Genetic analysis diagnosed Bardet–Biedl syndrome in a patient with a clinical diagnosis of Senior–Løken syndrome

Abstract

Abstract Background Senior–Løken syndrome (SLS) and Bardet–Biedl syndrome (BBS) are ciliopathies. SLS is characterized by retinitis pigmentosa (RP) and familial nephronophthisis, leading to end-stage kidney disease, while BBS is characterized by six major symptoms: RP, polydactyly, obesity, genital abnormalities, learning difficulties, and renal defects. Ciliopathies have been diagnosed on a phenotypic basis, but diagnosis can now be established by genetic testing, using techniques such as next-generation sequencing. Here, we report a patient clinically diagnosed with SLS but diagnosed with BBS 13 years later using next-generation sequencing. Case presentation The patient was diagnosed with RP at the age of 6 years. She had some difficulty in social interactions and pre-obesity, but no polydactyly. At the age of 8 years, she was diagnosed with chronic kidney disease, anemia, and liver dysfunction. Kidney and liver biopsy revealed renal tubule cysts, tubule membrane disruption, and liver fibrosis. Therefore, SLS was diagnosed but no NPHP1 mutations were detected. Peritoneal dialysis was started at the age of 9 years, and she underwent kidney transplantation with a graft from her father at the age of 13 years. At the age of 21 years, she again underwent genetic testing for most of the mutations associated with ciliopathy. This revealed a homozygous frameshift mutation in intron 11 of SDCCAG8. Conclusions Mutations in SDCCAG8 are known to be causative of SLS and BBS without polydactyly. The fact that the patient had RP, some difficulty in social interactions, pre-obesity, juvenile nephronophthisis, liver fibrosis, bronchial asthma, and otitis media suggested BBS. However, some of these are not specific symptoms for BBS and she had few typical symptoms of BBS. Therefore, a definitive diagnosis of BBS was difficult without genetic analysis. Because many more patients with SDCCAG8 mutations have extrarenal manifestations like the current patient than standard nephronophthisis patients, careful monitoring of extrarenal manifestations is needed to improve patient management.

Keywords

• Ciliopathy
• Bardet–Biedl syndrome
• Senior–Løken syndrome
• SDCCAG8