DFNB1: A Look at This Common Genetic Hearing Loss

DFNB1, which stands for “Deafness, Autosomal Recessive 1,” is the most frequent cause of inherited hearing loss present from birth. It is a non-syndromic hearing impairment, meaning the condition is isolated to the ears and not associated with other medical problems. Understanding DFNB1 provides insight into a condition that affects approximately 1 in every 2,500 children.

The hearing loss is a direct result of genetic changes that disrupt the normal function of the inner ear. The discovery of its genetic roots has improved the ability to provide early and accurate diagnoses for newborns and their families. This allows for timely counseling and educational planning.

The Genetic Cause

The cause of DFNB1 is a gene known as GJB2, located on chromosome 13. Genes act as instructions that tell cells how to make proteins, which perform a vast array of tasks. The GJB2 gene holds the blueprint for a protein that is necessary for the function of the inner ear.

DFNB1 is inherited in an autosomal recessive pattern. This means a child must inherit two mutated copies of the GJB2 gene—one from each parent—to have the condition. The parents are typically “carriers,” with one mutated and one standard copy of the gene, which is not enough to cause hearing loss.

When both parents are carriers of a GJB2 mutation, there is a 25% chance with each pregnancy that the child will be affected by DFNB1. There is a 50% chance the child will be a carrier, and a 25% chance the child will inherit two standard copies. The prevalence of carriers for GJB2 mutations is high in certain populations, which contributes to DFNB1 being a common form of congenital deafness. For example, the c.35delG mutation is the most common in Caucasian populations.

How Hearing is Affected

Hearing loss in DFNB1 occurs because of a disruption in the cochlea. The GJB2 gene contains instructions for producing a protein called connexin 26. This protein is a building block for cellular channels known as gap junctions, which form pores connecting adjacent supporting cells.

These gap junctions recycle potassium ions. During the process of hearing, sound vibrations cause sensory hair cells in the cochlea to activate. This activation involves the movement of potassium ions. For the hair cells to remain sensitive and ready to respond to new sounds, this potassium must be efficiently cleared away and returned to a fluid-filled compartment of the cochlea called the endolymph.

The network of gap junctions creates a pathway for this potassium recycling. When mutations in the GJB2 gene prevent the production of functional connexin 26, these channels cannot work properly. The failure of this system leads to a toxic buildup of potassium around the hair cells, causing them to malfunction and perish. Without healthy hair cells to convert sound into neural signals, hearing is impaired.

Clinical Diagnosis and Characteristics

The first indication of DFNB1 is often a failed newborn hearing screening. These routine tests, often using methods like otoacoustic emissions (OAE) or automated auditory brainstem response (AABR), are designed to detect potential hearing issues in the first days of life. A “refer” result on a screening does not diagnose hearing loss but signals the need for more comprehensive audiological testing with a specialist.

This follow-up evaluation confirms the hearing loss, and genetic testing is often recommended to determine the underlying cause. A blood sample is analyzed for mutations in the GJB2 gene and sometimes the nearby GJB6 gene. A confirmed genetic diagnosis provides families with definitive answers and helps guide future management.

The hearing loss associated with DFNB1 has several defining characteristics:

• It is congenital (present at birth) and typically affects both ears.
• The severity can range from moderate to profound, even among siblings with the same mutations.
• The hearing loss is generally non-progressive, meaning it does not worsen over time.
• It is non-syndromic, so individuals do not have related medical issues with other body systems.

Intervention and Management

Once a diagnosis is confirmed, intervention focuses on supporting the child’s auditory and language development. For children with moderate to severe hearing loss, hearing aids are often the first step. These devices amplify sound, making it accessible to the child’s remaining functional hair cells.

For individuals with severe to profound hearing loss where hearing aids may not provide sufficient benefit, cochlear implants are an effective option. A cochlear implant is a medical device that bypasses the damaged hair cells in the cochlea. It directly stimulates the auditory nerve with electrical signals, which the brain interprets as sound.

In addition to technology, early intervention is a part of management. This involves a team of professionals providing support tailored to the child and family. Speech-language therapy helps develop spoken language and communication skills. Families are also introduced to various communication methodologies, allowing them to make informed choices that best suit their child. The combination of appropriate technology and early support helps children with DFNB1 to develop language and thrive.