Search

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. [ABSTRACT FROM AUTHOR]

The TBL1XR1 gene product is a nuclear protein ubiquitously produced. The protein is a component of SMRT/N-CoR co-repressor complexes and participates in the molecular switch of specific gene transcription. Deletions of the TBL1XR1 gene have been described in two families to date, both presenting intellectual disability and dysmorphisms. Rare recurrent chromosomal micro-rearrangements, particularly those involving single genes, represent a challenge for clinicians to ensure correlation with phenotype due to the paucity of previously described cases. Here we present a patient harbouring a TBL1XR1 gene deletion detected by chromosome microarray analysis. In addition to intellectual disability, the patient presents dysmorphic features and multiple cardiac malformations, together with brain malformation, thus contributing to the phenotypic characterization of this rare microdeletion and to the TBL1XR1 gene function. [ABSTRACT FROM AUTHOR]

Abstract: We describe two Finnish brothers with frontotemporal pachygyria, intellectual deficiency and mild dysmorphisms. Previously, only a few cases of similar frontotemporal pachygyria have been reported. This report provides further evidence about frontotemporal pachygyria being a distinct genetic entity inherited as an autosomal recessive trait. [Copyright &y& Elsevier]

Abstract: Coffin–Siris syndrome or “fifth digit” syndrome is a multiple congenital anomaly-mental retardation syndrome with severe developmental delay, coarse facial features, hirsutism and absent fifth fingernails or toenails or fifth distal phalanges. The etiology of this syndrome remains uncertain. Here we report a stillborn male baby born from consanguineous parents who might represent a very severe form of Coffin–Siris syndrome with cardiac defect and multiple brain malformations including corpus callosum agenesis and Dandy Walker malformation. To the best of our knowledge, it is the first case leading to intrauterine death. Karyotype and array comparative genomic hybridization were normal; these results give additional support to mendelian inheritance for this syndrome. In our family, the most likely mode of inheritance is autosomal recessive and the recurrence is probably as high as 25%. [ABSTRACT FROM AUTHOR]