CHARGE

CHARGE
Name	CHARGE
Specialty	Medical genetics, Otolaryngology, Ophthalmology

CHARGE.

Overview

CHARGE is a complex congenital syndrome first characterized in case series from the late 20th century and subsequently linked to mutations in the CHD7 locus. It encompasses a constellation of anomalies affecting craniofacial, sensory, cardiac, and endocrine structures described in pediatric, genetic, and otolaryngologic literature, including reports in journals such as The New England Journal of Medicine, Nature Genetics, The Lancet, JAMA, and Pediatrics. Recognition of CHARGE influenced practice guidelines from professional bodies including the American Academy of Pediatrics and multidisciplinary care models seen at centers like Boston Children's Hospital, Great Ormond Street Hospital, Mayo Clinic, and Johns Hopkins Hospital.

Signs and symptoms

Affected individuals commonly present with coloboma of the eye linked to anomalies reported in ophthalmologic series alongside cranial nerve dysfunction documented in studies from Harvard Medical School, Stanford University School of Medicine, and University College London. Ear malformations and sensorineural hearing loss are frequent, with audiologic management referenced in guidelines from the American Academy of Otolaryngology–Head and Neck Surgery and case reviews from Massachusetts Eye and Ear. Cardiac defects include conotruncal and septal anomalies such as tetralogy of Fallot and atrial septal defects managed in centers like Texas Children's Hospital and Great Ormond Street Hospital. Choanal atresia and airway anomalies described in pediatric otolaryngology texts often prompt early intervention coordinated with neonatal units at institutions like Sheba Medical Center and SickKids (Hospital for Sick Children). Feeding difficulties, growth failure, and endocrine dysfunction including hypogonadotropic hypogonadism have been detailed in endocrine series from Mayo Clinic and Karolinska Institutet. Developmental delay, intellectual disability, and autistic features are reported across neurodevelopmental cohorts studied at Kennedy Krieger Institute, Seattle Children's Hospital, and Children's Hospital of Philadelphia.

Genetics and pathophysiology

Pathogenic variants in the ATP-dependent chromatin remodeler gene CHD7 on chromosome 8 are the predominant genetic cause, with loss-of-function mutations elucidated in molecular studies published in Nature, American Journal of Human Genetics, and Genetics in Medicine. CHD7 protein interacts with chromatin regulators characterized in studies from Cold Spring Harbor Laboratory, Broad Institute, and Max Planck Institute and impacts neural crest cell development, cranial nerve patterning, and organogenesis described in model organism research from Harvard University, University of Cambridge, and Stanford University. Genotype–phenotype correlations remain imprecise but have been explored in multicenter cohorts from European Society of Human Genetics, International CHARGE Syndrome Foundation, and national registries in Sweden, France, and the United States. Rare cases without identifiable CHD7 variants implicate other loci reported in consortium studies involving The Wellcome Trust Sanger Institute and European Molecular Biology Laboratory.

Diagnosis

Diagnosis combines clinical diagnostic criteria established in consensus statements from experts affiliated with American College of Medical Genetics and Genomics, European Society of Pediatric Endocrinology, and specialty centers such as Boston Children's Hospital. Major features prioritized in protocols include ocular coloboma, choanal atresia or cleft, characteristic ear anomalies, and cranial nerve dysfunction; genetic confirmation via sequencing of CHD7 using methods standardized by laboratories accredited by College of American Pathologists and guidelines from the American College of Medical Genetics and Genomics is recommended. Imaging modalities—computed tomography protocols refined at Mayo Clinic Radiology Department, magnetic resonance imaging approaches from Johns Hopkins Radiology, and echocardiography techniques championed by Cleveland Clinic—support structural assessment. Differential diagnosis includes syndromes cataloged in databases such as Online Mendelian Inheritance in Man and evaluated against conditions reported by consortia at Genomics England and ClinGen.

Management and treatment

Management requires coordinated multidisciplinary care involving teams described in care models at Great Ormond Street Hospital, Boston Children's Hospital, Johns Hopkins Hospital, Mayo Clinic, and The Children's Hospital of Philadelphia. Interventions include ophthalmologic surgery documented in series from Moorfields Eye Hospital, otologic hearing rehabilitation with cochlear implantation programs at Cochlear Limited-affiliated centers and implant centers like House Ear Institute, cardiac surgery guided by protocols from Society of Thoracic Surgeons and pediatric cardiology teams at Texas Children's Hospital, airway surgery informed by reports from University of Michigan Health, and feeding/communication support via speech and occupational therapy programs similar to those at Kennedy Krieger Institute. Endocrine management, growth hormone assessment, and fertility counseling follow practice statements by Endocrine Society and case series from Karolinska Universitetssjukhuset. Genetic counseling is provided per standards from the National Society of Genetic Counselors and family support through organizations like the International CHARGE Syndrome Foundation and national patient advocacy groups in Canada, Australia, and United Kingdom.

Epidemiology and prognosis

Epidemiologic estimates from country-level surveillance, including registries in the United States, Denmark, Netherlands, and Australia, indicate a prevalence on the order of 1 in 8,000 to 1 in 15,000 live births, with ascertainment varying by referral patterns to tertiary centers such as Boston Children's Hospital and Great Ormond Street Hospital. Prognosis depends on severity of cardiac, respiratory, and feeding complications reported in longitudinal cohorts followed at Seattle Children's Hospital and SickKids (Hospital for Sick Children), with many individuals achieving improved survival and functional outcomes through early multidisciplinary interventions documented in outcome studies from Mayo Clinic and Johns Hopkins Hospital. Ongoing research initiatives at institutions like Broad Institute, Wellcome Sanger Institute, and consortiums under the European Reference Networks aim to refine natural history, genotype–phenotype relationships, and therapeutic strategies.

Category:Genetic disorders