Under-recognised neurocognitive deficits in adults and adolescents with tuberous sclerosis complex

Correspondence to Dr Mark R Keezer; [email protected]

WHAT IS ALREADY KNOWN ON THIS TOPIC

• Intellectual disability is present in many children with tuberous sclerosis complex (TSC).

WHAT THIS STUDY ADDS

• Objective tests of cognitive function are useful in identifying neurocognitive deficits in adults and adolescents with TSC, even among those without a known history of intellectual disability.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

• The results of this study will sensitise healthcare providers and patients to the presence of more subtle neurocognitive deficits in adults and adolescents with TSC.

• A clearer understanding of a person’s intellectual abilities allows for better planning of educational, social and clinical management strategies.

Introduction

Tuberous sclerosis complex (TSC) is a neurocutaneous genetic disease associated with the presence of hamartomas in the brain (eg, cortical tubers) and other vital organs, affecting one in 6000 live births.¹ Approximately 85% of individuals have an autosomal dominant pathogenic variant in the TSC1 or TSC2 genes.² People with TSC (PwTSC) often present with epilepsy, intellectual disability (ID) and autism spectrum disorder.¹ The severity of these disease manifestations vary widely between individuals, even between members of the same family.³ The diagnosis of TSC can be made at any age.⁴ Neurocognitive impairments are frequent among PwTSC, with deficits in working memory, cognitive flexibility and divided attention being particularly prevalent.⁵ Prior studies have reported a negative association between the cerebral tuber count and the IQ of individuals.^{6 7}

The TAND Checklist is recommended for screening PwTSC for behavioural and cognitive impairments.⁸ This checklist contains 12 sections, cataloguing patient-reported and physician-diagnosed neuropsychiatric and neurocognitive comorbidities.^{5 8} Many of these comorbidities, however, are often unrecognised by patients and under-diagnosed by physicians.^9–11 This is especially the case when these manifestations are mild or when a person is diagnosed with TSC only as an adult. PwTSC, especially adults and older adolescents, would benefit from standardised screening tools specific to their age.^{12 13} To better identify and address the neurocognitive impairments in PwTSC, administration of an objective and validated screening tool, to be used in conjunction with the TAND Checklist, could facilitate the planning of educational, social and clinical management strategies.^{12 13}

The first goal of our study was...