Phenotypic Variability in Siblings With Autosomal Recessive Polycystic Kidney Disease

A decision‐making framework for genomic testing in paediatric nephrology

“…Advances in technologies and knowledge are achieved through research, and the participation of individuals with genetic disease can inform the care of future generations. For example, a confirmed genotype can facilitate inclusion in genotype‐specific registries such as ARegPKD, which in the future will provide variant‐specific prognostic information 21 …”

“…For example, a confirmed genotype can facilitate inclusion in genotype-specific registries such as ARegPKD, which in the future will provide variant-specific prognostic information. 21 Four case studies which represent common clinical scenarios where genetic testing could be considered were also developed. These case studies were used to explore the utility of the framework for paediatric nephrologists and were iteratively refined based on their comments and questions.…”

The Enigma of Clinical Heterogeneity Among Autosomal Recessive Polycystic Kidney Disease Siblings: PKHD1 Genotype Versus Other Genomic or Environmental Modifier

“…Overall, the data presented by Ajiri et al 8 provide a valuable longitudinal follow-up for both concordant and discordant courses in ARPKD families. It seems that survival of the neonatal period remains the key determinant of ARPKD severity and that differences in disease course are less likely to be found in families with biallelic PKHD1 truncating/loss-offunction changes associated with severe ARPKD leading to perinatal/ neonatal mortality.…”

“…The minimal clinical variability among ARPKD siblings as found by Ajiri et al 8 suggests that the underlying PKHD1 genotype has a substantial influence on the clinical course of the disease in childhood and adolescence. However, with being a registry study of predominantly tertiary care nephrology centers, there could be an underrepresentation of the more severe cases with perinatal death, the milder cases not requiring kidney replacement therapy, or cases with predominant hepatic phenotype.…”

“…It seems that survival of the neonatal period remains the key determinant of ARPKD severity and that differences in disease course are less likely to be found in families with biallelic PKHD1 truncating/loss-offunction changes associated with severe ARPKD leading to perinatal/ neonatal mortality. In addition, the data from Ajiri et al 8 suggest substantial consistency in the clinical course among ARPKD sibships surviving the neonatal period. However, in light of all published ARPKD sibling cohorts, to date, it remains that vigilant care is needed when counseling families with 1 affected child who are planning to conceive or are expecting a second child.…”