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This is a Case Report study (also classified as: Literature Review).

May 6, 2026SHILAP Revista de lepidopterología0 citationsOpen Access

Case Report: Thymoma-associated stiff person syndrome and myasthenia gravis: an index case with exploratory exome sequencing and review of reported cases

LZLu ZhaoJilin University LFLinan FangJilin University MTMingbo TangJilin University

Key Points

This report aims to highlight a rare case of thymoma-associated stiff person syndrome and myasthenia gravis, focusing on diagnostic challenges and genomic insights.
Detailed clinical evaluations and investigations
Exploratory whole-exome sequencing on thymoma tissue
Pathway analysis of genomic data
Literature review of additional reported cases
Index patient showed substantial improvement post-treatment with immunotherapy and thymectomy
Identified somatic variants in thymoma including immune-signaling genes
Thymoma associated with GAD65 positivity and mixed histology in reviewed cases

Abstract

Background Thymoma is frequently associated with myasthenia gravis (MG), but the coexisting of stiff person syndrome (SPS) is exceedingly rare. This overlap syndrome poses diagnostic and therapeutic challenges, and its immunopathogenic basis is not well understood. Methods A 55-year-old woman with thymoma-associated SPS and MG was evaluated using detailed clinical, electrophysiological, serological and radiologic investigations. In addition, a PubMed-based literature review of published cases of thymoma complicated by SPS with MG was conducted. Exploratory whole-exome sequencing (WES) with pathway analysis were performed on resected thymoma tissue. Results The index patient presented with progressive gait unsteadiness, painful axial and lower-limb stiffness, dysarthria and dysphagia. Examination revealed marked truncal rigidity and exaggerated startle responses. Serology demonstrated high-titer anti–glutamic acid decarboxylase 65 (GAD65) and elevated acetylcholine receptor (AChR) antibodies. Chest computed tomography (CT) demonstrated an anterior mediastinal soft-tissue mass highly suggestive of thymoma. Treatment with immunotherapy, symptomatic agents and thymectomy resulted in substantial clinical improvement. The literature search identified seven additional patients with thymoma-associated SPS and MG, typically characterized by GAD65 positivity, World Health Organization (WHO) B1/B2 mixed histology, and favorable outcomes after combined immunotherapy and surgical resection. WES of the thymoma revealed a somatic CACNA1A frameshift variant and variants in immune-signaling genes, with enrichment of pathways related to calcium channels, γ-aminobutyric acidergic (GABAergic) synapses and immune regulation. Conclusion Thymoma-associated SPS and MG constitute a rare but recognizable overlap syndrome. Integration of clinical, literature and exploratory genomic data supports a convergent mechanism involving thymic epithelial neoplasia, impaired inhibitory neurotransmission and neuromuscular junction autoimmunity.

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