The guts of it

The aim of this presentation is to discuss the gastrointestinal (GI) symptoms and feeding difficulties in CHARGE syndrome. Much of this presentation is based on the review paper titled “Gastrointestinal and feeding difficulties in CHARGE syndrome: A review from head-to-toe”, authors Kim D. Blake, Alexandra S. Hudson American Journal Medical Genetics 2017; 1-11. This review paper is a useful resource for professionals and parents who want an overview of the GI issues in CHARGE syndrome.
The structural abnormalities, motility impairment and sensory impairment all contribute to the GI issues and are potential treatment targets. I will describe how cranial nerve abnormalities underlines the pervasive GI dysfunction and the need for further research on gut motility and the microbiome.


A Review From Head-To-Toe

CHARGE syndrome is an autosomal dominant genetic condition that is primarily diagnosed based on clinical features, with genetic testing available for confirmation. The CHARGE mnemonic stands for some of the common characteristics: coloboma, heart defects, atresia/stenosis of the choanae, retardation of growth/development, genitourinary anomalies, and ear abnormalities (CHARGE). However, many of the common clinical features are not captured by this mnemonic, including cranial nerve dysfunction, considered by some to be one of the major diagnostic criteria. Over 90%of individuals experience feeding and gastrointestinal dysfunction, which carries great morbidity and mortality. The aim of this review is to examine the nature of gastrointestinal (GI) symptoms and feeding difficulties in CHARGE syndrome, focusing on their underlying pathology, associated investigations, and available treatment options. We also provide information on available tools (for parents, clinicians, and researchers) that are important additions to the lifelong healthcare management of every individual with CHARGE syndrome. We review how cranial nerve dysfunction is one of the most important characteristics underlying the pervasive GI and feeding dysfunction, and discuss the need for future research on gut innervation and motility in this genetic disorder.

CHARGE syndrome, cranial nerve dysfunction, feeding difficulties, gastrointestinal dysfunction, gut motility


Zebrafish Model

CHARGE syndrome is linked to autosomal-dominant mutations in the CHD7 gene and results in a number of physiological and structural abnor-malities, including heart defects, hearing and vision loss, and gastrointesti-nal (GI) problems. Of these challenges, GI problems have a profound impact throughout an individual’s life, resulting in increased morbidity and mortality. A homolog of CHD7 has been identified in the zebrafish, the loss of which recapitulates many of the features of the human disease. Using a morpholino chd7 knockdown model complemented by a chd7 null mutant zebrafish line, we examined GI structure, innervation, and motility in larval zebrafish. Loss of chd7 resulted in physically smaller GI tracts with normal epithelial and muscular histology, but decreased and disorga-nized vagal projections, particularly in the foregut. chd7 morphant larvae had significantly less ability to empty their GI tract of gavaged fluorescent beads, and this condition was only minimally improved by the prokinetic agents, domperidone and erythromycin, in keeping with mixed responses to these agents in patients with CHARGE syndrome. The conserved genetics and transparency of the zebrafish have provided new insights into the con-sequences of chd7 gene dysfunction on the GI system and cranial nerve patterning. These findings highlight the opportunity of the zebrafish to serve as a preclinical model for studying compounds that may improve GI motility in individuals with CHARGE syndrome.


CHARGE Syndrome Check-List

CHARGE Syndrome Check-List

A comprehensive approach to health screening and management for individuals with CHARGE syndrome is essential. We developed a checklist organized by body system and age to guide the healthcare provider in their approach to care. The checklist was evaluated using a modified Delphi method to develop a final consensus.

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Abbreviations Used in Checklist

CGH E comparative genomic hybridization
CNS E central nervous system CT E computed tomography DEXA scan E dual energy XEray absorptiometry
EEG E electroencephalogram ENT E ear, nose and throat
FSH E follicle stimulating hormone
GH E growth hormone
HRT E hormone replacement therapy LH E luteinizing hormone
MRI E magnetic resonance imaging MSK E musculoskeletal
U/S E ultrasound
VCUG E voiding cystourethrogram


Blake K, Prasad C. 2006. CHARGE syndrome. Orphanet J Rare Dis 1: 34

Brown D. 2005. CHARGE syndrome “behaviors”: challenges or adaptations? Am J Med Genet Part A 133A: 268E272
Hsu P, Ma A, Wilson M, Williams G, Curotta J, Munns CF, Mehr S. 2014. CHARGE syndrome: a review. J Pediatr Child Health 50: 504E511