Expanding the genetic spectrum of Noonan syndrome

Background: The autosomal-dominant Noonan syndrome (MIM 163950) is characterized by short stature, typical facial dysmorphology and heart defects. Noonan syndrome is genetically heterogeneous. Over the last few years, germline mutations in four genes have been found in people with clinical signs of Noonan syndrome, accounting for approximately 65% of cases. All four genes encode proteins involved in the Ras-mitogen-activated protein kinase pathway and result in upregulation of this pathway. Recently, more data on final height after long-term growth hormone (GH) therapy has become available that shows its effectiveness in increasing final height for individuals with Noonan syndrome. Conclusions: The genetics underlying Noonan syndrome has been partially clarified over the last 5 years and further findings will undoubtedly be reported in the next few years. GH therapy has been used to treat patients with Noonan syndrome for approximately 15 years and is effective in improving adult height in affected children.