Role of the natriuretic Peptide system in normal growth and growth disorders.

[achondroplasia]

The C-type natriuretic peptide (CNP ) and its receptor (NPR-B ) are recognized as important regulators of longitudinal growth . Animal models involving CNP or NPR-B genes (Nppc or Npr 2 ) support the fundamental role of CNP /NPR-B for endochondral ossification . Studies with these animals allow the development of potential drug therapies for dwarfism . Polymorphisms in two genes related to the CNP pathway have been implicated in height variability in healthy individuals . Biallelic loss -of-function mutations in NPR-B gene (NPR 2 ) cause acromesomelic dysplasia type Maroteux , a skeletal dysplasia with extremely short stature . Heterozygous mutations in NPR 2 are responsible for nonsyndromic familial short stature . Conversely , heterozygous gain-of-function mutations in NPR 2 cause tall stature , with a variable phenotype . A phase 2 multicenter and multinational trial is being developed to evaluate a CNP analog treatment for achondroplasia . Pediatricians and endocrinologists must be aware of growth disorders related to natriuretic peptides , although there is still much to be learned about its diagnostic and therapeutic use . Â© 2014 S . Karger AG , Basel .