Skuse David, Printzlau Frida, Wolstencroft Jeanne
Brain and Behaviour Science Unit, UCL Institute of Child Health, London, United Kingdom.
Brain and Behaviour Science Unit, UCL Institute of Child Health, London, United Kingdom.
Handb Clin Neurol. 2018;147:355-376. doi: 10.1016/B978-0-444-63233-3.00024-5.
Sex chromosome aneuploidies comprise a relatively common group of chromosome disorders characterized by the loss or gain of one or more sex chromosomes. We discuss five of the better-known sex aneuploidies: Turner syndrome (XO), Klinefelter syndrome (XXY), trisomy X (XXX), XYY, and XXYY. Despite their prevalence in the general population, these disorders are underdiagnosed and the specific genetic mechanisms underlying their phenotypes are poorly understood. Although there is considerable variation between them in terms of associated functional impairment, each disorder has a characteristic physical, cognitive, and neurologic profile. The most common cause of sex chromosome aneuploidies is nondisjunction, which can occur during meiosis or during the early stages of postzygotic development. The loss or gain of genetic material can affect all daughter cells or it may be partial, leading to tissue mosaicism. In both typical and atypical sex chromosome karyotypes, there is random inactivation of all but one X chromosome. The mechanisms by which a phenotype results from sex chromosome aneuploidies are twofold: dosage imbalance arising from a small number of genes that escape inactivation, and their endocrinologic consequences.
性染色体非整倍体是一组相对常见的染色体疾病，其特征是一条或多条性染色体的丢失或增加。我们讨论五种较为知名的性染色体非整倍体：特纳综合征（XO）、克兰费尔特综合征（XXY）、三体X（XXX）、XYY和XXYY。尽管这些疾病在普通人群中普遍存在，但它们的诊断不足，其表型背后的具体遗传机制也知之甚少。尽管它们在相关功能损害方面存在相当大的差异，但每种疾病都有其特征性的身体、认知和神经学特征。性染色体非整倍体最常见的原因是不分离，这可能发生在减数分裂期间或合子后发育的早期阶段。遗传物质的丢失或增加可能会影响所有子细胞，也可能是部分性的，导致组织嵌合体。在典型和非典型性染色体核型中，除了一条X染色体外，所有其他X染色体都会随机失活。性染色体非整倍体产生表型的机制有两个方面：少数逃避失活的基因导致的剂量失衡及其内分泌后果。
