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Although there is variability in presentation and new advances changing the life expectancy of affected individuals, it remains a disease with high morbidity and mortality, particularly when diagnosed prenatally.
Definition
Individuals affected with ARPKD typically have biallelic pathogenic variants in the PKHD1 gene on chromosome 6p21. These variants affect the production of fibrocystin, a protein found in the primary cilium or basal body complex of epithelial cells in the renal tubules and hepatic bile ducts.
As a result, affected individuals develop end-stage renal disease and hepatobiliary disease.
Ultrasound Findings
There is wide variability in the prenatal presentation of ARPKD. In some cases, enlarged hyperechoic kidneys with poor corticomedullary differentiation can be identified in the second trimester of pregnancy. Frequently, the kidneys are quite enlarged, ranging from 4 to 15 standard deviations above normal in size. In addition, oligohydramnios or anhydramnios are frequently present in ARPKD. In more subtle cases, mild enlargement and a hyperechoic cortical rim may be the only findings. In the third trimester of pregnancy, larger cysts >3 mm in size may develop. These cysts can be bilateral or unilateral. In some cases, no abnormality is identified prenatally (Figure).
Kidneys are enlarged, measuring 6.0 cm, and demonstrate typical loss of corticomedullary differentiation. Note the absence of amniotic fluid surrounding the fetus, which is consistent with oligohydramnios.
Society for Maternal-Fetal Medicine. SMFM Fetal Anomalies Consult Series #4. Am J Obstet Gynecol 2021.
Aside from oligohydramnios or anhydramnios and the resultant pulmonary hypoplasia, which can sometimes be suspected with ultrasonography, additional ultrasonographic anomalies are uncommon. Although hepatic fibrosis and biliary dysgenesis are common in affected patients, these findings are rarely identified prenatally.
Prenatal ultrasound, genotype, and outcome in a large cohort of prenatally affected patients with autosomal-recessive polycystic kidney disease and other hereditary cystic kidney diseases.
Bardet-Biedl syndrome is another ciliopathy that can present prenatally with enlarged cystic kidneys. Postaxial polydactyly is common in individuals with Bardet-Biedl syndrome and can help differentiate it from ARPKD. In addition, the renal parenchyma is typically more homogenous in individuals with Bardet-Biedl syndrome.
Meckel-Gruber syndrome is another rare autosomal recessive condition that can present with enlarged cystic kidneys; the cysts often appear earlier than in ARPKD. Postaxial polydactyly and central nervous system malformations are common with Meckel-Gruber syndrome.
Prenatal ultrasound, genotype, and outcome in a large cohort of prenatally affected patients with autosomal-recessive polycystic kidney disease and other hereditary cystic kidney diseases.
Prenatal diagnostic testing should be offered when ARPKD is suspected. In addition, chromosomal microarray analysis can be offered when prenatal diagnosis is performed, particularly in the presence of additional ultrasound findings, although it will not detect single-gene disorders, including ARPKD. Molecular genetic testing on tissue obtained by chorionic villus sampling or amniocentesis can be used to identify pathogenic variants in the PKHD1 gene. The presence of two pathogenic variants in this gene confirms the diagnosis of ARPKD. However, even in cases with strong histopathologic and clinical support for the diagnosis, variant detection rates range from 80% to 85%.
If there are additional anomalies, consanguinity, or a family history of a specific condition, gene panel testing or exome sequencing is sometimes useful.
Pregnancy and Delivery Management
Given the poor prognosis of individuals with prenatally identified ARPKD, particularly in the setting of early oligohydramnios or anhydramnios, patients with an affected fetus should be offered pregnancy termination. Parents who choose to continue their pregnancy should be offered comfort care for the neonate at the time of delivery. During pregnancy, serial ultrasound examinations can be useful to assess kidney size and amniotic fluid volume.
Consensus expert recommendations for the diagnosis and management of autosomal recessive polycystic kidney disease: report of an international conference.
Parents who desire full resuscitation should deliver at a center with a level IV neonatal intensive care unit. Because massive enlargement of the kidneys can result in an abdominal circumference that may preclude a vaginal delivery at term, cesarean delivery may be necessary.
There exists marked variability in the presentation and prognosis of ARPKD. Prenatally diagnosed ARPKD is associated with poorer outcomes than ARPKD identified in the neonatal period or childhood. Those with oligohydramnios or anhydramnios identified on prenatal ultrasound are at considerable risk of pulmonary hypoplasia and have an approximately 30% mortality rate within the first year of life.
In addition, it is reported that the genotype may have some association with phenotype and that individuals with truncating variants are more likely to have poor outcomes than those with missense variants.
Individuals who survive beyond the first month of life have a better prognosis, with reported survival rates at 10 years as high as 82%. However, these patients typically require dialysis and renal transplantation and frequently develop hypertension, hepatic fibrosis, and portal hypertension.
ARPKD is infrequently diagnosed on prenatal ultrasound. However, when it is identified, it is associated with significant morbidity and mortality. As an autosomal recessive disease with variable expressivity, parents and siblings of patients with affected pregnancies should be evaluated and counseled on their risks of also having an affected pregnancy.
Prenatal ultrasound, genotype, and outcome in a large cohort of prenatally affected patients with autosomal-recessive polycystic kidney disease and other hereditary cystic kidney diseases.
Consensus expert recommendations for the diagnosis and management of autosomal recessive polycystic kidney disease: report of an international conference.
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