Background: The genetics of syndromic hidradenitis suppurativa (HS), an immune-mediated condition associated with systemic comorbidities such as inflammatory bowel diseases and arthritis, has not been completely elucidated.
Objective: To describe clinical features and genetic signature of patients with the main syndromic HS forms, i.e., PASH, PAPASH, and PASH/SAPHO overlapping.
Methods: Whole-exome sequencing (WES) approach was performed in ten patients with syndromic HS.
Results: Three clinical settings have been identified based on presence/absence of gut and joint inflammation. Four PASH patients who had also gut inflammation showed three different variants in NOD2 gene, two variants in OTULIN, and a variant in GJB2, respectively. Three PAPASH and three PASH/SAPHO overlapping patients who had also joint inflammation showed two different variants in NCSTN, one in WDR1 and PSTPIP1, and two variants in NLRC4, one of whom was present in a patient with a mixed phenotype characterized by gut and joint inflammation.
Limitations: Limited number of patients that can be counterbalanced by the rarity of syndromic HS.
Conclusion: Syndromic HS can be considered as a polygenic autoinflammatory condition; currently WES is a diagnostic tool allowing more accurate genotype-phenotype correlation.
Keywords: Acne; Arthritis; Autoinflammation; Gut inflammation; Hidradenitis suppurativa; Keratinization; Pyoderma gangrenosum; Whole-exome sequencing.
© 2022 S. Karger AG, Basel.