Bardet–Biedl Syndrome Presenting with End-Stage Kidney Disease: A Case Report

Abstract

Background: Bardet–Biedl syndrome (BBS) is a rare autosomal-recessive ciliopathy characterised by retinal dystrophy, postaxial polydactyly, hypogonadism, obesity, neurodevelopmental abnormalities, and renal involvement. Renal disease is heterogeneous and may progress to advanced chronic kidney disease or kidney failure. We report a 17-year-old boy with characteristic syndromic features who presented with musculoskeletal symptoms and severe renal dysfunction. Bilateral small kidneys precluded renal biopsy, and whole-exome sequencing identified a homozygous likely pathogenic LZTFL1 variant consistent with BBS17. Case Presentation: A 17-year-old boy, the only child of a non-consanguineous marriage, presented with bilateral lower-limb bone pain, difficulty walking, decreased appetite, nausea, and generalised weakness. He had delayed developmental milestones, polydactyly, absent axillary and pubic hair with hypogonadism, and clinical features of retinal dystrophy. Investigations demonstrated severe kidney dysfunction (blood urea 183 mg/dL; serum creatinine 9.4 mg/dL), anaemia (haemoglobin 9.3 g/dL), hypoalbuminaemia (2.8 g/dL), hypocalcaemia (7.8 mg/dL), elevated alkaline phosphatase (194 IU/L), and elevated intact parathyroid hormone (328 pg/mL). Ultrasonography demonstrated bilaterally small kidneys with reduced cortical thickness. Fundus examination showed pale optic discs with atypical retinitis pigmentosa, while audiological evaluation revealed mild sensorineural hearing loss. Renal biopsy was not performed because of markedly reduced renal size. Whole-exome sequencing identified a homozygous LZTFL1 c.322C>T (p.Arg108Ter) variant, classified by the testing laboratory as likely pathogenic and consistent with BBS17. Conclusion: Severe kidney disease may be a prominent manifestation of BBS17. In a young patient with polydactyly, hypogonadism, retinal dystrophy, and renal dysfunction, recognition of the syndromic phenotype can guide genetic testing when renal biopsy is unsuitable and can facilitate multidisciplinary surveillance, genetic counselling, and timely kidney replacement planning.