Probable Genetic Association Between Lhermitte-Duclos Disease/Cowden Syndrome and Autism Spectrum Disorder: A Case Report and Literature Comprehension

Background: Lhermitte-Duclos disease (LDD), known as dysplastic cerebellar gangliocytoma, is a hamartomatous lesion that causes progressive mass effect in the posterior fossa. Cowden syndrome (CS) is a rare autosomal dominant disorder characterized by an increased risk of developing various systemic malignancies. Both conditions result from mutations in the PTEN gene, which disrupts normal cell growth and proliferation. Some children with PTEN mutations may present with developmental delay or autism spectrum disorder (ASD), potentially associated with CS. Methods: Herein, we present a rare case involving a mother with LDD/CS and her child with ASD. We discuss recommendations for screening and management of LDD/CS patients and PTEN-related ASD and provide a brief literature review. Comprehensive clinical evaluation, diagnostic imaging, and genetic analysis were performed on a female patient with LDD/CS, who underwent surgical treatment and was followed up for 10 years. Genetic testing was also conducted on her 10-year-old child, diagnosed with ASD. Results: The LDD/CS patient underwent successful partial surgical resection of the dysplastic cerebellar gangliocytoma and achieved full neurological recovery. Ten-year follow-up showed no evidence of tumor recurrence. Genetic testing in both the mother and the child confirmed PTEN gene mutations. Conclusions: This case supports a probable association between an LDD/CS-affected parent and an ASD-affected child, linked to PTEN mutations inherited in an autosomal dominant manner. Given the significant risk of malignancy and neurodevelopmental disorders associated with PTEN mutations, patients suspected of having LDD/CS and children with ASD should undergo regular screening for PTEN-related neoplasms and receive appropriate genetic counseling.