**7. Lack of CNP signaling in growth plate causes short stature and dwarfism**

Heterozygous carriers of a mutation in NPR-B, the receptor for CNP, have idiopathic short stature suggesting a quantitative effect of the CNP pathway on skeletal growth [66]. Serum levels of CNP's N-terminal pro-peptide (NT-proCNP), the inactive form of CNP, were found to be highest at birth, gradually decreased by puberty, and plateau after 18 years of age [67]. The levels of NT-proCNP correlate with levels of alkaline phosphatase (bone formation markers) in humans [67, 68]. More importantly, serum NT-proCNP levels are maintained at a level in adults.

Individuals with acromesomelic dysplasia-type Maroteaux (AMDM), a type of human dwarfism, develop periarticular osteopenia, loss of trabecular bone structure. AMDM is caused by loss of function mutations in the CNP's receptor, natriuretic peptide-B (Npr2 gene). AMDM patients have disproportional growth retardation and abnormal development of bone tissue and appear to have (juxta-articular) metaphyseal flaring and osteopenia but do not have any other health problems [58, 69]. The trabecular bone loss is more significant in the juxtaarticular area resembling osteopenia of inflammatory arthritis.
