Background

Adams–Oliver syndrome (AOS) is a rare, inherited multi-systemic malformation syndrome characterized by a combination of aplasia cutis congenita and transverse terminal limb defects along with variable involvement of the central nervous system, eyes, and cardiovascular system. AOS can be inherited as both autosomal-dominant and recessive traits. Pathogenic variants in the DOCK6, ARHGAP31, EOGT, RBPJ, DLL4, and NOTCH1 genes have been associated with AOS.

Purpose

To report a novel homozygous variant in the DOCK6 gene associated with Adams–Oliver syndrome type 2.

Materials and methods

Case report.

Results

We report a case of a 4-month-old male who presented with microcephaly, global developmental delay, truncal hypotonia, and limb reduction defects. Ophthalmic examination revealed bilateral nystagmus and retinal detachment with mild cataractous changes in addition to retrolental plaque in the left eye. Next generation sequencing analysis identified a novel homozygous frameshift likely pathogenic variant (c.1269_1285dup (p.Arg429Glnfs*32)) in the DOCK6 gene. The constellation of the clinical findings and the genetic mutation were consistent with a diagnosis of AOS type 2.

Conclusion

The discovery of this new likely pathogenic variant enriches the genotypic spectrum of DOCK6 gene and contributes to genetic diagnosis and counseling of families with AOS. Neurologic and ocular findings appear to be consistent with AOS type 2 for which multidisciplinary clinical evaluation is crucial.

中文翻译：

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与2型Adams-Oliver综合征相关的DOCK6基因的新变异。

背景

亚当斯-奥利弗综合症（AOS）是一种罕见的遗传性多系统畸形综合症，其特征是先天性发育不良和横向末梢肢体缺损以及中枢神经系统，眼睛和心血管系统的受累程度相结合。AOS可以作为常染色体显性和隐性性状遗传。DOCK6，ARHGAP31，EOGT，RBPJ，DLL4和NOTCH1基因中的致病变异与AOS相关。

目的

报告DOCD6基因中与Adams–Oliver综合征2型有关的新型纯合变异。

材料和方法

案例报告。

结果

我们报告了一个4个月大的男性病例，该男性表现为小头畸形，整体发育迟缓，截断性肌张力低下和四肢复位缺损。眼科检查显示左眼双侧眼球震颤和视网膜脱离，伴有轻度白内障改变，以及左眼后斑。下一代测序分析在DOCK6基因中鉴定了一种新型的纯合移码可能致病变异（c.1269_1285dup（p.Arg429Glnfs * 32））。临床结果和遗传突变的星座与2型AOS的诊断一致。

结论

这一新的可能的致病变异体的发现丰富了DOCK6基因的基因型谱，并有助于AOS家庭的遗传诊断和咨询。神经学和眼部检查结果似乎与2型AOS一致，对于AOS 2型，多学科临床评估至关重要。