CHARGE syndrome

CHARGE syndrome was initially defined as a non-random association of anomalies (Coloboma, Heart defect, Atresia choanae, Retarded growth and development, Genital hypoplasia, Ear anomalies/deafness). In 1998, an expert group defined the major (the classical 4C's: Choanal atresia, Coloboma, Characteristic ears and Cranial nerve anomalies) and minor criteria of CHARGE syndrome. Individuals with all four major characteristics or three major and three minor characteristics are highly likely to have CHARGE syndrome. However, there have been individuals genetically identified with CHARGE syndrome without the classical choanal atresia and coloboma. The reported incidence of CHARGE syndrome ranges from 0.1–1.2/10,000 and depends on professional recognition. Coloboma mainly affects the retina. Major and minor congenital heart defects (the commonest cyanotic heart defect is tetralogy of Fallot) occur in 75–80% of patients. Choanal atresia may be membranous or bony; bilateral or unilateral. Mental retardation is variable with intelligence quotients (IQ) ranging from normal to profound retardation. Under-development of the external genitalia is a common finding in males but it is less apparent in females. Ear abnormalities include a classical finding of unusually shaped ears and hearing loss (conductive and/or nerve deafness that ranges from mild to severe deafness). Multiple cranial nerve dysfunctions are common. A behavioral phenotype for CHARGE syndrome is emerging. Mutations in the CHD7 gene (member of the chromodomain helicase DNA protein family) are detected in over 75% of patients with CHARGE syndrome. Children with CHARGE syndrome require intensive medical management as well as numerous surgical interventions. They also need multidisciplinary follow up. Some of the hidden issues of CHARGE syndrome are often forgotten, one being the feeding adaptation of these children, which needs an early aggressive approach from a feeding team. As the child develops, challenging behaviors become more common and require adaptation of educational and therapeutic services, including behavioral and pharmacological interventions

Feasibility and initial experience of left radial approach for diagnostic neuroangiography.

Neuroangiography has seen a recent shift from transfemoral to transradial access. In transradial neuroangiography, the right dominant hand is the main access used. However, the left side may be used specifically for left posterior circulation pathologies and when right access cannot be used. This study describes our initial experience with left radial access for diagnostic neuroangiography and assesses the feasibility and safety of this technique. We performed a retrospective review of a prospective database of consecutive patients between April 2018 and January 2020, and identified 20 patients whom a left radial access was used for neurovascular procedures. Left transradial neuroangiography was successful in all 20 patients and provided the sought diagnostic information; no patient required conversion to right radial or femoral access. Pathology consisted of anterior circulation aneurysms in 17 patients (85%), brain tumor in 1 patient (5%), and intracranial atherosclerosis disease involving the middle cerebral artery in 2 patients (10%). The left radial artery was accessed at the anatomic snuffbox in 18 patients (90%) and the wrist in 2 patients (10%). A single vessel was accessed in 7 (35%), two vessels in 8 (40%), three vessels in 4 (20%), and four vessels in 1 (5%). Catheterization was successful in 71% of the cases for the right internal carotid artery and in only 7.7% for the left internal carotid artery. There were no instances of radial artery spasm, radial artery occlusion, or procedural complications. Our initial experience found the left transradial access to be a potentially feasible approach for diagnostic neuroangiography even beyond the left vertebral artery. The approach is strongly favored by patients but has significant limitations compared with the right-sided approach

Heterozygous ANKRD17 loss-of-function variants cause a syndrome with intellectual disability, speech delay, and dysmorphism

ANKRD17 is an ankyrin repeat-containing protein thought to play a role in cell cycle progression, whose ortholog in Drosophila functions in the Hippo pathway as a co-factor of Yorkie. Here, we delineate a neurodevelopmental disorder caused by de novo heterozygous ANKRD17 variants. The mutational spectrum of this cohort of 34 individuals from 32 families is highly suggestive of haploinsufficiency as the underlying mechanism of disease, with 21 truncating or essential splice site variants, 9 missense variants, 1 in-frame insertion-deletion, and 1 microdeletion (1.16 Mb). Consequently, our data indicate that loss of ANKRD17 is likely the main cause of phenotypes previously associated with large multi-gene chromosomal aberrations of the 4q13.3 region. Protein modeling suggests that most of the missense variants disrupt the stability of the ankyrin repeats through alteration of core structural residues. The major phenotypic characteristic of our cohort is a variable degree of developmental delay/intellectual disability, particularly affecting speech, while additional features include growth failure, feeding difficulties, non-specific MRI abnormalities, epilepsy and/or abnormal EEG, predisposition to recurrent infections (mostly bacterial), ophthalmological abnormalities, gait/balance disturbance, and joint hypermobility. Moreover, many individuals shared similar dysmorphic facial features. Analysis of single-cell RNA-seq data from the developing human telencephalon indicated ANKRD17 expression at multiple stages of neurogenesis, adding further evidence to the assertion that damaging ANKRD17 variants cause a neurodevelopmental disorder.Neurolog