Background: Johanson–Blizzard syndrome (JBS) is a rare autosomal recessive disorder caused by mutations in the Ubiquitin Protein Ligase E3 Component N-Recognin 1 (UBR1) gene, characterised by exocrine pancreatic insufficiency, craniofacial anomalies, endocrine dysfunction, hearing loss, and genitourinary abnormalities.

Case Report: We report the case of a young girl diagnosed in infancy with JBS following recognition by characteristic craniofacial features, cutis aplasia, ambiguous genitalia, and failure to thrive. Genetic testing confirmed a homozygous UBR1 mutation. Multisystem evaluation revealed growth hormone deficiency, hypothyroidism, profound sensorineural hearing loss, anorectal malformation and genitourinary abnormalities. Management included pancreatic enzyme replacement, nutritional supplementation, cochlear implantation, thyroid and growth hormone therapy, and staged genitourinary reconstructive surgeries. She remains on a close developmental, renal, and endocrine follow-up.

Conclusion: This case highlights few rare associations in JBS, the importance of comprehensive multidisciplinary care and long-term follow-up in these children to optimise functional outcomes and mitigate complications.