Ear Anomalies in Charge Syndrome - An Overview

What Is Charge Syndrome?

CHARGE syndrome is a condition that impacts various parts of the body. The name CHARGE stands for the common features of the disorder: coloboma (an eye defect), heart defects, atresia choanae (a blockage in the nasal passage), growth retardation, genital abnormalities, and ear abnormalities. The pattern of issues differs from person to person. These health problems due to the syndrome can be severe, especially during the infancy period. People with CHARGE syndrome usually have several or a mix of primary and minor features. CHARGE syndrome affects about 1 in 8,500 to 10,000 newborns.

What Causes Charge Syndrome?

Most cases of CHARGE syndrome are diagnosed based on clinical criteria. These criteria are caused by mutations in the CHD7 (chromodomain helicase DNA binding protein 7) gene, which occur spontaneously (not inherited) in over 90 percent of cases. Occasionally, the syndrome can be inherited from a parent in an autosomal dominant pattern.

This gene generates a protein that aids in controlling the activity of genes throughout the developmental process. Mutations in this gene result in shorter or defective CHD7 protein. Hence, the development of neural crest cells is impacted, and normal gene regulation is upset. These alterations cause many symptoms associated with CHARGE syndrome, particularly if they occur before birth.

What Are the Ear Anomalies Seen in Charge Syndrome?

About 90 to 100 percent of patients with CHARGE syndrome symptoms have external ear malformations. Charge syndrome ears may be small, simple, low-set, cup-shaped, or unraveled helix. These malformations are often worse on the side with facial palsy. The reason behind them is early nerve issues during ear development.

Charge Syndrome Ear Abnormalities -

The various diagnostic findings observed in different parts of the ear are mentioned below:

• Outer and Middle Ears: CHARGE syndrome's outer and middle ears primarily affect how sound is conducted to the inner ear. Conductive hearing loss is common, where the sound reaching the inner ear is softer due to issues in the outer or middle ear structures.

• Outer Ear (Pinna): The shape of the outer ear (pinna) in CHARGE syndrome can be noticeably different, potentially affecting the use of behind-the-ear hearing aids. Surgical intervention may sometimes improve the shape to accommodate hearing aids better.

• Ear Canal (External Auditory Canal): Ear canals in CHARGE syndrome may be narrow (stenotic), complicating ear examinations, cleaning, and fitting of hearing aids. Complete absence (atresia) of the ear canal causes significant conductive hearing loss. Such cases sometimes require surgical construction.

• Middle Ear: The middle ear includes the eardrum and ossicles, which transmit sound vibrations to the inner ear. Malformed ossicles contribute to significant conductive hearing loss in CHARGE syndrome. This type of hearing loss particularly affects low-frequency sounds. Surgical correction is usually not attempted.

• Inner Ear (Cochlea): Abnormalities in the inner ear or cochlea cause permanent hearing loss in CHARGE syndrome. Sensorineural hearing loss, resulting from damage to the cochlea or auditory nerves, may require amplification to hear sounds clearly, though it can distort speech and other sounds. These conditions require careful management and often involve surgical interventions like pressure-equalization tubes (PE tubes) to alleviate middle ear issues and temporarily improve hearing.

Hearing Loss Associated With Charge Syndrome -

Hearing loss in CHARGE syndrome affects 60 to 90 percent of individuals. It is usually seen in both ears and with different types of impairment. Inner ear issues like Mondini malformation or incomplete development of semicircular canals lead to nerve-related deafness. Problems in the middle ear cause hearing loss due to bone or tendon abnormalities or fluid buildup. CT scans show these abnormalities, such as underdeveloped semicircular canals.

How Can Charge Syndrome Be Diagnosed?

A medical geneticist or another specialist familiar with CHARGE syndrome should conduct a comprehensive physical examination. They will also order tests to identify the syndrome's major and minor features.

Molecular genetic testing can detect variants in the CHD7 gene associated with the condition. A chromosomal microarray (SNP) should be performed if no disease-causing variants are found. In this test, some patients may have submicroscopic changes in the chromosome 8q12.2 region. If both tests yield normal results, whole-genome or exome sequencing should be considered. This approach is necessary because other genetic disorders share clinical features with CHARGE syndrome. Also, in cases where new variants in genes like ZEB2, KMT2D, and EFTUD2 have been identified in children previously diagnosed with CHARGE syndrome.

How Is Hearing Assessment Conducted in Charge Syndrome With Ear Anomalies?

The following are the two main tests commonly performed for patients with ear abnormalities:

1. Pure-Tone Audiogram -

• This test measures hearing thresholds at specific frequencies for each ear separately.

• Results are recorded on an audiogram.

• Tests involve responding to sound or using auditory brainstem response (ABR) for sleeping or sedated individuals.

• Frequencies typically tested are crucial for speech understanding (500, 1000, 2000 Hz, sometimes 4000 Hz).

• Essential for diagnosing ear problems and deciding on hearing aids.

• Testing should be repeated for accurate hearing threshold determination.

2. Tympanometry -

• Assesses eardrum and middle ear mobility.

• Requires the child to sit still briefly.

• Detects Eustachian tube dysfunction and middle ear fluid.

• Regularly used to manage middle-ear diseases but does not test hearing.

• Provides information specific to the middle ear's condition, not overall hearing ability.

How Does Charge Syndrome Differ From Other Syndromes?

CHARGE syndrome is distinct from other syndromes because it affects multiple cranial nerves, resulting in ENT (ear, nose, and throat) issues related to nerves such as the vagus, facial, glossopharyngeal, and olfactory. It frequently involves disorders like TE (tracheoesophageal) fistulas, cleft lip or palate, and choanal stenosis or atresia. The management of these complexities requires the early involvement of an ENT consultant.

In over 75 percent of cases, the syndrome also comprises dual sensory loss, which affects conventional hearing rehabilitation techniques that depend on clear vision. These kids' intelligence is frequently undervalued. Early detection of visual and hearing impairments is essential. Effective communication is necessary to improve quality of life and adequately measure intelligence.

How Are Charge Syndrome Ear Abnormalities Treated?

The audiologist must choose and fit hearing aids after the hearing has been properly measured. The only objective of hearing aids is to enhance hearing; if this objective is not met, the aids are of minimal use. This is the aim, but it is tough to accomplish in children with CHARGE syndrome ears. The ear molds should not cause pain or irritation to the child's ear canals. The hearing aids should remain affixed to the head, provide sufficient amplification without overwhelming the child, and enhance speech comprehension using amplified frequencies.

Besides hearing aids, there are assistive listening devices or auditory trainers. These gadgets have a microphone near the speaker to help listeners hear better, especially in noisy environments.

Specific considerations for CHARGE syndrome ear during treatment -

The choice of hearing aids depends on many factors.

• In-the-Ear (ITE) Aids: This type is usually unsuitable for children.

• Behind-the-Ear (BTE) Aids: These types are often preferred because they are powerful and flexible.

• Body-worn aids are also an option for severe hearing loss.

• Cochlear implants (surgically implanted devices) that stimulate nerves directly are considered only for severe to profound hearing loss.

• If hearing aids provide some benefit, cochlear implants are usually not recommended.

Earpieces must be regularly adjusted due to initially small ear canals and insufficient ear cartilage to support hearing aids. Cochlear implants have been successfully used in patients with CHARGE syndrome ear abnormalities. Children undergoing cochlear implantation for CHARGE syndrome should also receive training in sign language alongside speech communication training.

Conclusion:

Ear problems in CHARGE syndrome are complicated and affect hearing and balance. Early diagnosis and a team approach to treatment are crucial for improving outcomes. Progress in genetics and hearing technology is aiding in better understanding and treating these issues. It also provides hope for a better life for people with CHARGE syndrome.