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

Laura Mazzanti, Federica Tamburrino, Emanuela Scarano, Annamaria Perri, Benedetta Vestrucci, Monica Guidetti, Cesare Rossi, Marco Tartaglia

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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 long-term GH-therapy, and final height (FH) in three of them. They were approximately -3 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 (0.035mg/kg/day) for a mean period of 8.49±5.72 years. After the 1st year of GH-therapy, IGF1 level and height velocity had increased. Three of 7 patients reached the FH (-2.34±0.12 SDS) at 18.25±0.73 years, after GH administration for 12.39±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-pituitary-gonadal axis, the functional link between SHOC2 and the GH/IGF signaling pathways remains to be clarified.

Original languageEnglish
Pages (from-to)2756-2761
Number of pages6
JournalAmerican Journal of Medical Genetics, Part A
Volume161
Issue number11
DOIs
Publication statusPublished - Nov 2013

Fingerprint

Loose Anagen Hair Syndrome
Growth Hormone
Growth
Pituitary Dwarfism
Delayed Puberty
Missense Mutation
Therapeutics
Alleles
Pharmacology
Phenotype
Noonan-Like Syndrome With Loose Anagen Hair
Population
Proteins

Keywords

  • Growth hormone
  • Noonan syndrome
  • NS/LAH
  • Rasopathies
  • SHOC2

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

GH Therapy and first final height data in Noonan-like syndrome with loose anagen hair (Mazzanti syndrome). / Mazzanti, Laura; Tamburrino, Federica; Scarano, Emanuela; Perri, Annamaria; Vestrucci, Benedetta; Guidetti, Monica; Rossi, Cesare; Tartaglia, Marco.

In: American Journal of Medical Genetics, Part A, Vol. 161, No. 11, 11.2013, p. 2756-2761.

Research output: Contribution to journalArticle

Mazzanti, Laura ; Tamburrino, Federica ; Scarano, Emanuela ; Perri, Annamaria ; Vestrucci, Benedetta ; Guidetti, Monica ; Rossi, Cesare ; Tartaglia, Marco. / GH Therapy and first final height data in Noonan-like syndrome with loose anagen hair (Mazzanti syndrome). In: American Journal of Medical Genetics, Part A. 2013 ; Vol. 161, No. 11. pp. 2756-2761.
@article{b913dd2127b2491495047ddece85f584,
title = "GH Therapy and first final height data in Noonan-like syndrome with loose anagen hair (Mazzanti syndrome)",
abstract = "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 long-term GH-therapy, and final height (FH) in three of them. They were approximately -3 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 (0.035mg/kg/day) for a mean period of 8.49±5.72 years. After the 1st year of GH-therapy, IGF1 level and height velocity had increased. Three of 7 patients reached the FH (-2.34±0.12 SDS) at 18.25±0.73 years, after GH administration for 12.39±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-pituitary-gonadal axis, the functional link between SHOC2 and the GH/IGF signaling pathways remains to be clarified.",
keywords = "Growth hormone, Noonan syndrome, NS/LAH, Rasopathies, SHOC2",
author = "Laura Mazzanti and Federica Tamburrino and Emanuela Scarano and Annamaria Perri and Benedetta Vestrucci and Monica Guidetti and Cesare Rossi and Marco Tartaglia",
year = "2013",
month = "11",
doi = "10.1002/ajmg.a.36255",
language = "English",
volume = "161",
pages = "2756--2761",
journal = "American Journal of Medical Genetics, Part A",
issn = "1552-4825",
publisher = "Wiley-Liss Inc.",
number = "11",

}

TY - JOUR

T1 - GH Therapy and first final height data in Noonan-like syndrome with loose anagen hair (Mazzanti syndrome)

AU - Mazzanti, Laura

AU - Tamburrino, Federica

AU - Scarano, Emanuela

AU - Perri, Annamaria

AU - Vestrucci, Benedetta

AU - Guidetti, Monica

AU - Rossi, Cesare

AU - Tartaglia, Marco

PY - 2013/11

Y1 - 2013/11

N2 - 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 long-term GH-therapy, and final height (FH) in three of them. They were approximately -3 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 (0.035mg/kg/day) for a mean period of 8.49±5.72 years. After the 1st year of GH-therapy, IGF1 level and height velocity had increased. Three of 7 patients reached the FH (-2.34±0.12 SDS) at 18.25±0.73 years, after GH administration for 12.39±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-pituitary-gonadal axis, the functional link between SHOC2 and the GH/IGF signaling pathways remains to be clarified.

AB - 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 long-term GH-therapy, and final height (FH) in three of them. They were approximately -3 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 (0.035mg/kg/day) for a mean period of 8.49±5.72 years. After the 1st year of GH-therapy, IGF1 level and height velocity had increased. Three of 7 patients reached the FH (-2.34±0.12 SDS) at 18.25±0.73 years, after GH administration for 12.39±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-pituitary-gonadal axis, the functional link between SHOC2 and the GH/IGF signaling pathways remains to be clarified.

KW - Growth hormone

KW - Noonan syndrome

KW - NS/LAH

KW - Rasopathies

KW - SHOC2

UR - http://www.scopus.com/inward/record.url?scp=84886245228&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84886245228&partnerID=8YFLogxK

U2 - 10.1002/ajmg.a.36255

DO - 10.1002/ajmg.a.36255

M3 - Article

C2 - 24124081

AN - SCOPUS:84886245228

VL - 161

SP - 2756

EP - 2761

JO - American Journal of Medical Genetics, Part A

JF - American Journal of Medical Genetics, Part A

SN - 1552-4825

IS - 11

ER -