[Noonan syndrome: from phenotype to growth hormone therapy].
Noonan Syndrome (NS) is one of the most common genetic syndromes and it is an important differential diagnosis in children with short stature, delayed puberty and cryptorchidism. NS is characterized by dysmorphic facial features, congenital heart defects and short stature, but there is a great variability in phenotype. NS may occur in a pattern consistent with autosomal dominant inheritance with almost complete penetrance. The diagnosis is based on a clinical score system proposed by van der Burgt e cols. in 1994. In recent years, germline mutations in the components of RAS-MAPK (mitogen activated protein kinase) pathway have been shown to be involved in the pathogenesis of NS. Mutations in PTPN11, KRAS, SOS1, RAF1 and MEK1 can explain 60-70% of NS molecular cause. Growth hormone therapy is proposed to correct the short stature observed in these patients. Recent studies suggest that the presence of PTPN11 mutations in patients with NS indicates a reduced growth response to short-term hrGH treatment. In this article, it is reviewed clinical and molecular aspects of NS and hrGH treatment for short stature.
Malaquias
Alexsandra C
AC
Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM/42, Faculdade de Medicina, Universidade de São Paulo, SP, Brazil.
Ferreira
Lize V
LV
Souza
Silvia C
SC
Arnhold
Ivo J P
IJ
Mendonça
Berenice B
BB
Jorge
Alexander A L
AA
D001827:Body Height / Q000235:genetics; D003937:Diagnosis, Differential; D005183:Failure to Thrive / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D019382:Human Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics; D009634:Noonan Syndrome / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D010641:Phenotype; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics; D011666:Pulmonary Valve Stenosis / Q000175:diagnosis
D019382:Human Growth Hormone; D020928:Mitogen-Activated Protein Kinases; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11