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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
.
©
2014
S
.
Karger
AG
,
Basel
.
Diseases
Validation
Diseases presenting
"tall stature"
symptom
achondroplasia
aromatase deficiency
cohen syndrome
This symptom has already been validated