Tuberous sclerosis complex — MRCPsych Paper A MCQ

Correct answer: A — Autosomal dominant pathogenic variant in TSC1 or TSC2

The correct answer is A. The combination of cortical tubers, multiple facial angiofibromas, epilepsy and autism spectrum disorder is characteristic of tuberous sclerosis complex. It results from a heterozygous loss-of-function pathogenic variant in the tumour-suppressor gene TSC1 or TSC2 and has autosomal dominant inheritance, although many affected children have a de novo variant. An FMR1 expansion can cause autism and intellectual disability but not cortical tubers or angiofibromas. PAH deficiency causes phenylketonuria, while mitochondrial variants may cause epilepsy and neurodevelopmental impairment without these characteristic hamartomatous lesions. Paternal uniparental disomy of chromosome 15 is a mechanism of Angelman syndrome and does not explain the cutaneous and MRI findings.

Reference: NHS England National Genomics Education Programme. GeNotes Knowledge Hub: Tuberous sclerosis complex, sections ‘Genomics’ and ‘Inheritance and genomic counselling’. Last reviewed 11 March 2025. https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/tuberous-sclerosis-complex/