h
ErEDitary
PolyCyStiC
kiDnEy
DiSEaSE
:
gEnEtiC
DiagnoSiS
anD
CounSEling
r
Ev
a
SSoC
m
ED
B
raS
2014; 60(2):98-102
99
ground. In the absence of other malformations, the main
diagnosis remains ARPKD or Adpkd.
I
N
PRENATAL
AND
NEONATAL
CONTEXT
,
IF
THE
RESULT
OF
THE
ULTRASOUND
IS
INCONCLUSIVE
,
DOES
HISTOPATHOLOGY
ALLOW
TO
REACH
A
DEFINITIVE
CONCLUSION
?
Pathological examinations performed during autopsy
in patients affected with severe nephropathy (subgroup
of 40%) conirmed the diagnosis of ARPKD (
C
) (
D
).
4,5
Dilation and hyperplasia of collecting duct are obser-
ved, which may appear cystic, without involvement of
the nephron.
ARPKD invariably occurs with biliary dysgenesis (
B
)
(
D
).
5,6
The intrahepatic bile ducts dilate and increase in
number with subsequent development of periportal ibro-
sis. This clinical picture, called congenital hepatic ibro-
sis, is essential for the diagnosis of ARPKD, even though
it is not a pathognomonic sign. Portal hypertension is a
common sequel, which evidence can be obtained through
ultrasonography.
In patients affected with milder ARPKD (the sub-
group of 60%), the clinical course is variable and signs of
portal hypertension may prevail. Liver biopsy should the-
refore be considered in these cases (
C
).
7,8
Recommendation
It is essential to try to establish the diagnosis using ana-
tomopathological examination when the ultrasound is
not informative to allow genetic counseling.
I
N
THE
CONTEXT
OF
A
YOUNG
ADULT
,
THE
ULTRASOUND
EXAMINATION
IS
SUFFICIENT
TO
CONFIRM
THE
CLINICAL
DIAGNOSIS
OF
ARPKD
IN
A
PATIENT
?
Patients affected with ARPKD who survive to (and th-
roughout) adolescence tend to develop primarily liver and
biliary impairment with less renal involvement. Hepatos-
plenomegaly, portal hypertension and Caroli disease, in
the presence of systemic hypertension and renal failure,
serve to conirm the diagnosis (
C
).
9
In these cases, the kid-
ney may be reduced in size (
C
).
10
Recommendation
The signs listed can establish the diagnosis. When incon-
sistencies among clinical signs persist, the anatomopa-
thological examination by means of liver biopsy should
be performed.
I
N
THE
CONTEXT
OF
AN
ADULT
,
IF
THE
RESULT
OF
THE
ULTRASOUND
EXAMINATION
IS
INCONCLUSIVE
,
DOES
THE MOLECULAR
TEST
ALLOW
TO
REACH
A
DEFINITIVE
CONCLUSION
?
Molecular tests can be direct (such as gene sequencing
PKHD1) or indirect, using linkage analysis (
C
),
11
which
depends on the possibility of analyzing a minimum num-
ber of family members known to be affected and unaf-
fected - which is not always feasible. Direct molecular ge-
netic tests cannot detect all mutations causing ARPKD,
so that the detection rate is around 80% or less when the
disease is milder (
C
).
12,13
Occasionally, the patient may
inherit two low penetrance mutations (hypomorphic) in
both copies of the PKD1 (or PKD2) gene, thus showing
a phenotype that is very similar to neonatal ARPKD, which
makes the molecular test even more necessary (
C
).
14
Recommendation
Despite its limitations, molecular tests can be performed
to try to conirm the diagnosis and to document at least
one of the disease-causing mutations. The type and po-
sition of mutations in the PKHD1 gene provide informa-
tion about the prognosis of the disease (
C
).
15
W
HAT
IS
THE
ROLE
OF MOLECULAR
TESTING
FOR
GENETIC
COUNSELING
OF
A
COUPLE
OR
A
FAMILY
TRANSMITTING
ARPKD
?
Molecular tests are the only ones able to provide predic-
tive information about ARPKD in individuals before the
clinical signs and symptoms develop. In some families,
the disease has a different progression among affected
siblings and molecular test can determine if a brother
with mild signs is affected or not (
C
).
8,15
Since a high
percentage of individuals affected with ARPKD survive
until (and throughout) adolescence, molecular tests al-
low to identify them prior to onset of symptoms. In the-
se individuals, the veriication of the effects of hyper-
tension and portal hypertension enables treatment,
prolonging life (
C
).
16
Recommendation
Pre-test counseling is required to explain the implications
of the results that will be obtained in the tests and to clari-
fy the limitations inherent to the method. After proper con-
sideration, family members are tested, with continued post-
-test counseling. A couple transmitting ARPKD that wants
to prevent the disease in future children needs to perform
these tests, anticipating their application in prenatal or preim-
SCIELO BOOK.indb 99
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