CHARGE Syndrome

Definition and epidemiology

The name CHARGE comes from the initials of the first features described: Coloboma of the eye, Heart defects, Atresia of the choanae, Retardation of growth and development, Genital hypoplasia and Ear anomalies with hearing loss. Most affected people carry a heterozygous pathogenic variant in CHD7; inheritance is autosomal dominant and the variant usually arises for the first time in the family (van Ravenswaaij-Arts et al., 2025). Because variants in the same gene produce a broad range, from the full picture to isolated inner ear findings, the term ‘CHD7 disorder’ is also used in current literature (Hale et al., 2016).

Three sets of clinical criteria have been developed. Blake et al. (1998) defined four major and seven minor criteria. Verloes (2005) reduced the major criteria to three findings, coloboma, choanal atresia and semicircular canal hypoplasia or aplasia, and introduced the distinction between typical, partial and atypical CHARGE. Hale et al. (2016), taking account of wider genetic testing, grouped cleft palate with choanal atresia and added external, middle or inner ear anomalies and a pathogenic CHD7 variant to the major criteria; two major criteria plus any number of minor criteria are sufficient for the diagnosis.

Birth prevalence has been reported as about 1 in 15,000 in the Netherlands and about 1 in 8,500 in Canada; with the spread of genomic testing, milder cases are also being recognised, which makes the true frequency harder to estimate (van Ravenswaaij-Arts et al., 2025).

Symptoms and signs

Ear findings are among the most consistent features of the syndrome. In people with a molecular diagnosis, an abnormal pinna has been reported in 90%, ossicular malformation in 80%, cochlear hypoplasia in 90% and semicircular canal anomalies in 94% (van Ravenswaaij-Arts et al., 2025). The pinna is typically short and wide with poorly defined folds and soft cartilage, and the two sides often look different. Hearing loss ranges from mild to profound and is frequently mixed: ossicular anomalies and persistent middle ear effusion produce the conductive component, while cochlear anomalies and nerve deficiency produce the sensorineural component. The sensorineural component is greater at high frequencies, and the combination can give a wedge-shaped audiogram (van Ravenswaaij-Arts et al., 2025).

Absent semicircular canals lead to vestibular areflexia in most children. Children do not complain of dizziness; instead, the problem appears as late head control, delayed sitting and walking, and difficulty with fine motor skills (van Ravenswaaij-Arts et al., 2025). In a prospective study of 17 children, semicircular canal anomalies were associated with delayed postural development, and no child with bilateral canal anomalies walked before 18 months (Abadie et al., 2000).

Coloboma occurs in about 80% and ranges from a small retinal coloboma to anophthalmia; visual field loss, light sensitivity, refractive error and a risk of retinal detachment may accompany it (van Ravenswaaij-Arts et al., 2025). The combination of visual and hearing loss (dual sensory loss), together with the balance problem, limits both the ways a child explores the surroundings and the ways they communicate. Involvement of other cranial nerves may cause loss of smell, facial palsy and swallowing difficulties.

Causes and risk factors

CHD7 encodes a protein that alters chromatin structure and so regulates the expression of many genes during development. Animal models show that it is needed for development of the inner ear, especially the semicircular canals, of the middle ear and of the auditory and vestibular nerve pathways (Choo et al., 2017). Loss of function of a single allele is enough to cause the condition. About 98% of identified pathogenic variants are found by sequence analysis and about 2% by deletion/duplication analysis (van Ravenswaaij-Arts et al., 2025).

In most cases the variant arises for the first time in the family; because one parent may have germline mosaicism, the recurrence risk for further children of unaffected parents is low but not zero. An affected person has a 50% chance of passing the variant to each child (van Ravenswaaij-Arts et al., 2025). Severity can differ considerably even within one family, and some people have only inner ear findings with mild facial features (Hale et al., 2016). CHD7 testing should therefore be considered in a child with hearing loss and semicircular canal aplasia even when other features are subtle.

Audiological and clinical assessment

Babies with CHARGE who pass newborn hearing screening still need a full audiological assessment for conductive and sensorineural loss (van Ravenswaaij-Arts et al., 2025). Testing is difficult because of visual impairment, breathing and feeding problems and frequent admissions. The risk of airway complications after sedation and anaesthesia is raised, so procedures needing anaesthesia should be kept to a minimum and combined in one session where possible (van Ravenswaaij-Arts et al., 2025).

• ABR: air- and bone-conduction ABR establish thresholds and the type of loss for each ear. Absent responses even at high stimulus levels make imaging for cochlear nerve deficiency essential.
• Tympanometry and acoustic reflexes: effusion from Eustachian tube dysfunction is common and makes the conductive component fluctuate. Acoustic reflexes are often absent because of ossicular anomalies and nerve deficiency; cases have been reported in which the electrically evoked stapedial reflex could not be recorded at cochlear implant surgery because the stapedius tendon was missing (Arndt et al., 2010).
• Behavioural testing: in visual reinforcement audiometry the reinforcer is placed within the child’s functional visual field, taking coloboma and field loss into account. Motor delay can slow the head turn, so a longer response window is allowed.
• Vestibular tests: caloric testing, rotary chair, the video head impulse test (vHIT) and vestibular evoked myogenic potentials (VEMP) assess canal and otolith function separately; canal responses are absent in children with canal anomalies (Abadie et al., 2000).
• Imaging: temporal bone CT shows the ossicles, oval and round windows, semicircular canals and the course of the facial nerve; MRI shows the cochlear and vestibular nerves in the internal auditory canal. The guideline recommends assessing cranial and auditory anatomy completely in a single anaesthetic session where possible (de Geus et al., 2017).

Imaging is decisive in cochlear implant candidacy. In a series of 13 patients from one implant centre, CT showed semicircular canal aplasia in 92%, oval window atresia in 77% and an aberrant course of the facial nerve or emissary veins in 46%, while MRI showed vestibulocochlear nerve aplasia in five patients (Arndt et al., 2010). The differential diagnosis includes other inner ear malformations, auditory neuropathy spectrum disorder (ANSD) and causes of bilateral vestibulopathy without canal anomalies.

Treatment and audiological rehabilitation

Care is planned by a multidisciplinary team, and airway, cardiac and feeding problems take priority in the first months. Early auditory habilitation is recommended, and amplification should start as soon as hearing loss is identified (van Ravenswaaij-Arts et al., 2025). Soft, misshapen pinnae can make it hard to keep a behind-the-ear aid in place, so retention accessories or bone conduction devices on a softband may be needed. Bone conduction implants are an option when the middle ear is abnormal but the cochlear nerve is intact, and a remote microphone system is recommended at school age (van Ravenswaaij-Arts et al., 2025). The decision on ventilation tubes for persistent otitis media with effusion rests with the ENT surgeon.

A cochlear implant is considered for bilateral severe to profound sensorineural loss. Surgery is challenging because of semicircular canal aplasia, window atresia and an aberrant facial nerve; the tympanic segment of the facial nerve has been reported to run over the promontory in 19% of ears and over the round window in 9.5% (Choo et al., 2017). Outcomes vary widely. In one series, responsiveness to sound improved in most implanted patients, but none of the patients with CHARGE reached open-set speech understanding and some continued to rely on sign language; the authors attributed this to the duration of auditory deprivation, late implantation and coexisting developmental difficulties (Arndt et al., 2010). A cochlear nerve at least as thick as the facial nerve on MRI and the absence of severe cognitive delay have been linked with better results, and a few patients who did not benefit from an implant have received an auditory brainstem implant (Choo et al., 2017). A systematic review of 165 implants in 156 patients from 31 studies found audiological outcomes too heterogeneous to pool, noted that cochlear nerve deficiency, inner ear anomalies and developmental delay may affect results and that complications are more frequent because of abnormal anatomy, and recommended case-by-case multidisciplinary assessment (Amin et al., 2019).

Children with vestibular areflexia learn to balance using vision and proprioception (Choo et al., 2017); because visual loss weakens this sensory substitution, physiotherapy and early intervention for motor development are important. No single communication method fits every child: spoken language, sign language, tactile signs and object or picture symbols can be combined according to hearing and vision, and referral to services experienced in deafblindness is recommended (van Ravenswaaij-Arts et al., 2025). In a study based on parental reports, 39% of the children (11 of 28) did not use symbolic language; successful management of hearing loss with amplification, independent walking and communication training started before age 3 were associated with symbolic language (Thelin and Fussner, 2005).

Impact on quality of life and advice

Children with CHARGE spend their early years with frequent operations, hospital admissions and feeding difficulties, and the combination of hearing, visual and balance problems affects every area of development. Behavioural features such as repetitive behaviours, anxiety and sudden outbursts are often reported and are frequently linked to communication difficulty, pain or sensory overload (van Ravenswaaij-Arts et al., 2025). These behaviours should not be read simply as a measure of cognitive ability; once hearing and vision are addressed, a child’s potential can be judged more accurately.

Practical advice: aim for your child to wear hearing aids during all waking hours, and if they keep coming off, try retention accessories with your audiologist. When talking, make sure your face is well lit and within the area your child can see, and use signs supported by touch and objects. Do not interpret motor delay as laziness or unwillingness; give your child chances to move on safe surfaces. Talk to the team about combining procedures that need anaesthesia or imaging. At school, ask for adjustments to lighting, seating and classroom acoustics and for a remote microphone system. Hearing and vision checks should continue into adulthood.