BACKGROUND Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disorder, typically presenting with hypertension, hematuria, or progressive renal dysfunction. However, it can have a broad range of initial presentations and, in uncommon cases, may mimic other abdominal disorders. This report presents a case of ADPKD manifesting as an epigastric mass in a patient without a family history, highlighting its importance in the differential diagnosis of upper abdominal masses. CASE REPORT A 62-year-old woman presented to our primary care clinic with a 5-day history of a painless epigastric mass and right hypochondriac pain. She had hypertension and dyslipidemia, without a known family history of ADPKD. On examination, a firm mass was palpable in the epigastrium, accompanied by hepatomegaly. Laboratory investigations revealed mild renal insufficiency, microscopic hematuria, and proteinuria. The patient underwent abdominal ultrasonography and contrast-enhanced computed tomography, which demonstrated multiple cysts in both kidneys and the liver, consistent with ADPKD. She was evaluated by the hepatobiliary surgery team, who recommended symptomatic management. She was also assessed by the nephrology team; further evaluation for associated complications, including mitral valve prolapse and intracranial aneurysms, yielded normal findings. She continues regular follow-up with the primary care and nephrology teams for blood pressure optimization and renal function monitoring. CONCLUSIONS This case highlights the need to consider ADPKD in patients who present with upper abdominal masses. Early imaging and a multidisciplinary evaluation are essential for establishing an accurate diagnosis and ensuring appropriate management, particularly in patients without a clear family history.

Congenital anomalies often arise during critical developmental time windows, yet the underlying mechanisms remain unclear. Here, we identify a time-specific FGFR2-retinoic acid signaling axis regulating postnatal coronal suture development through dura mater-suture mesenchyme interactions. FGFR2 signaling gradually declines after birth, leading to reduced retinoic acid signaling by moderating the expression of Aldh1a3 in the dura mater and suture mesenchyme alongside that of Rbp1 in the dura mater, thereby preserving GLI1+ progenitors and restraining osteogenesis to maintain suture patency. Importantly, FGFR2 overactivation in Fgfr2IIIc mutant mice within an early time window, disrupts this physiological FGFR2-retinoic acid signaling decline by upregulating Rbp1 and Aldh1a3 through enhanced P38 signaling. This leads to increased retinoic acid synthesis, premature osteogenic differentiation of GLI1+ progenitors, and coronal suture craniosynostosis. Significantly, genetic restoration of retinoic acid signaling rescues craniosynostosis in Fgfr2IIIc mutant mice, confirming retinoic acid signaling as a key downstream effector of FGFR2 signaling. Notably, restoration of suture patency alone rescues neurocognitive dysfunctions in Fgfr2IIIc mutant mice despite Fgfr2 mutation in the brain, demonstrating that the neurocognitive impairments primarily arise from cranial structural constraints and elevated intracranial pressure rather than intrinsic neural defects. This critical postnatal time window in mice parallels the timing of FGFR2-related craniosynostosis onset in humans, underscoring the importance of this study in advancing our understanding of the molecular and cellular mechanisms in craniosynostosis. Our findings define a temporally regulated FGFR2-P38-retinoic acid signaling axis and highlight retinoic acid signaling as a promising therapeutic target in FGFR2 overactivation-related craniosynostosis.