Division of Child and Adolescent Psychiatry, University of Cape Town, 46 Sawkins Road, Rondebosch, Cape Town, 7700, South Africa.
Research and Clinical Institute of Pediatrics, Pirogov Russian National Research Medical University, Moscow, Russian Federation.
Orphanet J Rare Dis. 2018 Sep 10;13(1):157. doi: 10.1186/s13023-018-0901-8.
Most evidence for TSC-associated neuropsychiatric disorders (TAND) to date have come from small studies and case reports, and very little is known about TAND in adults. We explored baseline TAND data from the large-scale international TOSCA natural history study to compare childhood and adult patterns, describe age-based patterns, and explore genotype-TAND correlations.
The study enrolled 2216 eligible participants with TSC from 170 sites across 31 countries at the data cut-off for the third interim analysis (data cut-off date: September 30, 2015). The most common behavioural problems (reported in > 10% of participants) were overactivity, sleep difficulties, impulsivity, anxiety, mood swings, severe aggression, depressed mood, self-injury, and obsessions. Psychiatric disorders included autism spectrum disorder (ASD, 21.1%), attention deficit hyperactivity disorder (ADHD, 19.1%), anxiety disorder (9.7%), and depressive disorder (6.1%). Intelligence quotient (IQ) scores were available for 885 participants. Of these, 44.4% had normal IQ, while mild, moderate, severe, and profound degrees of intellectual disability (ID) were observed in 28.1, 15.1, 9.3, and 3.1%, respectively. Academic difficulties were identified in 58.6% of participants, and neuropsychological deficits (performance <5th percentile) in 55.7%. Significantly higher rates of overactivity and impulsivity were observed in children and higher rates of anxiety, depressed mood, mood swings, obsessions, psychosis and hallucinations were observed in adults. Genotype-TAND correlations showed a higher frequency of self-injury, ASD, academic difficulties and neuropsychological deficits in TSC2. Those with no mutations identified (NMI) showed a mixed pattern of TAND manifestations. Children and those with TSC2 had significantly higher rates of intellectual disability, suggesting that age and genotype comparisons should be interpreted with caution.
These results emphasize the magnitude of TAND in TSC and the importance of evaluating for neuropsychiatric comorbidity in all children and adults with TSC, across TSC1 and TSC2 genotypes, as well as in those with no mutations identified. However, the high rates of unreported or missing TAND data in this study underline the fact that, even in expert centres, TAND remains underdiagnosed and potentially undertreated.
迄今为止，大多数与结节性硬化症相关的神经精神障碍（TAND）的证据都来自小型研究和病例报告，对成人 TAND 的了解甚少。我们探索了大规模国际 TOSCA 自然史研究中的基线 TAND 数据，以比较儿童和成人模式，描述基于年龄的模式，并探索基因型-TAND 相关性。
该研究在数据第三次中期分析截止日期（数据截止日期：2015 年 9 月 30 日）前，从 31 个国家的 170 个地点招募了 2216 名符合条件的 TSC 参与者。最常见的行为问题（报告率> 10%的参与者）为多动、睡眠困难、冲动、焦虑、情绪波动、严重攻击行为、情绪低落、自残和强迫症。精神疾病包括自闭症谱系障碍（ASD，21.1%）、注意力缺陷多动障碍（ADHD，19.1%）、焦虑症（9.7%）和抑郁症（6.1%）。共有 885 名参与者的智商（IQ）评分可用。其中，44.4%的人智商正常，而 28.1%、15.1%、9.3%和 3.1%的人分别有轻度、中度、重度和极重度智力障碍（ID）。58.6%的参与者存在学习困难，55.7%的参与者存在神经心理学缺陷（表现低于第 5 个百分位数）。儿童多动和冲动发生率较高，成人焦虑、情绪低落、情绪波动、强迫症、精神病和幻觉发生率较高。基因型-TAND 相关性显示 TSC2 中自残、ASD、学习困难和神经心理学缺陷的发生率更高。未发现突变（NMI）的人表现出混合的 TAND 表现模式。儿童和 TSC2 患者的智力障碍发生率明显较高，这表明在 TSC1 和 TSC2 基因型以及未发现突变的患者中，年龄和基因型的比较应谨慎解释。
这些结果强调了 TAND 在 TSC 中的严重程度，以及在所有 TSC 儿童和成人中评估神经精神合并症的重要性，包括 TSC1 和 TSC2 基因型以及未发现突变的患者。然而，在这项研究中，大量的 TAND 数据未被报告或缺失，这强调了即使在专家中心，TAND 仍然未被诊断和潜在治疗不足的事实。
