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 language | English |
|---|---|
| Pages (from-to) | 2756-2761 |
| Number of pages | 6 |
| Journal | American Journal of Medical Genetics, Part A |
| Volume | 161 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 2013 |
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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 journal › Article
}
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 -