Growth hormone therapy in patients with Noonan syndrome
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Noonan syndrome (NS) is an autosomal dominant disorder that involves multiple organ systems, with short stature as the most common presentation (>70%). Possible mechanisms of short stature in NS include growth hormone (GH) deficiency, neurosecretory dysfunction, and GH resistance. Accordingly, GH therapy has been carried out for NS patients over the last three decades, and multiple studies have reported acceleration of growth velocity (GV) and increase of height standard deviation score (SDS) in both prepubertal and pubertal NS patients upon GH therapy. One year of GH therapy resulted in almost doubling of GV compared with baseline; afterwards, the increase in GV gradually decreased in the following years, showing that the effect of GH therapy wanes over time. After four years of GH therapy, ~70% of NS patients reached normal height considering their age and sex. Early initiation, long duration of GH therapy, and higher height SDS at the onset of puberty were associated with improved final height, whereas gender, dosage of GH, and the clinical severity did not show significant association with final height. Studies have reported no significant adverse events of GH therapy regarding progression of hypertrophic cardiomyopathy, alteration of metabolism, and tumor development. Therefore, GH therapy is effective for improving height and GV of NS patients; nevertheless, concerns on possible malignancy remains, which necessitates continuous monitoring of NS patients receiving GH therapy.
Abstract
Noonan syndrome (NS) is an autosomal dominant disorder that involves multiple organ systems, with short stature as the most common presentation (>70%). Possible mechanisms of short stature in NS include growth hormone (GH) deficiency, neurosecretory dysfunction, and GH resistance. Accordingly, GH therapy has been carried out for NS patients over the last three decades, and multiple studies have reported acceleration of growth velocity (GV) and increase of height standard deviation score (SDS) in both prepubertal and pubertal NS patients upon GH therapy. One year of GH therapy resulted in almost doubling of GV compared with baseline; afterwards, the increase in GV gradually decreased in the following years, showing that the effect of GH therapy wanes over time. After four years of GH therapy, ~70% of NS patients reached normal height considering their age and sex. Early initiation, long duration of GH therapy, and higher height SDS at the onset of puberty were associated with improved final height, whereas gender, dosage of GH, and the clinical severity did not show significant association with final height. Studies have reported no significant adverse events of GH therapy regarding progression of hypertrophic cardiomyopathy, alteration of metabolism, and tumor development. Therefore, GH therapy is effective for improving height and GV of NS patients; nevertheless, concerns on possible malignancy remains, which necessitates continuous monitoring of NS patients receiving GH therapy.
참고문헌 (33)
- Mendez HM, "Noonan syndrome: a review", Am J Med Genet, 21, pp.493~506 (1985)
- Digilio MC, "Grouping of multiple-lentigines", LEOPARD and Noonan syndromes on the PTPN11 gene, 2002, pp.71, 389~394
- Nava C, "Cardio-facio-cutaneous and Noonan syndromes due to mutations in the RAS", MAPK signalling pathway:genotype-phenotype relationships and overlap with Costello syndrome, 2007, pp.44, 763~771
- Aoki Y, "The RAS", MAPK syndromes: novel roles of the RAS pathway in human genetic disorders, 2008, pp.29, 992~1006
- Jorge AA, "Noonan syndrome and related disorders: a review of clinical features and mutations in genes of the RAS", MAPK pathway, 2009, pp.71, 185~193
- Lee BH, "Spectrum of mutations in Noonan syndrome and their correlation with phenotypes", J Pediatr, 159, pp.1029~1035 (2011)
- Roberts AE, "Noonan syndrome", Lancet, 381, pp.333~342 (2013)
- Malumbres M, "RAS oncogenes: the first 30years", Nat Rev Cancer, 3, pp.459~465 (2003)
- Giehl K, "Oncogenic Ras in tumour progression and metastasis", Biol Chem, 386, pp.193~205 (2005)
- Ko JM, "PTPN11, SOS1, KRAS, and RAF1 gene analysis, and genotype-phenotype correlation in Korean patients with Noonan syndrome", J Hum Genet, 53, pp.999~1006 (2008)
- Cordeddu V, "Mutation of SHOC2 promotes aberrant protein N-myristoylation and causes Noonan-like syndrome with loose anagen hair", Nat Genet, 41, pp.1022~1026 (2009)
- Ranke MB, "Noonan syndrome: growth and clinical manifestations in 144 cases", Eur J Pediatr, 148, pp.220~227 (1988)
- Shaw AC, "The natural history of Noonan syndrome: a long-term followup study", Arch Dis Child, 92, pp.128~132 (2007)
- Binder G, "Health and quality of life in adults with Noonan syndrome", J Pediatr, 161, pp.501~505 (2012)
- Romano AA, "Growth hormone treatment in Noonan syndrome: the National Cooperative Growth Study experience", J Pediatr, 128(5Pt 2), pp.S18~S21 (1996)
- Tamburrino F, "Response to long-term growth hormone therapy in patients affected by RASopathies and growth hormone deficiency: patterns of growth, puberty and final height data", Am J Med Genet A, 167A, pp.2786~2794 (2015)
- Noordam C, "Growth hormone (GH)secretion in children with Noonan syndrome: frequently abnormal without consequences for growth or response to GH treatment", Clin Endocrinol (Oxf), 54, pp.53~59 (2001)
- Ferreira LV, "PTPN11 (protein tyrosine phosphatase, nonreceptor type11) mutations and response to growth hormone therapy in children with Noonan syndrome", J Clin Endocrinol Metab, 90, pp.5156~5160 (2005)
- Limal JM, "Noonan syndrome: relationships between genotype, growth, and growth factors", J Clin Endocrinol Metab, 91, pp.300~306 (2006)
- Cotterill AM, "The short-term effects of growth hormone therapy on height velocity and cardiac ventricular wall thickness in children with Noonan's syndrome", J Clin Endocrinol Metab, 81, pp.2291~2297 (1996)
- Choi JH, "Response to growth hormone therapy in children with Noonan syndrome: correlation with or without PTPN11gene mutation", Horm Res Paediatr, 77, pp.388~393 (2012)
- MacFarlane CE, "Growth hormone therapy and growth in children with Noonan's syndrome: results of 3 years' follow-up", J Clin Endocrinol Metab, 86, pp.1953~1956 (2001)
- Insook Jeong, "Long-term efficacy of recombinant human growth hormone therapy in short-statured patients with Noonan syndrome", Annals of Pediatric Endocrinology & Metabolism, 21(1), pp.26~30 (2016), 대한소아내분비학회
- Lee PA, "Effect of 4 years of growth hormone therapy in children with Noonan syndrome in the American Norditropin Studies: Web-Enabled Research (ANSWER) Program® registry.", Int J Pediatr Endocrinol, 2012, pp.15~ (2012)
- Noordam C, "Long-term GH treatment improves adult height in children with Noonan syndrome with and without mutations in protein tyrosine phosphatase, nonreceptor-type 11", Eur J Endocrinol, 159, pp.203~208 (2008)
- Romano AA, "Growth response, near-adult height, and patterns of growth and puberty in patients with noonan syndrome treated with growth hormone", J Clin Endocrinol Metab, 94, pp.2338~2344 (2009)
- Osio D, "Improved final height with long-term growth hormone treatment in Noonan syndrome", Acta Paediatr, 94, pp.1232~1237 (2005)
- Raaijmakers R, "Response to growth hormone treatment and final height in Noonan syndrome in a large cohort of patients in the KIGS database", J Pediatr Endocrinol Metab, 21, pp.267~273 (2008)
- Noordam K, "The relationship between clinical severity of Noonan's syndrome and growth, growth hormone (GH) secretion and response to GH treatment", J Pediatr Endocrinol Metab, 15, pp.175~180 (2002)
- Binder G, "PTPN11mutations are associated with mild growth hormone resistance in individuals with Noonan syndrome", J Clin Endocrinol Metab, 90, pp.5377~5381 (2005)
- Noordam C, "Effects of growth hormone treatment on left ventricular dimensions in children with Noonan's syndrome", Horm Res, 56, pp.110~113 (2001)
- Jongmans MC, "Cancer risk in patients with Noonan syndrome carrying a PTPN11mutation", Eur J Hum Genet, 19, pp.870~874 (2011)
- McWilliams GD, "Occurrence of DNET and other brain tumors in Noonan syndrome warrants caution with growth hormone therapy", Am J Med Genet A, 170A, pp.195~201 (2016)