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Neurodevelopmental assessments of rare genetic conditions
Developmental Medicine & Child Neurology ( IF 3.8 ) Pub Date : 2020-01-10 , DOI: 10.1111/dmcn.14451
Srinivas Gada 1
Affiliation  

With advances in genetic testing such as exome sequencing, there has been a welcome upsurge in the identification of new neurodevelopmental conditions. The study by Lane et al. on the cognitive and behavioural phenotype of Tatton-Brown-Rahman syndrome (TBRS), also known as DNMT3A overgrowth syndrome, adds to the growing body of conditions causing congenital overgrowth disorder with intellectual disability (OGID). Beckwith-Wiedemann, Sotos, and Weaver syndromes continue to remain the more common OGID syndromes. There are several challenges in carrying out neurodevelopmental assessments of rare conditions across a wide age range. These include choosing the most appropriate developmental test or battery of tests, required psychometric properties, and method of administration. Most of these tests are standardized with typically developing children of a certain age range, using particular methodology. Thus, the challenge in generalizability and usability of these tests on individuals with intellectual disability, such as TBRS. Therefore, the Wechsler Intelligence Scale for Children (WISC) and/or Wechsler Adult Intelligence Scale would have been a better choice of test, rather than the British Ability Scales, Third Edition (BAS3), to assess intelligence and ability across the age range studied. The BAS3 yields a general conceptual ability, which is similar but not identical to the full-scale IQ of the WISC. Likewise, the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) is not validated for use in individuals with moderate to severe learning disability. Moreover, it is possible to receive an ADOS classification of autism or autism spectrum disorder (ASD) and still not meet the clinical criteria for ASD in DSM-5. Furthermore, there is even more diagnostic uncertainty and overlap of ASD in individuals with severe intellectual disability. Hence the ADOS-2 should have been used with another tool such as the Autism Diagnostic Interview, Revised. Epidemiologically, the prevalence of intellectual disability without ASD has either remained stable or slightly decreased, but the incidence and prevalence of ASD has soared. This is glaringly highlighted in the study from Metropolitan Atlanta (US) showing a 269% increase in prevalence of overall ASD between 1991 to 2010. As in the TBRS study, could some of this rise be secondary to diagnostic substitution? Getting informed consent for participants over 18 years of age with moderate to severe intellectual disability also poses a challenge. Lastly, ADOS-2 and BAS3 were administered in a single session. This is cognitively exhausting for both typically developing children and those with intellectual disability. On the other hand, without a diagnostic label such as ASD, it will be impossible for our clients to access support, services, and resources, providing an additional predicament for professionals. Often one finds adaptive functioning to be proportionate to intellectual ability, which again corresponds to the severity of ASD. This was underscored by Lane et al. in their study. Developments in neurosciences have shown that neither learning nor adaptive functioning is a fixed state. Hence it is unsurprising to note that all the adults scored in the non-spectrum range on ADOS-2. In my opinion, such expression and/or evidence of neuroplasticity should prompt us to do the following. First, to give hope to patients and their carers. Next, to look beyond measurement of function. Then, to promote habilitation along the International Classification of Functioning, Disability and Health model, using the six ‘F-words’ of neurodisability: Family, Friends, Function, Fun, Fitness, and Future. Last, the finding of an uneven cognitive profile (such as in TBRS) should prompt us to build on the individuals’ strengths, interests, and opportunities available. To sum up, accurate diagnosis and description of these newer syndromes would help in genetic counselling, planning health surveillance (such as for cancer), giving a prognosis, and ultimately offering us newer insights.

中文翻译:

罕见遗传病的神经发育评估

随着基因检测(如外显子组测序)的进步,新的神经发育疾病的识别出现了可喜的热潮。Lane 等人的研究。对 Tatton-Brown-Rahman 综合征 (TBRS)(也称为 DNMT3A 过度生长综合征)的认知和行为表型的研究增加了导致先天性过度生长障碍伴智力障碍 (OGID) 的疾病不断增多。Beckwith-Wiedemann、Sotos 和 Weaver 综合征仍然是更常见的 OGID 综合征。在对广泛年龄范围内的罕见疾病进行神经发育评估时,存在一些挑战。这些包括选择最合适的发展测试或测试组合、所需的心理测量特性和管理方法。大多数这些测试都是针对特定年龄范围的典型发育儿童使用特定方法进行标准化的。因此,这些测试对智障人士(如 TBRS)的普遍性和可用性存在挑战。因此,Wechsler 儿童智力量表 (WISC) 和/或 Wechsler 成人智力量表将是更好的测试选择,而不是英国能力量表第三版 (BAS3),以评估所研究年龄段的智力和能力. BAS3 产生一般概念能力,与 WISC 的全面智商相似但不完全相同。同样,自闭症诊断观察计划第二版 (ADOS-2) 未验证可用于具有中度至重度学习障碍的个人。而且,有可能接受 ADOS 自闭症或自闭症谱系障碍 (ASD) 分类,但仍不符合 DSM-5 中 ASD 的临床标准。此外,在严重智力障碍的个体中,ASD 的诊断不确定性和重叠甚至更多。因此,ADOS-2 应该与其他工具一起使用,例如自闭症诊断访谈,修订版。从流行病学上看,没有 ASD 的智障患病率要么保持稳定,要么略有下降,但 ASD 的发病率和患病率却在飙升。这在亚特兰大大都会(美国)的研究中得到了明显的强调,表明 1991 年至 2010 年间 ASD 的总体患病率增加了 269%。与 TBRS 研究一样,这种上升中的一些可能是诊断替代的次要原因吗?获得 18 岁以上患有中度至重度智力障碍的参与者的知情同意也带来了挑战。最后,ADOS-2 和 BAS3 是在一个会话中管理的。对于正常发育的儿童和智障儿童来说,这在认知上都令人筋疲力尽。另一方面,如果没有 ASD 等诊断标签,我们的客户将无法获得支持、服务和资源,为专业人士提供了额外的困境。通常人们会发现适应性功能与智力成正比,这又与 ASD 的严重程度相对应。Lane 等人强调了这一点。在他们的研究中。神经科学的发展表明,学习和适应性功能都不是固定状态。因此,注意到所有成年人在 ADOS-2 的非频谱范围内得分也就不足为奇了。在我看来,这种神经可塑性的表达和/或证据应该促使我们做以下事情。首先,给患者和他们的照顾者带来希望。接下来,超越功能的测量。然后,使用神经功能障碍的六个“F 字”:家庭、朋友、功能、乐趣、健身和未来,按照国际功能、残疾和健康分类模型促进康复。最后,发现不均衡的认知特征(例如在 TBRS 中)应该促使我们建立在个人优势、兴趣和可用机会的基础上。总而言之,准确诊断和描述这些较新的综合征将有助于遗传咨询、规划健康监测(例如癌症)、提供预后、
更新日期:2020-01-10
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