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Safe, accurate, prenatal diagnosis of thanatophoric dysplasia using ultrasound and free fetal DNA.
[achondroplasia]
To
improve
the
prenatal
diagnosis
of
thanatophoric
dysplasia
by
defining
the
change
in
fetal
size
across
gestation
and
the
frequency
of
sonographic
features
,
and
developing
non-invasive
molecular
genetic
diagnosis
based
on
cell-free
fetal
DNA
(
cffDNA
)
in
maternal
plasma
.
Fetuses
with
a
confirmed
diagnosis
of
thanatophoric
dysplasia
were
ascertained
,
records
reviewed
,
sonographic
features
and
measurements
determined
.
Charts
of
fetal
size
were
then
constructed
using
the
LMS
(
lambda-
mu
-sigma
)
method
and
compared
with
charts
used
in
normal
pregnancies
and
those
complicated
by
achondroplasia
.
Cases
in
this
cohort
referred
to
our
Regional
Genetics
Laboratory
for
molecular
diagnosis
using
cffDNA
were
identified
and
results
reviewed
.
Forty
-
two
cases
were
scanned
in
our
units
.
Commonly
reported
sonographic
features
were
very
short
and
sometimes
bowed
femora
,
frontal
bossing
,
cloverleaf
skull
,
short
fingers
,
a
small
chest
and
polyhydramnios
.
Limb
shortening
was
obvious
from
as
early
as
13
weeks
'
gestation
,
with
minimal
growth
after
20
 
weeks
.
Analysis
of
cffDNA
in
three
of
these
pregnancies
confirmed
the
presence
of
the
c
.
742
C
>
CT
(
p
.
Arg
248
Cys
)
or
the
c
.
1948
A
>
AG
(
p
.
Lys
650
Glu
)
mutation
in
the
fibroblast
growth
factor
receptor
3
gene
.
T
hese
data
should
improve
the
accuracy
of
the
sonographic
diagnosis
of
thanatophoric
dysplasia
and
have
implications
for
reliable
and
safe
targeted
molecular
confirmation
using
cffDNA
.
Diseases
Validation
Diseases presenting
"prenatal diagnosis"
symptom
22q11.2 deletion syndrome
achondroplasia
adrenomyeloneuropathy
alexander disease
alpha-thalassemia
aromatase deficiency
benign recurrent intrahepatic cholestasis
cadasil
canavan disease
classical phenylketonuria
cohen syndrome
congenital adrenal hyperplasia
congenital diaphragmatic hernia
congenital toxoplasmosis
cystinuria
dentinogenesis imperfecta
epidermolysis bullosa simplex
harlequin ichthyosis
holt-oram syndrome
homocystinuria without methylmalonic aciduria
hydrocephalus with stenosis of the aqueduct of sylvius
junctional epidermolysis bullosa
kindler syndrome
krabbe disease
lamellar ichthyosis
megacystis-microcolon-intestinal hypoperistalsis syndrome
monosomy 21
neonatal adrenoleukodystrophy
oculocutaneous albinism
omenn syndrome
phenylketonuria
primary hyperoxaluria type 1
pyruvate dehydrogenase deficiency
severe combined immunodeficiency
wolf-hirschhorn syndrome
x-linked adrenoleukodystrophy
zellweger syndrome
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