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Review
. 2025 Jun;46(6):2571-2580.
doi: 10.1007/s10072-025-08065-2. Epub 2025 Feb 25.

The clinical interface of tuberous sclerosis complex and autism spectrum disorder: insights and future directions

Reet Ramani  1 , Barika Fatima  1 , Abuzar Hussain  1 , Umer Shahid  1 , Aman Kamani  1 , Sahibzada Mohammad Abu Bakar  1 , Hufsa Naveed  2 , Tooba Naveed  1 , Saba Ambreen Aftab  1 , Ahmed Zubair Abbasi  1
Affiliations
Review

The clinical interface of tuberous sclerosis complex and autism spectrum disorder: insights and future directions

Reet Ramani et al. Neurol Sci. 2025 Jun.

Abstract

Background and objective: Tuberous sclerosis complex (TSC) is a hereditary disorder that leads to tumor growth in various organs. Manifestations from mutations in the TSC1 or TSC2 genes comprise seizures, developmental delay, and skin abnormalities. This literature search has been dedicated to emphasizing the critical role of early diagnosis and the formulation of individualized plans for this target population with co-occurring TSC and Autism Spectrum Disorder (ASD).

Experimental procedure: Behavioral and developmental tests can evaluate ASD symptoms; neuroimaging methods like functional MRI and PET scans can identify brain abnormalities, and molecular genetic analysis can detect TSC1/TSC2 mutations. Differential Diagnostic Approach These include medical histories and physical examinations to consider that ASD and TSC present the same symptoms.

Results: Although 90% of TSC patients are reported to have TSC-associated neuropsychiatric disorders, 30-50% of patients fulfil the clinical criteria of ASD. In comparison, the estimate for the rate of ASD prevalence in TSC patients ranges from 17 to 63%, with the characteristics of infantile spasms and early-onset epilepsy. The diagnosis is further challenged by the fact that there are shared symptoms between both, namely seizures and intellectual impairment.

Conclusion: The shared symptoms between TSC and ASD suggest the need for multidisciplinary approaches in both diagnosis and treatment. A personalized therapeutic plan should include behavioral therapy, medication with Everolimus, mammalian target of rapamycin (mTOR) inhibitors, and advanced neuroimaging. The future of research in biomarkers, molecular medicines, and improving diagnostic protocols holds great promise for optimizing patient care and treatment options.

Keywords: Autism spectrum disorder; TSC1/TSC2; Tuberous sclerosis complex; Tuberous sclerosis complex-associated neuropsychiatric disorders.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare that they have no conflict of interest. Ethics approval: Not applicable for study.

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