Cabal-Herrera Ana María, Saldarriaga-Gil Wilmar, Salcedo-Arellano Maria Jimena, Hagerman Randi J
Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis Health, Sacramento, CA, USA.
School of Medicine, Universidad del Valle, Cali, Colombia.
Intractable Rare Dis Res. 2020 May;9(2):113-118. doi: 10.5582/irdr.2020.01028.
Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and autism spectrum disorder. In most cases, it is due to an expansion of the CGG triplet to more than 200 repeats within the promoter region of the gene. In the premutation (PM) the trinucleotide is expanded to 55-200 repeats. PM carriers can present with disorders associated with the PM including fragile X-associated tremor/ataxia syndrome (FXTAS) and fragile X-associated ovarian insufficiency (FXPOI). Recently fragile X-associated neuropsychiatric disorders (FXAND) was proposed as an umbrella term to include the neuropsychiatric disorders that are more prevalent in PM carriers compared to the general population such as anxiety, depression, chronic fatigue, alcohol abuse, and psychosis, among others. The patient in our study was evaluated by a team of clinicians from the University del Valle in Cali who traveled to Ricaurte, a Colombian town known for being a genetic geographic cluster of FXS. A detailed medical history was collected and complete physical, neurological and psychiatric evaluations were performed in addition to molecular and neuroradiological studies. We report the case of a 78-year-old man, PM carrier, without FXTAS whose main clinical presentation consists of behavioral changes and psychosis. Brain imaging revealed white matter lesions in the periventricular region and mild cerebral atrophy. Although anxiety and depression are the most common neuropsychiatric manifestations in PM carriers, it is important to perform a complete psychiatric evaluation since some patients may present with behavioral changes and psychosis.
脆性X综合征（FXS）是智力残疾和自闭症谱系障碍最常见的遗传性病因。在大多数情况下，它是由于基因启动子区域内的CGG三联体扩展至200多个重复序列。在前突变（PM）中，三核苷酸扩展至55 - 200个重复序列。PM携带者可能会出现与PM相关的疾病，包括脆性X相关震颤/共济失调综合征（FXTAS）和脆性X相关卵巢功能不全（FXPOI）。最近，脆性X相关神经精神疾病（FXAND）被提议作为一个统称，用于涵盖与普通人群相比在PM携带者中更普遍的神经精神疾病，如焦虑、抑郁、慢性疲劳、酒精滥用和精神病等。我们研究中的患者由来自卡利的瓦尔大学的一组临床医生进行评估，他们前往里考尔特，这是哥伦比亚一个以FXS遗传地理聚集区而闻名的城镇。除了分子和神经放射学研究外，还收集了详细的病史并进行了全面的身体、神经和精神评估。我们报告了一例78岁男性PM携带者的病例，该患者无FXTAS，其主要临床表现为行为改变和精神病。脑成像显示脑室周围区域有白质病变和轻度脑萎缩。虽然焦虑和抑郁是PM携带者最常见的神经精神表现，但进行全面的精神评估很重要，因为一些患者可能会出现行为改变和精神病。
