Atypical ADPKD Due to a Pathogenic Variant: An Educational Case Report.

RATIONALE

Due to next-generation sequencing, variants in new genes such as are recently being identified as causing atypical autosomal dominant polycystic kidney disease (ADPKD). It is important to describe phenotypes associated with these variants in order to increase awareness among clinicians, especially since genetic variability affects ADPKD severity.

PRESENTING CONCERNS OF THE PATIENT

We describe a 55-year-old female patient of Haitian origin who presented with slowly deteriorating kidney function, microscopic hematuria, proteinuria, enlarged kidneys with innumerable small cysts, and a family history of chronic kidney disease and cysts. The phenotype was atypical for ADPKD caused by or variants, since cysts were of small size, kidneys were only moderately enlarged, and the patient had no extra-renal involvement suggestive of typical ADPKD such as liver cysts, pancreatic cysts, cranial aneurysms, or cardiac abnormalities.

DIAGNOSES

A panel of genes was analyzed by next-generation massive sequencing techniques, including , and . Genetic testing revealed a heterozygous variant in the gene (c.123 dup), which is predicted to result in premature protein termination (p. Lys42*) and was classified by the laboratory as likely pathogenic.

INTERVENTIONS

She was treated with candesartan 16 mg once daily to address her proteinuria.

OUTCOMES

At the time of the most recent follow-up, her proteinuria has increased, and her kidney function continues to slowly deteriorate.

TEACHING POINTS

variants are a rare cause of atypical ADPKD. It is important to recognize the clinical features that help distinguish from and variants. Atypical ADPKD due to variants is usually characterized by small cysts, normal kidney size, proteinuria, progressive chronic kidney disease, and phenotypic overlap with autosomal dominant tubulointerstitial kidney disease (ADTKD). It may, however, present itself with enlarged kidneys as was seen in our patient. Genetic testing should be offered whenever a patient presents atypical features of ADPKD, which also requires increased awareness among clinicians regarding the various phenotypes of atypical ADPKD.