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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

4/22/14 4:35 PM