カーニー複合

BACKGROUND: Cardiac myxomas are the most common primary cardiac tumors and are usually solitary and sporadic. The presence of multiple synchronous lesions should raise suspicion for an underlying syndromic condition such as Carney complex (CNC). CASE SUMMARY: A 39-year-old asymptomatic man underwent transthoracic echocardiography for recurrent ventricular extrasystoles on electrocardiogram, which incidentally revealed multiple intracardiac masses. Multimodality imaging, including transesophageal echocardiography, computed tomography, and cardiac magnetic resonance, identified 4 distinct, highly mobile lesions involving the left ventricle, the mitro-aortic curtain, and left atrium, with features suggestive of myxomas. Given the high embolic risk, surgical excision was performed with concomitant mitral valve repair. Histopathological analysis confirmed cardiac myxomas, whereas immunohistochemistry showed reduced protein kinase A regulatory subunit 1-alpha expression. Genetic testing subsequently identified a protein kinase A regulatory subunit 1-alpha autosomal mutation, establishing the diagnosis of CNC. DISCUSSION: This case underscores the importance of multimodality imaging for accurate diagnosis and surgical planning. The detection of multiple synchronous cardiac masses should prompt genetic evaluation and long-term surveillance for CNC in clinical practice, because this syndrome may lead to endocrinological diseases such as Cushing syndrome and malignant endocrine tumors.

Rare pathogenic variants affecting components of the evolutionary conserved cAMP/protein kinase A (PKA) signalling pathway are implicated in a spectrum of adrenocortical disorders. Germline inactivating PRKAR1A variants leading to constitutive PKA activation, underlie primary pigmented nodular adrenocortical disease (PPNAD) in Carney complex. More recently, several patients with PPNAD and other types of bilateral nodular adrenal disease (BNAD) have been diagnosed with rearrangements in chromosome 19 at band p13.12, resulting in copy number gains of the entire PRKACA gene. Here, we report the identification of a 19p13.12 rearrangement, resulting in a duplication of the PRKACA gene, in a 32-year-old female from whom the genetic aetiology remained unknown for 20 years. Furthermore, we provide an updated overview of patients with PRKACA germline copy number gains that have previously been reported in the literature.

Background/Objectives: Post-Traumatic Stress Disorder (PTSD) is a complex psychiatric condition with a strong polygenic and stress-related biological basis. Although Genome-Wide Association Studies (GWAS) have acknowledged abundant risk variants, translating these findings into biologically meaningful candidates remains challenging. This study introduces an integrative computational approach from raw file preparation by python-coded application into downstream in-depth silico analyses designed to systematically refine GWAS signals for PTSD using fine-mapping, linkage disequilibrium (LD), and haplotype analyses. Methods: GWAS source file for PTSD was obtained from the GWAS Catalog (EFO_0001358) and analyzed using a custom Python pipeline integrating data harmonization, genome-wide visualization, LD estimation via 1000 Genomes reference panels, approximate Bayesian fine-mapping, and Haploview-inspired haplotype inference. SNPs were filtered based on statistical significance, LD structure, and posterior inclusion probability. Downstream systems' biology analyses included protein-protein interaction modeling and pharmacogenomics (PGx) annotations. Results: From the primary GWAS dataset, 100 top-ranked SNPs were selected, leading to the identification of 58 significant loci. LD and haplotype analyses refined these signals to 93 candidate SNPs (66 genes). Following the exclusion of non-protein-coding genes, 45 genes remained, and network-based prioritization generated a final list of 20 biologically connected and pharmacogenetically relevant genes associated with PTSD. Conclusions: This integrative approach provided a robust and reproducible framework for GWAS fine-mapping and variant prioritization, effectively reducing large-scale GWAS outputs to biologically interpretable PTSD risk loci and genes.

Heritable thyroid tumors represent a clinically important subset of endocrine neoplasms, accounting for approximately 3-9% of well-differentiated thyroid cancers and 25% of medullary thyroid cancers. In patients presenting with a new thyroid malignancy, recognition of an underlying hereditary cancer predisposition syndrome has important implications for management, surveillance for associated malignancies, and testing of at-risk relatives. This review summarizes the epidemiology, clinical presentation, histopathologic features, management, and surveillance recommendations for hereditary thyroid tumors in the setting of familial non-medullary thyroid cancer, multiple endocrine neoplasia type 2, familial adenomatous polyposis, Cowden syndrome, Li-Fraumeni syndrome, DICER1 syndrome, CHEK2-related cancer predisposition, and Carney complex. In the future, continued research is needed to better understand genotype-phenotype correlations, optimize surveillance strategies, and improve risk stratification to enable more personalized care for patients and families affected by these conditions.