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This review evaluates the current evidence for the clinical management of congenital internal carotid artery hypoplasia (CICAH). We summarise clinical presentations diagnostic standards, imaging recommendations, treatment and follow-up. The review was prompted by a case of CICAH in a 50-year-old female who presented to our neurosurgery clinic with an acute episode of vertigo. The patient underwent CT angiogram, which showed an unusually low right carotid bifurcation. The right internal carotid artery (ICA) was hypoplastic, and the A1 segment of the anterior cerebral artery (ACA) was absent. Skull base CT showed an ipsilateral hypoplastic carotid canal. To summarise current evidence for clinical management of CICAH we followed PRISMA guidelines to identify papers meeting our predefined inclusion criteria. We searched three databases using the terms 'ICA' and 'Hypoplasia'. We reviewed 41 papers meeting our criteria. 34 were clinical reports. We performed a data extraction and quality appraisal on these reports. We found that CICAH may be less rare than previously described. Blood pressure control in CICAH is crucial due to the increased risk of stroke and aneurysm formation. Follow-up imaging is strongly recommended. Carotid doppler sonography is a powerful and underutilised diagnostic tool, and carotid canal hypoplasia is not a pathognomic sign. In conclusion, clinicians should be alert to anatomic variations such as CICAH because these produce haemodynamic changes that may have serious clinical consequences. We recommend a central registry of patients with CICAH in order to understand the longer-term natural history of the condition. [ABSTRACT FROM AUTHOR]

Structural variation is widespread in mammalian genomes (1,2) and is an important cause of disease (3), but just how abundant and important structural variants (SVs) are in shaping phenotypic variation remains unclear (4,5). Without knowing how many SVs there are, and how they arise, it is difficult to discover what they do. Combining experimental with automated analyses, we identified 711,920 SVs at 281,243 sites in the genomes of thirteen classical and four wild-derived inbred mouse strains. The majority of SVs are less than 1 kilobase in size and 98% are deletions or insertions. The breakpoints of 160,000 SVs were mapped to base pair resolution, allowing us to infer that insertion of retrotransposons causes more than half of SVs. Yet, despite their prevalence, SVs are less likely than other sequence variants to cause gene expression or quantitative phenotypic variation. We identified 24 SVs that disrupt coding exons, acting as rare variants of large effect on gene function. One-third of the genes so affected have immunological functions., The pre-eminent organism for modelling the relationship between phenotype and genotype, including SVs, is the mouse, but our catalogue of SVs in this animal is incomplete (6) and most of [...]

Brain morphogenesis is an important process contributing to higher-order cognition, however our knowledge about its biological basis is largely incomplete. Here we analyze 118 neuroanatomical parameters in 1,566 mutant mouse lines and identify 198 genes whose disruptions yield NeuroAnatomical Phenotypes (NAPs), mostly affecting structures implicated in brain connectivity. Groups of functionally similar NAP genes participate in pathways involving the cytoskeleton, the cell cycle and the synapse, display distinct fetal and postnatal brain expression dynamics and importantly, their disruption can yield convergent phenotypic patterns. 17% of human unique orthologues of mouse NAP genes are known loci for cognitive dysfunction. The remaining 83% constitute a vast pool of genes newly implicated in brain architecture, providing the largest study of mouse NAP genes and pathways. This offers a complementary resource to human genetic studies and predict that many more genes could be involved in mammalian brain morphogenesis. Brain morphogenesis is an important process contributing to higher-order cognition, however our knowledge about its biological basis is largely incomplete. Here, authors analyzed 118 neuroanatomical parameters in 1,566 mutant mouse lines to identify 198 genes whose disruptions yield neuroanatomical phenotypes [ABSTRACT FROM AUTHOR]