Autism spectrum disorder in tuberous sclerosis complex: searching for risk markers.

Maria Paola Canevini,Katherine Turner,Giulia Federica Scornavacca,Elisabetta Magnaghi,Monica Saccani,Aglaia Vignoli,Francesca La Briola,Chiara Vannicola,Angela Peron

doi:10.1186/s13023-015-0371-1

Maria Paola Canevini, Katherine Turner + Show 7 more

Open Access

https://doi.org/10.1186/s13023-015-0371-1

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Abstract

BackgroundNeuropsychiatric disorders are present in up to 90 % of patients with Tuberous Sclerosis Complex (TSC), and represent an important issue for families. Autism Spectrum Disorder (ASD) is the most common neurobehavioral disease, affecting up to 61 % of patients. The aims of this study were: 1) to assess the prevalence of ASD in a TSC population; 2) to describe the severity of ASD; 3) to identify potential risk factors associated with the development of ASD in TSC patients.MethodsWe selected 42 individuals over age 4 years with a definite diagnosis of TSC and followed at a TSC clinic in Northern Italy. We collected and reported clinical and genetic data, as well as cognitive level, for each of them. We administered the Social Communication Questionnaire (SCQ) as a reliable screening tool for ASD, and performed comparisons between the average scores and each clinical and genetic feature.ResultsSeventeen out of 42 patients (40.5 %) had a score at the SCQ suggestive of ASD (≥15 points). When calculated for each cognitive level category, the average SCQ score tended to be progressively higher in patients with a worse cognitive level, and the number of pathological SCQ scores increased with worsening of intellectual disability. With respect to ASD severity, the scores were equally distributed, indicating that the degree of ASD in TSC patients may have a large variability. By comparing the average SCQ scores with the clinical features, we found statistically significant correlations with epilepsy, seizure onset before age one year, spasms, mutations in TSC2, cognitive level, sleep disorders, and other psychiatric problems, but not with seizure frequency, tubers localization and gender.ConclusionsOur study showed a prevalence of ASD of 40.5 %, confirming the higher risk for this disorder in patients with TSC. However, the severity seems to have a notable variability in TSC patients. Risk factors for ASD are epilepsy, infantile spams, and mutations in TSC2.

Highlights

Neuropsychiatric disorders are present in up to 90 % of patients with Tuberous Sclerosis Complex (TSC), and represent an important issue for families
The localization of cortical tubers was identified as another risk factor for developing autism spectrum disorder (ASD) in TSC patients: both frontal and temporal tubers were associated with ASD, and cyst-like cortical tubers were more common in patients with TSC and ASD [8]
When calculated for each cognitive level category, the average Social Communication Questionnaire (SCQ) score tended to be progressively higher in patients with a worse cognitive level: 9.8 (±6.7) in patients with mild intellectual disability (ID), 11.75 (±8.1) in patients with moderate ID, and 17.7 (±6.2) in patients with severe ID (Fig. 3a)

Summary

Introduction

Neuropsychiatric disorders are present in up to 90 % of patients with Tuberous Sclerosis Complex (TSC), and represent an important issue for families. Autism Spectrum Disorder (ASD) is the most common neurobehavioral disease, affecting up to 61 % of patients. The aims of this study were: 1) to assess the prevalence of ASD in a TSC population; 2) to describe the severity of ASD; 3) to identify potential risk factors associated with the development of ASD in TSC patients. Among the psychiatric problems associated with TSC, autism spectrum disorder (ASD) is the most common, affecting up to 61 % of patients [3]. Epilepsy is one of the major issues in TSC [4] and is considered a potential risk factor for ASD in TSC patients, especially when epilepsy starts early and with infantile spasms. Correlations between ASD and genotype are emerging, and TSC2 mutations seem to be more frequently associated with ASD, regardless the mutation type [8]

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