Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Genes (Basel). 2021 Feb 27;12(3):351. doi: 10.3390/genes12030351.
: Activity dependent neuroprotective protein (ADNP) syndrome is one of the most common single-gene causes of autism spectrum disorder (ASD) and intellectual disability, however, the phenotypes remain poorly described. Here we examine the sensory reactivity phenotype in children and adolescents with ADNP syndrome. Twenty-two individuals with ADNP syndrome received comprehensive clinical evaluations including standardized observations, caregiver interviews, and questionnaires to assess sensory reactivity symptoms. Relationships between sensory symptoms and age, sex, ASD, IQ, and adaptive behavior were examined. Genotype-phenotype correlations with the recurrent p.Tyr719* variant were also explored. Sensory reactivity symptoms were observed and reported in all participants. A syndrome-specific phenotype was identified, characterized by high levels of sensory seeking across tactile, auditory, and visual domains. Tactile hyporeactivity, characterized by pain insensitivity, was reported in the majority of participants. Sensory symptoms were identified across individuals regardless of age, sex, IQ, adaptive ability, genetic variant, and most importantly, ASD status. No significant differences were identified between participants with and without the recurrent p.Tyr719* variant on any sensory measure. Sensory reactivity symptoms are a common clinical feature of ADNP syndrome. Quantifying sensory reactivity using existing standardized measures will enhance understanding of sensory reactivity in individuals with ADNP syndrome and will aid in clinical care. The sensory domain may also represent a promising target for treatment in clinical trials.
活性依赖型神经营养蛋白（ADNP）综合征是自闭症谱系障碍（ASD）和智力障碍最常见的单一基因病因之一，但表型仍描述不佳。在此，我们研究了 ADNP 综合征患儿和青少年的感觉反应表型。22 名 ADNP 综合征患者接受了全面的临床评估，包括标准化观察、照顾者访谈和问卷评估，以评估感觉反应症状。研究了感觉症状与年龄、性别、ASD、智商和适应行为之间的关系。还探讨了与复发性 p.Tyr719变异相关的基因型-表型相关性。所有参与者均观察到并报告了感觉反应症状。确定了一种综合征特异性表型，其特征是在触觉、听觉和视觉领域均存在高水平的感觉寻求。大多数参与者报告了触觉反应迟钝，表现为对疼痛不敏感。无论年龄、性别、智商、适应能力、遗传变异，尤其是 ASD 状态如何，个体之间都存在感觉症状。在任何感觉测量中，均未发现具有和不具有复发性 p.Tyr719变异的参与者之间存在显著差异。感觉反应症状是 ADNP 综合征的常见临床特征。使用现有的标准化测量来量化感觉反应，将有助于加深对 ADNP 综合征个体感觉反应的理解，并有助于临床护理。感觉域也可能成为临床试验中治疗的有前途的靶点。
