Al-Kateb Hussam, Khanna Geetika, Filges Isabel, Hauser Natalie, Grange Dorothy K, Shen Joseph, Smyser Christopher D, Kulkarni Shashikant, Shinawi Marwan
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri.
Am J Med Genet A. 2014 May;164A(5):1118-26. doi: 10.1002/ajmg.a.36401. Epub 2014 Jan 23.
The typical chromosome 16p11.2 rearrangements are estimated to occur at a frequency of approximately 0.6% of all samples tested clinically and have been identified as a major cause of autism spectrum disorders, developmental delay, behavioral abnormalities, and seizures. Careful examination of patients with these rearrangements revealed association with abnormal head size, obesity, dysmorphism, and congenital abnormalities. In this report, we extend this list of phenotypic abnormalities to include scoliosis and vertebral anomalies. We present detailed characterization of phenotypic and radiological data of 10 new patients, nine with the 16p11.2 deletion and one with the duplication within the coordinates chr16:29,366,195 and 30,306,956 (hg19) with a minimal size of 555 kb. We discuss the phenotypical and radiological findings in our patients and review 5 previously reported patients with 16p11.2 rearrangement and similar skeletal abnormalities. Our data suggest that patients with the recurrent 16p11.2 rearrangement have increased incidence of scoliosis and vertebral anomalies. However, additional studies are required to confirm this observation and to establish the incidence of these anomalies. We discuss the potential implications of our findings on the diagnosis, surveillance and genetic counseling of patients with 16p11.2 rearrangement.
据估计,典型的16p11.2染色体重排在所有临床检测样本中的发生频率约为0.6%,并且已被确定为自闭症谱系障碍、发育迟缓、行为异常和癫痫发作的主要原因。对有这些重排的患者进行仔细检查后发现,他们还伴有头部大小异常、肥胖、畸形和先天性异常。在本报告中,我们将这一系列表型异常扩展至包括脊柱侧弯和椎体异常。我们展示了10例新患者的详细表型和放射学数据特征,其中9例为16p11.2缺失,1例为在坐标chr16:29,366,195和30,306,956(hg19)范围内的重复,最小大小为555 kb。我们讨论了我们患者的表型和放射学发现,并回顾了5例先前报道的有16p11.2重排及类似骨骼异常的患者。我们的数据表明,复发性16p11.2重排的患者脊柱侧弯和椎体异常的发生率增加。然而,需要进一步的研究来证实这一观察结果并确定这些异常的发生率。我们讨论了我们的发现对16p11.2重排患者的诊断、监测和遗传咨询的潜在影响。