CHARGE syndrome: Report of 47 cases and review

Abstract

The acronym CHARGE refers to a syndrome of unknown cause. Here we report on 47 CHARGE patients evaluated for the frequency of major anomalies, namely coloboma (79%), heart malformation (85%), choanal atresia (57%), growth and/or mental retardation (100%), genital anomalies (34%), ear anomalies (91%), and/or deafness (62%). In addition, we comment on anomalies observed very frequently in neonates and infants with the CHARGE syndrome, including, minor facial anomalies, neonatal brain stem dysfunction with cranial nerve palsy, and, mostly, internal ear anomalies such as semicircular canal hypoplasia that were found in each patient that could be tested. We propose several criteria for poor survival including male gender, central nervous system and/or oesophageal malformations, and bilateral choanal atresia. No predictive factor regarding developmental prognosis could be identified in our series. A significantly higher mean paternal age at conception together with concordance in monozygotic twins and the existence of rare familial cases support the role of genetic factors such as de novo mutation of a dominant gene or subtle sub-microscopic chromosome rearrangement. Finally, the combination of malformations in CHARGE syndrome strongly supports the view that this multiple congenital anomalies/mental retardation syndrome is a polytopic developmental field defect involving the neural tube and the neural crests cells.

Kallmann syndrome

“…Consequently, previously reported KS cases associated with congenital heart disease 44 or choanal atresia 45 could in fact represent unrecognised mild CHARGE cases. 46 CHARGE syndrome shares additional traits with the KAL2 genetic form of KS (see below), including cleft lip or palate, present in 20 -35% of KAL2 7,11 -13 and CHARGE 47 patients, external ear malformation, noted in virtually all CHARGE patients 47 and a few KAL2 patients, 48 agenesis of the corpus callosum, reported in several CHARGE 47 and KAL2 patients, 7,13 and coloboma that is highly prevalent in CHARGE patients 47 and has been reported in at least one KAL2 patient too. 7 Most individuals with CHARGE syndrome are heterozygous for loss-of-function mutations in CHD7 that encodes a chromodomain (chromatin organisation modifier domain) helicase DNA-binding protein.…”

Behavior in CHARGE syndrome: Introduction to the special topic

“…Gross motor delay in children with CHARGE can be attributed in large part to vestibular dysfunction since the Mondini defect and the associated vestibular anomalies are a frequent finding [Tellier et al, 1998;Wiener-Vacher et al, 1999;Satar et al, 2003]. However, the delay can also be affected by lack of upper visual fields secondary to ocular…”

Distinct cerebellar foliation anomalies in a CHD7 haploinsufficient mouse model of CHARGE syndrome

“…Neuroanatomical anomalies have been reported in CHARGE syndrome (Becker, Stiemer, Neumann, & Entezami, 2001; Bergman, Bocca, Hoefsloot, Meiners, & van Ravenswaaij‐Arts, 2011; Issekutz, Prasad, Smith, & Blake, 2005; Lin et al, 1990; Sanlaville et al, 2006; Sanlaville & Verloes, 2007; Tellier et al, 1998). Lin et al (1990) identified CNS anomalies in 55% ( n  = 26/47) and Tellier et al (1998) in 79% ( n  = 37/47) of CHARGE syndrome patients.…”