Wallis Mathew, Baumer Alessandra, Smaili Wiam, Jaouad Imane Cherkaoui, Sefiani Abdelaziz, Jacobson Erica, Bowyer Lucy, Mowat David, Rauch Anita
Clinical Genetics Service, Austin Health, Heidelberg, Victoria, Australia; Department of Medicine, Austin Health, University of Melbourne, Australia.
Institute of Medical Genetics, University of Zurich, Australia.
Eur J Med Genet. 2018 Apr;61(4):189-196. doi: 10.1016/j.ejmg.2017.12.002. Epub 2017 Dec 7.
Non-syndromic congenital hydrocephalus is aetiologically diverse and while a genetic cause is frequently suspected, it often cannot be confirmed. The most common genetic cause is L1CAM-related X-linked hydrocephalus and that explains only 5%-10% of all male cases. This underlines a current limitation in our understanding of the genetic burden of non-syndromic congenital hydrocephalus, especially for those cases with likely autosomal recessive inheritance. Additionally, the prognosis for most cases of severe congenital hydrocephalus is poor, with most of the surviving infants displaying significant intellectual impairment despite surgical intervention. It is for this reason that couples with an antenatal diagnosis of severe hydrocephalus are given the option, and may opt, for termination of the pregnancy. We present two families with CCDC88C-related recessive congenital hydrocephalus with children who had severe hydrocephalus. Those individuals who were shunted within the first few weeks of life, who did not require multiple surgical revisions, and who had a more distal truncating variant of the CCDC88C gene met their early childhood developmental milestones in some cases. This suggests that children with CCDC88C-related autosomal recessive hydrocephalus can have normal developmental outcomes under certain circumstances. We recommend CCDC88C analysis in cases of severe non-syndromic congenital hydrocephalus, especially when aqueduct stenosis with or without a medial diverticulum is seen, in order to aid prognosis discussion.
非综合征性先天性脑积水病因多样，虽然常怀疑有遗传原因，但往往无法证实。最常见的遗传原因是与L1CAM相关的X连锁脑积水，这仅解释了所有男性病例的5%-10%。这凸显了我们目前对非综合征性先天性脑积水遗传负担理解的局限性，尤其是对于那些可能为常染色体隐性遗传的病例。此外，大多数严重先天性脑积水病例的预后较差，尽管进行了手术干预，但大多数存活婴儿仍表现出明显的智力障碍。正是出于这个原因，产前诊断为严重脑积水的夫妇可以选择，也可能选择终止妊娠。我们报告了两个患有与CCDC88C相关的隐性先天性脑积水的家庭，其孩子患有严重脑积水。那些在出生后几周内接受分流手术、不需要多次手术修正且CCDC88C基因有更远端截断变异的个体，在某些情况下达到了幼儿期发育里程碑。这表明，在某些情况下，患有与CCDC88C相关的常染色体隐性脑积水的儿童可以有正常的发育结果。我们建议在严重非综合征性先天性脑积水病例中进行CCDC88C分析，尤其是当出现伴有或不伴有内侧憩室的导水管狭窄时，以便有助于预后讨论。
