Diagnosis and Long-Term Human Growth Hormone Treatment of a Boy with Noonan Syndrome

Abstract

Noonan syndrome (NS) is a relatively common, clinically heterogeneous disorder, with an estimated incidence of 1:1,000 to 1:2,500 live births. It is characterized by proportionate postnatal short stature, dysmorphic facial features, chest deformities and congenital heart disease. This report describes a child with NS who harbors the N308D mutation in protein tyrosine phosphatase, nonreceptor type 11 (NM_002834; PTPN11) gene. Because of his short stature, poor growth rate and low levels of insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein 3 (IGFBP-3), recombinant human growth hormone (rhGH) therapy was initiated at 11.5 years. During the first year of therapy, the child remained prepubertal and had a significant increase in growth velocity (from 3.0 to 7.8 cm/year). Treatment was maintained throughout puberty, and after approximately 5 years of therapy, the subject still has a good growth velocity (7.6 cm/year) and his height is 0.5 standard deviation score (SDS) above pretreatment height. When the subject’s growth evolution is analyzed using an NS-specific growth chart, it is evident that his height increased almost 2 SD. During treatment, IGF-I and IGFBP-3 levels increased progressively and reached normal ranges for sex and age. Data strongly suggest that PTPN11 mutations identified in NS patients cause partial GH insensitivity. Long-term treatment with rhGH doses in this NS child with a PTPN11 mutation, in whom a partial postreceptor GH insensitivity was expected, normalized IGF-I and IGFBP-3 levels, improved growth velocity and increased his final height prediction.