Casarelli Livia, Minnei Maurizio, Pitzianti Mariabernarda, Armando Marco, Pontillo Maria, Vicari Stefano, Pasini Augusto
aDepartment of System Medicine, Child Neurology and Psychiatry Unit, 'Tor Vergata' University of Rome bDepartment of Neuroscience, Unit of Child Neuropsychiatry, Children's Hospital Bambino Gesù, IRCCS, Rome, Italy.
Psychiatr Genet. 2016 Oct;26(5):187-92. doi: 10.1097/YPG.0000000000000144.
22q11 Deletion syndrome (22q11DS) is a neurogenetic disorder, resulting from a hemizygous microdeletion on the long arm of chromosome 22. In 22q11DS, the phenotypic expression is highly variable. Approximately one-third of all individuals with 22q11DS develop schizophrenia-like psychotic disorder. Among the genes in the deleted region, catechol-O-methyltransferase (COMT) has a particular relevance for psychiatric disorders: lower COMT enzymatic activity decreases the clearance of dopamine (DA), yielding higher levels of catecholamines in the central nervous system. Deficits in myelinogenesis and dysfunctions in the DA system could justify the white matter abnormalities in motor/premotor circuits described in 22q11DS. The alterations in DA could determine the high incidence of psychiatric disorders and the presence of neurological soft signs in 22q11DS. Neurological soft signs are defined as non-normative performance on an examination of motor and sensory tasks without focal neurological deficits. COMT haploinsufficiency, DA dysfunction, and white matter abnormalities may contribute toward the presence of neurological soft signs in 22q11DS.
22q11缺失综合征（22q11DS）是一种神经遗传性疾病，由22号染色体长臂上的半合子微缺失引起。在22q11DS中，表型表达高度可变。所有22q11DS患者中约有三分之一会发展为精神分裂症样精神病性障碍。在缺失区域的基因中，儿茶酚-O-甲基转移酶（COMT）与精神疾病特别相关：较低的COMT酶活性会降低多巴胺（DA）的清除率，导致中枢神经系统中儿茶酚胺水平升高。髓鞘形成缺陷和DA系统功能障碍可能是22q11DS中运动/运动前回路白质异常的原因。DA的改变可能决定了22q11DS中精神疾病的高发病率和神经学软体征的存在。神经学软体征被定义为在运动和感觉任务检查中表现异常但无局灶性神经功能缺损。COMT单倍体不足、DA功能障碍和白质异常可能导致22q11DS中神经学软体征的出现。
