages (p<0.001), while no significant differences were found between HSDS measurements at 2, 5, and 10 years, at pubertal onset, and at AH. HSDS increased from −3.10 ± 0.84 to −2.31 ± 0.99 during rhGH treatment, with a total height gain of 0.79 ± 0.74, and no significant difference between untreated and treated NS at AH.ConclusionsrhGH treatment at the standard dose used for children with GH idiopathic deficiency is effective in improving growth and AH in NS with GHD. Further studies are needed to assess genotype-specific response to rhGH treatment in the different pathogenic variants of PTPN11 gene and in the less common genotypes.

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Section: Discussionsupporting

confidence: 79%

“…Furthermore, Seok et al. demonstrated an increase of HSDS and GV after 3 years of treatment in prepubertal NS children, with a similar response between NS and GHD patients ( 32 ). Malaquias et al.…”

Section: Discussionmentioning

confidence: 90%

Growth in Children With Noonan Syndrome and Effects of Growth Hormone Treatment on Adult Height

et al. 2021

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“…Up to 70% of NS subjects present with postnatal short stature ( 17 , 37 ), even though the majority has a normal birth weight and length ( 20 ); the presence of edema may result in an overestimation of weight which should be carefully evaluated ( 20 ). Some authors have reported a significantly higher frequency of NS subjects who are small for gestational age (SGA) compared with the general population (24%), particularly for length ( 24 ), and in specific genotypes ( 24 , 38 ). Attention should be paid to SGA patients whose phenotypic characteristics are suggestive of a RASopathy, and to children who do not respond to GH treatment ( 39 ).…”

Section: Growth and Growth Hormone-igf-1 Axis In Noonan Syndromementioning

confidence: 99%

“…Side effects in children were infrequently reported. Based on the data, rhGH treatment does not seem to influence cardiac physiology and function ( 38 ). The decision to use rhGH in patients with NS should, however, be made on a case-by-case basis ( 8 ).…”

Section: Overview Of Cautions and Side Effects During Rhgh Treatmentmentioning

confidence: 99%

Inside the Noonan “universe”: Literature review on growth, GH/IGF axis and rhGH treatment: Facts and concerns

Stagi

Ferrari

et al. 2022

Front. Endocrinol.

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Noonan syndrome (NS) is a disorder characterized by a typical facial gestalt, congenital heart defects, variable cognitive deficits, skeletal defects, and short stature. NS is caused by germline pathogenic variants in genes coding proteins with a role in the RAS/mitogen-activated protein kinase signaling pathway, and it is typically associated with substantial genetic and clinical complexity and variability. Short stature is a cardinal feature in NS, with evidence indicating that growth hormone (GH) deficiency, partial GH insensitivity, and altered response to insulin-like growth factor I (IGF-1) are contributing events for growth failure in these patients. Decreased IGF-I, together with low/normal responses to GH pharmacological provocation tests, indicating a variable presence of GH deficiency/resistance, in particular in subjects with pathogenic PTPN11 variants, are frequently reported. Nonetheless, short- and long-term studies have demonstrated a consistent and significant increase in height velocity (HV) in NS children and adolescents treated with recombinant human GH (rhGH). While the overall experience with rhGH treatment in NS patients with short stature is reassuring, it is difficult to systematically compare published data due to heterogeneous protocols, potential enrolment bias, the small size of cohorts in many studies, different cohort selection criteria and varying durations of therapy. Furthermore, in most studies, the genetic information is lacking. NS is associated with a higher risk of benign and malignant proliferative disorders and hypertrophic cardiomyopathy, and rhGH treatment may further increase risk in these patients, especially as dosages vary widely. Herein we provide an updated review of aspects related to growth, altered function of the GH/IGF axis and cell response to GH/IGF stimulation, rhGH treatment and its possible adverse events. Given the clinical variability and genetic heterogeneity of NS, treatment with rhGH should be personalized and a conservative approach with judicious surveillance is recommended. Depending on the genotype, an individualized follow-up and close monitoring during rhGH treatments, also focusing on screening for neoplasms, should be considered.

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“…About 70% of the patients with NS have short stature (7) although its exact mechanisms have not yet been defined. Multiple studies (8)(9)(10)(11)(12)(13) have shown the effectiveness of growth hormone (GH) treatment for these patients but it is not yet fully standardized.…”

Section: Introductionmentioning

confidence: 99%

Noonan syndrome patients with short stature at a single paediatric endocrinology centre

Deyanova

Iotova²,

Stoyanova³

et al. 2022

SSM

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INTRODUCTION: Noonan syndrome (NS) is caused by mutations in RAS/MAPK signalling pathway genes. Growth hormone (GH) treatment is an established yet not fully standardized treatment. AIM: The aim of this article is to assess the first 2 years of GH treatment in NS patients at a single centre. PATIENTS AND METHODS: A total of 20 (16 males) NS clinically diagnosed regularly followed patients participated (2011-2020). Of these, 9 (45%) had cardiac defects, and 8 (40%) had short stature. Growth hormone deficiency (GHD) was confirmed in 5 patients who started GH treatment, and 2 were treated as short, small for gestational age children. Patients underwent anthropometry, clinical, laboratory and imaging investigations. RESULTS: The mean age at NS diagnosis was 7.8±3.4 years (1.3÷10.5), and at GH start 9.1±1.5 years. At GH start, SDS height was -3.42±0.58 (-4.1÷-2.6), SDS weight -3.07±0.58 (-3.73÷-2.27), and SDS IGF1 -1.12±0.98 (-2.44÷0.25). The mean BA at diagnosis was delayed by 2.6 ± 0.9 years. The GH starting dose was 0.035±0.005 mg/kg/d, and changed little thereafter.The growth velocity for the 1 st year of treatment was 8.9±1.4 cm, and for the 2 nd year 6.9±1.1 cm. The first year ΔSDS height was 0.72 (p=0.002), ΔSDS weight was 0.83 (p=0.025), the 2 nd year increments being insignificant. The 1 st and 2 nd year ΔSDS IGF1 were 1.70 (p=0.007) and 0.25 (n.s.), resp. bone age remained significantly de-layed. No treatment side effects were observed.

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Effectiveness of growth hormone therapy in children with Noonan syndrome

Cited by 7 publications

References 26 publications

Growth in Children With Noonan Syndrome and Effects of Growth Hormone Treatment on Adult Height

Growth in Children With Noonan Syndrome and Effects of Growth Hormone Treatment on Adult Height

Inside the Noonan “universe”: Literature review on growth, GH/IGF axis and rhGH treatment: Facts and concerns

Noonan syndrome patients with short stature at a single paediatric endocrinology centre

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