C-type natriuretic peptide (CNP) plasma levels are elevated in subjects with achondroplasia, hypochondroplasia, and thanatophoric dysplasia.

[achondroplasia]

Context : C-type natriuretic peptide (CNP ) is a crucial regulator of endochondral bone growth . In a previous report of a child with acromesomelic dysplasia , Maroteaux type (AMDM ), due to loss -of-function of the CNP receptor (NPR-B ), plasma levels of CNP were elevated . In vitro studies have shown that activation of the MEK /ERK MAP kinase pathway causes functional inhibition of NPR-B . Achondroplasia , hypochondroplasia , and thanatophoric dysplasia are syndromes of short-limbed dwarfism caused by activating mutations of fibroblast growth factor receptor-3 , which result in over-activation of the MEK /ERK MAP kinase pathway . Objective : To determine if these syndromes exhibit evidence of CNP resistance as reflected by increases of plasma CNP and its amino terminal propeptide (NTproCNP ). Design : This was a prospective , observational study . Subjects : Participants were 63 children and 20 adults with achondroplasia , 6 children with hypochondroplasia , 2 children with thanatophoric dysplasia , and 4 children and 1 adult with AMDM . Results : Plasma levels of CNP and NTproCNP were higher in children with achondroplasia with CNP SD scores (SDS ) of 1 .0 (0 .3 -1 .4 ) [median (intraquartile range )] and NTproCNP SDS of 1 .4 (0 .4 -1 .8 ) (p <0 .0005 ). NTproCNP levels correlated with height velocity . Levels were also elevated in adults with achondroplasia , CNP SDS 1 .5 (0 .7 -2 .1 ) and NTproCNP SDS 0 .5 (0 .1 -1 .0 ), p <0 .005 . In children with hypochondroplasia , CNP SDS were 1 .3 (0 .7 -1 .5 )(p =0 .08 ) and NTproCNP SDS were 1 .9 (1 .8 -2 .3 )(p <0 .05 ). In children with AMDM , CNP SDS were 1 .6 (1 .4 -3 .3 ) and NTproCNP SDS were 4 .2 (2 .7 -6 .2 ) (p <0 .01 ). Conclusions : In these skeletal dysplasias , elevated plasma levels of proCNP products suggest the presence of tissue resistance to CNP .

Diseases
Validation

Diseases presenting "which result in over-activation of the mek" symptom

achondroplasia

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