Growth Response, Near-Adult Height, and Patterns of Growth and Puberty in Patients with Noonan Syndrome Treated with Growth Hormone

Romanò, Alicia; Dana, Ken; Bakker, Bert; Davis, D. Aaron; Hunold, Joanne Julius; Jacobs, Joan R.; Lippe, Barbara M.

doi:10.1210/jc.2008-2094

Cited by 100 publications

(141 citation statements)

References 24 publications

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“…Thus Kirk et al, observed a moderate increase in height SDS of 0.8 in 10 patients [22], which is in accordance with a rise of 0.87 in 24 patients reported by Raaijmakers et al, [29]. On the other hand, Osio et al, Noordam et al, and Romano et al, reported better outcomes of GH therapy, with increases in height SDS ranging from 1.3 to 1.7 on a total of 112 patients [26,28,30].…”

Section: Gh Therapy In Nssupporting

confidence: 64%

“…In addition to cardiac and neoplasic adverse effects, GH therapy could potentially interfere with bone homeostasis and with carbohydrate and lipid metabolism. Supporting this view, 6 cases of scoliosis were reported in a panel of 65 patients under GH therapy [30]. Nevertheless, it is important to consider that scoliosis is not rare in NS.…”

Section: Potential Adverses Effects Of Gh Therapymentioning

confidence: 89%

“…Despite these limitations, it is worthwhile to analyze the different reports which addressed this question [22][23][24][25][26][27][28][29][30][31]. Their data are summarized in Table 1.…”

Section: Gh Therapy In Nsmentioning

confidence: 99%

“…Indeed, an earlier initiation of treatment is thought to result in a better outcome, as longer duration of GH therapy during the prepubertal period was found to produced greater height gains [26,30]. It is also important to consider that the link between earlier start of GH therapy and optimal height gain has been also observed in other growth-related disorders, including Turner's syndrome [4,32].…”

Section: Gh Therapy In Nsmentioning

confidence: 99%

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Growth hormone and noonan syndrome: update in dysfunctional signaling aspects and in therapy for short stature

Raynal¹

2014

Horm Stud

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Short stature is a frequent feature of Noonan syndrome (NS), a disease caused by mutations of genes encoding components of the Ras/mitogen-activated protein kinases (MAPK) signalling pathway. To date numerous patients have been treated with growth hormone (GH) in various countries. However this treatment is still controversial, as its efficacy is a matter of debate. The final height gain of GH therapy represents 5 to 10 cm, at best, which is disappointing considering the length and burden of the treatment. The reasons explaining this lack of efficiency are poorly understood and they seemed to involve a waning effect after the first year of GH treatment or acceleration of bone maturation in patients on GH. Moreover, GH therapy raises questions about its safety, especially in subjects with NS who are at risk for cardiac defects and malignancies. Cases of severe adverse effects were described, yet too sporadically to conclude that they were certainly caused by GH therapy. Novels insights in understanding the dysfunction of GH-dependent processes in NS were recently reported and this manuscript aims at reviewing the latest advances. Clinical data suggested that growth retardation could be caused by a partial postreceptor resistance to GH, an impaired sensitivity to GH which could also explain the modest efficiency of GH therapy in NS patients. Similar observations were also obtained in a NS mouse model harboring a mutation in the gene encoding the tyrosine phosphatase Shp2. In the mouse, the mechanism of GH resistance is thought to involve upregulation by mutated Shp2 of GH-induced Ras/MAPK, a signaling pathway which seemed to play a negative regulatory role in the production of GH mediators involved in bone growth. Despite these recent finding, the underlying mechanisms of growth retardation and GH therapy in NS remain to be further explored in order to improve treatment for short stature.

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Section: Gh Therapy In Nssupporting

confidence: 64%

Section: Potential Adverses Effects Of Gh Therapymentioning

confidence: 89%

“…Despite these limitations, it is worthwhile to analyze the different reports which addressed this question [22][23][24][25][26][27][28][29][30][31]. Their data are summarized in Table 1.…”

Section: Gh Therapy In Nsmentioning

confidence: 99%

Section: Gh Therapy In Nsmentioning

confidence: 99%

See 2 more Smart Citations

Growth hormone and noonan syndrome: update in dysfunctional signaling aspects and in therapy for short stature

Raynal¹

2014

Horm Stud

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“…These studies have been focused on cohorts including patients with and without molecularly confirmed diagnosis, different genotypes, various age at enrollment, as well as different replacement therapy protocols. Therefore, the analysis of efficacy of GH treatment has provided contradictory results [Kirk et al, 2001;Osio et al, 2005;Otten and Noordam, 2007;Romano et al, 2009;Lee et al, 2012], and a mean height gain ranging between 0.6 and 2 SDS [Dahlgren, 2009].…”

Section: Discussionmentioning

confidence: 99%

GH Therapy and first final height data in Noonan‐like syndrome with loose anagen hair (Mazzanti syndrome)

Mazzanti

Tamburrino

Scarano

et al. 2013

American J of Med Genetics Pt A

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Noonan-like syndrome with loose anagen hair (NS/LAH or Mazzanti Syndrome) is caused by a single missense mutation in SHOC2 promoting tN-myristoylation of the encoded protein.Cardinal features include facial features resembling NS, short stature often associated with proven growth hormone deficiency (GHD), typical ectodermal anomalies, and distinctive behavior. Overall, the clinical features are more severe than those generally observed in NS, even though the phenotype improves with age. We report on growth and pubertal trend in seven patients heterozygous for a mutated SHOC2 allele, treated with longterm GH-therapy, and final height (FH) in three of them. They were approximately À3 SDS below the Italian general population standards, they had very low IGF1 levels at baseline and GHD at pharmacological tests. All patients were treated with GH (0.035 mg/kg/day) for a mean period of 8.49 AE 5.72 years. After the 1st year of GH-therapy, IGF1 level and height velocity had increased. Three of 7 patients reached the FH (À2.34 AE 0.12 SDS) at 18.25 AE 0.73 years, after GH administration for 12.39 AE 2.12 years. Pubertal development was variable, showing a prolonged and delayed puberty or rapid pubertal progression that could impair the FH. Overall, our data in this small cohort suggest that NS/LAH patients benefit from long-term GH-therapy, although they do not show the characteristic catch-up growth of isolated GHD. While the observed growth and pubertal behavior is consistent with a dysfunction of the hypothalamic-pituitarygonadal axis, the functional link between SHOC2 and the GH/ IGF signaling pathways remains to be clarified.

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Improved growth velocity of a patient with Noonan‐like syndrome with loose anagen hair (NS/LAH) without growth hormone deficiency by low‐dose growth hormone therapy

Takasawa

Takishima

Morioka

et al. 2015

American J of Med Genetics Pt A

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Noonan-like syndrome with loose anagen hair (NS/LAH; OMIM 607721) is caused by a heterozygous c.4A>G mutation in SHOC2. Most cases exhibit both growth hormone deficiency (GHD) and growth hormone insensitivity (GHI) and thus require a high dose of growth hormone (GH) therapy (e.g., 35-40 µg/kg/day). We report on a genetically diagnosed NS/LAH patient manifesting severe short stature (-3.85 SDs) with low serum level of IGF1, 30 ng/ml. The peak levels of GH stimulation tests were within the normal range, and GHI was not observed in the IGF1 generation test. However, with low-dose GH therapy (25 µg/kg/day) for two years, IGF1 level and height were remarkably improved (IGF1: 117 ng/ml, height SDs: -2.20 SDs). Further, catch-up of motor development and improvement of the proportion of extending limbs to trunk were observed (the Developmental Quotient score increased from 68 to 98 points, and the relative sitting height ratio decreased from 0.62 to 0.57). Our results suggest that endocrinological causes for short stature are variable in NS/LAH and that GH therapy should be considered as a possible treatment for delayed development in NS/LAH.

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Growth Response, Near-Adult Height, and Patterns of Growth and Puberty in Patients with Noonan Syndrome Treated with Growth Hormone

Cited by 100 publications

References 24 publications

Growth hormone and noonan syndrome: update in dysfunctional signaling aspects and in therapy for short stature

Growth hormone and noonan syndrome: update in dysfunctional signaling aspects and in therapy for short stature

GH Therapy and first final height data in Noonan‐like syndrome with loose anagen hair (Mazzanti syndrome)

Improved growth velocity of a patient with Noonan‐like syndrome with loose anagen hair (NS/LAH) without growth hormone deficiency by low‐dose growth hormone therapy

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