A Case of Siblings with End-Stage Kidney Disease and Retinal Degeneration Suggestive of Partial Alström Syndrome.

Introduction: Renal ciliopathy is a genetic disorder caused by abnormalities in primary cilia. Alström syndrome (AS) is a rare renal ciliopathy caused by mutations in the ALMS1 gene. The diagnostic criteria for AS include symptoms such as vision impairment, obesity, type 2 diabetes, hearing loss, and renal failure. The manifestations of these symptoms vary widely, making the diagnosis of AS difficult.

Case presentation: We report the case of a 31-year-old Japanese woman and her 1 year older brother with cone-rod dystrophy (retinal degeneration) and end-stage kidney disease (ESKD), who presented with a clinical course similar to that of AS. Exome sequencing revealed two shared missense variants in ALMS1: c.4334A>T in exon 8 and c.7976C>G in exon 10. In silico analysis suggested that c.4334A>T was likely benign, whereas c.7976C>G was interpreted as a variant of uncertain significance (VUS). A definitive diagnosis of AS could not be made because typical symptoms such as diabetes and obesity were absent. Renal pathological findings in the proband's brother showed tubulointerstitial nephritis and shortening of the proximal tubule cilia, consistent with the known pathological features of AS. The rare and shared clinical features observed in both siblings suggest that VUS is associated with a partial manifestation of AS.

Conclusion: Both siblings presented with two rare clinical features, cone-rod dystrophy and ESKD, at a young age and carried the same VUS in ALMS1, suggesting the possibility of a partial AS.