Comprehensive phenotyping of neuropsychiatric traits in a multiplex 3q29 deletion family: a case report
Comprehensive phenotyping of neuropsychiatric traits in a multiplex 3q29 deletion family: a case report
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DOI：
10.1186/s12888-020-02598-w
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发表时间：
2020-04-22
期刊：
影响因子：
4.4
通讯作者：
Mulle, Jennifer Gladys
中科院分区：
文献类型：
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作者：
Murphy, Melissa M.;Burrell, T. Lindsey;Mulle, Jennifer Gladys
背景3q29缺失综合征与一系列内科、神经发育和精神病学表型有关。这种缺失通常是从头开始的，但有报道称，这种缺失是从明显未受影响的父母那里遗传来的。这些未受影响或受轻度影响的个体的存在表明，3q29缺失综合征严重影响的病例可能存在确证偏差，因此可能高估了3q29缺失的更有害后果。然而，3q29缺失综合征发病率的很大一部分是由精神疾病引起的。在许多病例报告中，先证者和传播者父母没有被系统地评估精神特征。在这里，我们报告了一个多基因家族中所有3q29缺失携带者的神经发育和神经精神特征的系统表型方案的结果。通过埃默里大学3q29登记处的病例介绍，发现了一个多胎家系，其中三个后代具有父系遗传的3q29缺失。我们使用我们之前描述的标准化的、系统的表型分析方法评估了所有4个3q29缺失的家庭成员。传播者的父母没有报告精神病史，然而，经过评估，他被发现符合多项精神诊断标准，包括以前未诊断的分裂情感障碍。家系中所有四个3q29缺失的人都有多种精神疾病诊断，干扰了生活质量，并阻碍了成功的学术和职业功能。所有个体的认知能力均为平均水平或低于平均水平，但在正常范围内。结论这是首例遗传性3q29缺失综合征的病例报告，该家系中的所有受累个体均已使用由专家临床医生管理的标准仪器，对其神经发育和精神症状进行了全面和系统的评估。我们的调查显示，患有3q29缺失综合征的人可能患有令人衰弱的精神疾病，但只有通过专家的专门评估才能明显表现出来。在缺乏适当评估的情况下，3q29缺失综合征患者可能患有精神疾病，但缺乏获得护理的途径。这里评估的所有个体的认知能力都在正常范围内，每个人都有多项精神疾病诊断，这表明认知能力本身并不能代表3q29缺失相关残疾的代表性指标。这些结果需要在更大的3q29缺失综合征患者队列中复制。
Background 3q29 deletion syndrome is associated with a range of medical, neurodevelopmental, and psychiatric phenotypes. The deletion is usually de novo but cases have been reported where the deletion is inherited from apparently unaffected parents. The presence of these unaffected or mildly affected individuals suggests there may be an ascertainment bias for severely affected cases of 3q29 deletion syndrome, thus the more deleterious consequence of the 3q29 deletion may be overestimated. However, a substantial fraction of 3q29 deletion syndrome morbidity is due to psychiatric illness. In many case reports, probands and transmitting parents are not systematically evaluated for psychiatric traits. Here we report results from a systematic phenotyping protocol for neurodevelopmental and neuropsychiatric traits applied to all 3q29 deletion carriers in a multiplex family. Case presentation Through the 3q29 registry at Emory University, a multiplex family was identified where three offspring had a paternally inherited 3q29 deletion. We evaluated all 4 3q29 deletion family members using our previously described standardized, systematic phenotyping protocol. The transmitting parent reported no psychiatric history, however upon evaluation he was discovered to meet criteria for multiple psychiatric diagnoses including previously undiagnosed schizoaffective disorder. All four 3q29 deletion individuals in the pedigree had multiple psychiatric diagnoses that interfered with quality of life and prohibited successful academic and occupational functioning. Cognitive ability for all individuals was average or below average, but within the normal range. Conclusions This is the first case report of inherited 3q29 deletion syndrome where all affected individuals in the pedigree have been comprehensively and systematically evaluated for neurodevelopmental and psychiatric symptoms, using a standard battery of normed instruments administered by expert clinicians. Our investigation reveals that individuals with 3q29 deletion syndrome may have psychiatric morbidity that is debilitating, but only apparent through specialized evaluation by an expert. In the absence of appropriate evaluation, individuals with 3q29 deletion syndrome may suffer from psychiatric illness but lack avenues for access to care. The individuals evaluated here all have cognition in the normal range alongside multiple psychiatric diagnoses each, suggesting that cognitive ability alone is not a representative proxy for 3q29 deletion-associated disability. These results require replication in a larger cohort of individuals with 3q29 deletion syndrome.