Describing the First Canadian Cohort of Oculogastrointestinal Neurodevelopmental Syndrome Caused by CAPN15 Pathogenic Variants

ABSTRACT Oculogastrointestinal neurodevelopmental syndrome (OGIN; OMIN #619318) is a rare autosomal recessive disorder resulting from pathogenic variants in the CAPN15 gene. OGIN syndrome has been previously seen to affect many different body systems and has been described to cause coloboma, imperforate anus, structural cardiac defects, and horseshoe kidneys. There is still little information about the phenotypic spectrum of this disease. This case series aims to describe the phenotypic spectrum and development of affected individuals. Our study includes eight patients—five patients previously described, and three newly identified patients from centers in Ontario and Quebec ranging from three to 15 years of age. All the French‐Canadian patients in our cohort were homozygous for the c. 1838C>T (p. Ser613Leu) variant. We also describe a non‐French‐Canadian patient who is compound heterozygous for the variants c.1957G>A (p. Gly653Ser) (paternally inherited) and c.2520delC p. Val841Trpfs133 (maternally inherited). Through this cohort, we describe some rare manifestations of OGIN syndrome; all four female patients had vaginal fistulae, and four of the patients had sensorineural hearing loss. All eight patients had pancreatic insufficiency requiring pancreatic enzyme replacement. More research is needed to investigate the genotype–phenotype correlation, as well as assess long‐term complications and natural history of the disease.