Clinical Genetics, Department of Pediatrics, Albert Einstein Medical Center, Philadelphia, PA, USA.
BMC Med Genet. 2009 Dec 16;10:137. doi: 10.1186/1471-2350-10-137.
Anophthalmia and microphthalmia are etiologically and clinically heterogeneous. Lenz microphthalmia is a syndromic form that is typically inherited in an X-linked pattern, though the causative gene mutation is unknown. Townes-Brocks syndrome manifests thumb anomalies, imperforate anus, and ear anomalies. We present a 13-year-old boy with a syndromic microphthalmia phenotype and a clinical diagnosis of Lenz microphthalmia syndrome.
The patient was subjected to clinical and molecular evaluation, including array CGH analysis. The clinical features included left clinical anophthalmia, right microphthalmia, anteriorly placed anus with fistula, chordee, ventriculoseptal defect, patent ductus arteriosus, posteriorly rotated ears, hypotonia, growth retardation with delayed bone age, and mental retardation. The patient was found to have an approximately 5.6 Mb deletion of 16q11.2q12.1 by microarray based-comparative genomic hybridization, which includes the SALL1 gene, which causes Townes-Brocks syndrome.
Deletions of 16q11.2q12.2 have been reported in several individuals, although those prior reports did not note microphthalmia or anophthalmia. This region includes SALL1, which causes Townes-Brocks syndrome. In retrospect, this child has a number of features that can be explained by the SALL1 deletion, although it is not clear if the microphthalmia is a rare feature of Townes-Brocks syndrome or caused by other mechanisms. These data suggest that rare copy number changes may be a cause of syndromic microphthalmia allowing a personalized genomic medicine approach to the care of patients with these aberrations.
无眼症和小眼球症在病因和临床方面具有异质性。Lenz 小眼症是一种综合征形式，通常以 X 连锁模式遗传，但致病基因突变尚不清楚。唐氏综合征表现为拇指异常、肛门闭锁和耳部异常。我们报告了一例 13 岁男孩，具有综合征性小眼畸形表型和 Lenz 小眼症综合征的临床诊断。
患者接受了临床和分子评估，包括 array CGH 分析。临床特征包括左眼临床无眼症、右眼小眼球症、肛门前置伴瘘管、阴茎下弯、室间隔缺损、动脉导管未闭、耳后旋、肌张力低下、生长迟缓伴骨龄延迟和智力障碍。患者发现存在约 5.6Mb 的 16q11.2q12.1 缺失，该缺失包括导致唐氏综合征的 SALL1 基因。
16q11.2q12.2 缺失已在数名个体中报道，尽管先前的报道未注意到小眼球症或无眼症。该区域包括导致唐氏综合征的 SALL1 基因。回顾性分析，该患儿有许多特征可归因于 SALL1 缺失，尽管小眼球症是否为唐氏综合征的罕见特征或由其他机制引起尚不清楚。这些数据表明，罕见的拷贝数变化可能是综合征性小眼球症的病因，从而为这些异常患者的个体化基因组医学治疗方法提供了依据。
