Hypertrophic osteoarthropathy, primary, autosomal recessive, 2

PHOAR2-enteropathy syndrome (PHOAR2E) is characterized by primary hypertrophic osteoarthropathy (PHO) and/or chronic nonspecific ulcers (CNSU) of the small intestine. The cardinal features of PHO are digital clubbing, pachydermia, and periostosis; other manifestations include swelling and pain of the large joints, hyperhidrosis, seborrhea, and acne. CNSU often presents with chronic unexplained anemia and abdominal pain, and patients may exhibit edema due to hypoalbuminemia. Radiologic imaging or endoscopy shows multiple small ulcers, predominantly in the ileum, although the stomach, duodenum, and jejunum are often involved. PHO is more frequent and more severe in male patients, who often also report watery diarrhea, whereas CNSU is more often diagnosed in female patients, who may also show features of PHO such as digital clubbing or arthralgias and swelling of the joints. The same mutations in the SLCO2A1 gene have been reported in patients presenting with either diagnosis, and presumed sex-related modifiers of the manifestations of disease or other genotype/phenotype correlates have yet to be elucidated (Li et al., 2017; Umeno et al., 2018; Hong et al., 2022; Kimball et al., 2024). For a discussion of genetic heterogeneity of PHO, see PHOAR1 (259100). [from OMIM]