Seminoma Caused by PDE11A Frameshift Variant with Multiple Abnormalities: A Case Report

INTRODUCTION: Testicular germ cell tumor is a rare malignant tumor predominantly affecting young males. In addition to well-established risk factors like cryptorchidism, genetic factors are increasingly recognized as significant contributors. This case report highlights a patient diagnosed with seminoma associated with multiple abnormalities and explores the genetic basis behind these manifestations. CASE PRESENTATION: A 22-year-old East Asian male presented with left-sided varicocele and recent onset testicular pain. Clinical examination and imaging revealed a smaller left testicle and a testicular nodule. Surgical excision and subsequent histopathology confirmed seminoma and germ cell neoplasia in situ. Additional medical investigations identified brain dysplasia, social interaction challenges, learning impairments, and a presacral mass suggestive of teratoma. Genetic analysis using exome sequencing detected a frameshift variant in the PDE11A gene, predicted by AlphaFold3 to significantly disrupt protein structure and function. The patient later underwent orchiectomy following recurrence confirmation. CONCLUSION: This report emphasizes the potential pathogenic role of the PDE11A frameshift variant in seminoma development and associated systemic abnormalities. The application of advanced computational tools like AlphaFold3 can provide deeper molecular insights into genetic variants and further elucidate their clinical implications.