Liver findings in patients with Carney complex, germline PRKAR1A pathogenic variants, and link to cardiac myxomas. Issue 6 (June 2020)

• Record Type: Journal Article
• Authors: Tirosh, Amit; Hamimi, Ahmed; Faucz, Fabio; Aharon-Hananel, Genya; Zavras, Phaedon D; Bonella, Belen; Auerbach, Adi; Gillis, David; Lyssikatos, Charalampos; Belyavskaya, Elena; Stratakis, Constantine A; Gharib, Ahmed M
• Is Part Of: Endocrine-related cancer. Volume 27:Issue 6(2020)
• Page Start: 355
• Page End: 360
• Publication Date: 2020-06
• Subjects: Carney complex -- genotype–phenotype -- PRKAR1A -- liver; Endocrine glands -- Cancer -- Periodicals; Endocrinology -- Periodicals; Cancer -- Endocrine aspects -- Periodicals; 616.9944005
• DOI: 10.1530/ERC-19-0517
• Languages: English
• ISSNs: 1351-0088

Abstract

Abstract : This study aimed to evaluate liver involvement in patients with Carney complex (CNC) based on a large cohort and to analyze any germline PRKAR1A genotype–phenotype association of liver disease. The study included 83 patients with CNC, followed between 1995 and 2018 at a tertiary research center. We reviewed liver images, recorded types and number of lesions and analyzed per genotype: all patients were sequenced for the PRKAR1A gene. A total of 29/83 patients (24.0%) had liver radiological findings. Patients with liver lesion had a significantly higher rate of pathogenic variants detected in the PRKAR1A gene (72.4 vs 38.9%, P = 0.005, respectively). Patients with a pathogenic variant detected on germline PRKAR1A analysis had a higher risk for having a liver lesion compared with patients with wild-type (WT) PRKAR1A alleles (21/42 (50.0%) vs 8/41 (19.5%), respectively, P = 0.004). Among patients with liver lesions, those with a nonsense PRKAR1A pathogenic-variant had more liver lesions (7/7) than among those with other pathogenic-variant types (8/22, P = 0.001). In multivariable analysis, detection of liver lesion(s) was associated with an odds ratio of 5.2 for cardiac myxomas (95% CI 1.55–17.49, P = 0.008). In conclusion, patients with CNC, particularly with a PRKAR1A pathogenic variant, have a higher rate of liver lesions. Additionally, liver lesions are associated with a high risk for cardiac myxomas in this population.