Tartaglia Nicole, Davis Shanlee, Hench Alison, Nimishakavi Sheela, Beauregard Renee, Reynolds Ann, Fenton Laura, Albrecht Lindsey, Ross Judith, Visootsak Jeannie, Hansen Robin, Hagerman Randi
Department of Pediatrics, University of Colorado Denver, School of Medicine, Aurora, Colorado, USA.
Am J Med Genet A. 2008 Jun 15;146A(12):1509-22. doi: 10.1002/ajmg.a.32366.
XXYY syndrome occurs in approximately 1:18,000-1:40,000 males. Although the physical phenotype is similar to 47,XXY (tall stature, hypergonadotropic hypogonadism, and infertility), XXYY is associated with additional medical problems and more significant neurodevelopmental and psychological features. We report on the results of a cross-sectional, multi-center study of 95 males age 1-55 with XXYY syndrome (mean age 14.9 years), describing diagnosis, physical features, medical problems, medications, and psychological features stratified by age groups. The mean age of diagnosis was 7.7 years. Developmental delays and behavioral problems were the most common primary indication for genetic testing (68.4%). Physical and facial features varied with age, although hypertelorism, clinodactyly, pes planus, and dental problems were common across all age groups. Tall stature was present in adolescents and adults, with a mean adult stature of 192.4 cm (SD 7.5; n = 22). Common medical problems included allergies and asthma (>50%), congenital heart defects (19.4%), radioulnar synostosis (17.2%), inguinal hernia and/or cryptorchidism (16.1%), and seizures (15%). Medical features in adulthood included hypogonadism (100%), DVT (18.2%), intention tremor (71%) and type II diabetes (18.2%). Brain MRI (n = 35) showed white matter abnormalities in 45.7% of patients and enlarged ventricles in 22.8%. Neurodevelopmental and psychological difficulties were a significant component of the behavioral phenotype, with developmental delays and learning disabilities universal but variable in severity. Twenty-six percent had full-scale IQs in the range of intellectual disability (MR), and adaptive functioning was significantly impacted with 68% with adaptive composite scores <70. Rates of neurodevelopmental disorders, including ADHD (72.2%), autism spectrum disorders (28.3%), mood disorders (46.8%), and tic disorders (18.9%), were elevated with 55.9% on psychopharmacologic medication overall. Recommendations for evaluation and treatment are summarized.
XXYY综合征在男性中的发病率约为1/18000至1/40000。虽然其身体表型与47,XXY相似（身材高大、高促性腺激素性性腺功能减退和不育），但XXYY综合征还伴有其他医学问题以及更显著的神经发育和心理特征。我们报告了一项针对95名年龄在1至55岁的XXYY综合征男性患者（平均年龄14.9岁）的横断面多中心研究结果，描述了诊断情况、身体特征、医学问题、用药情况以及按年龄组分层的心理特征。诊断的平均年龄为7.7岁。发育迟缓与行为问题是基因检测最常见的主要指征（68.4%）。身体和面部特征随年龄而异，不过眼距过宽、小指内弯、扁平足和牙齿问题在所有年龄组中都很常见。青少年和成年人中存在身材高大的情况，成年人的平均身高为192.4厘米（标准差7.5；n = 22）。常见的医学问题包括过敏和哮喘（>50%）、先天性心脏缺陷（19.4%）、桡尺骨融合（17.2%）、腹股沟疝和/或隐睾症（16.1%）以及癫痫发作（15%）。成年期的医学特征包括性腺功能减退（100%）、深静脉血栓形成（18.2%）、意向性震颤（71%）和II型糖尿病（18.2%）。脑部磁共振成像（n = 35）显示，45.7%的患者存在白质异常，22.8%的患者脑室扩大。神经发育和心理困难是行为表型的重要组成部分，发育迟缓和学习障碍普遍存在，但严重程度各不相同。26%的患者全量表智商处于智力残疾（MR）范围内，适应性功能受到显著影响，68%的患者适应性综合得分<70。神经发育障碍的发生率有所升高，包括注意力缺陷多动障碍（ADHD，72.2%）、自闭症谱系障碍（28.3%）、情绪障碍（46.8%）和抽动障碍（18.9%），总体上55.9%的患者正在服用精神药物。文中总结了评估和治疗的建议。
