For most of us, hearing happens without us thinking about it. However, for some, hearing can be a tricky thing, especially for people with Fraser Syndrome, where parts of the ear don’t always work as they should. These changes can make hearing more challenging, but understanding the cause of it might make things feel less scary, and it is the first step in tackling these challenges. 

Keep on reading to learn about how differences in ear development in Fraser Syndrome affect hearing, and what this could mean for you!

Let’s dive in: what you need to know about fraser syndrome

What is fraser syndrome? 

Fraser Syndrome, also known as Branchio-oto-renal Syndrome (BOR), is a rare genetic disorder presenting developmental abnormalities in various organs and body parts. Some of the default characteristics of the disease are eyes covered with skin (cryptophthalmos), fused skin between fingers and toes (syndactyly), as well as abnormalities in the genitalia and urinary tract (genitourinary anomalies). Less frequently, some people can experience abnormalities in nose and ear formation, respiratory tract issues, cleft palate, skeletal problems, and kidney development failure.¹ These symptoms that present themselves during pregnancy or birth are due to genetic changes in three genes: FRAS1, GRIP1, and FREM2. The severity of the symptoms determines the fatality of Fraser’s Syndrome, and less severely affected individuals tend to survive into childhood and adulthood. ²

Fraser syndrome and hearing loss

In his 1980 study, Dr. Fraser identified that 1 in 200 children with Fraser Syndrome experience severe hearing loss.¹² Later clinical studies certified hearing abnormalities as a well-established pathology of Fraser Syndrome, with 89% of patients presenting varying degrees of hearing loss.¹⁸

As you’ll see in the following parts of this article, hearing loss in Fraser Syndrome can be due to several different developmental problems affecting the structures of the ear. It is important to understand the causes of hearing loss to better tackle the situation at hand. 

In this article, we will discover how changes in the external, middle, and inner ear can lead to hearing loss. 

How fraser syndrome can change the shape of the outer ear

What we often see

Congenital abnormalities can affect the external, middle, and inner ear. The more common external ear anomalies vary in severity. Microtia is when the outer ear is not fully developed, appearing smaller. Doctors classify the severity of the condition under four grading systems, with the least severe Type One corresponding to a smaller ear with all parts present and the most severe Type Four corresponding to the absence of any structures of the external ear.  Depending on the severity of Microtia, individuals can experience varying levels of hearing loss. In addition to microtia low low-set ears, and a malformed structure of the outer ear are evident in people with Fraser Syndrome. ¹⁹

Small bones but a big impact on hearing: middle ear changes that can cause hearing loss

The role of ossicles in hearing loss

The middle ear houses three small bones called ossicles (malleus, incus, stapes). In Fraser Syndrome, the development of these bones can be affected in a variety of ways, leading to hearing abnormalities. Isolated ossicular abnormalities are classified under four groups, each characterised by different affected structures. Class I is stapedial ankylosis, where the stapes bone in the middle ear is fused to the surrounding tissue. In Class II, stapedial ankylosis is present alongside other ossicular anomalies such as abnormalities in the two other ossicular bones, the malleus and incus. Class III is characterised by ossicular abnormalities that don’t involve stapedial ankylosis. The last class, Class IV, refers to the malformations of the oval/round window in the middle ear. The oval window’s structure is important for the sound waves to be transmitted to the eardrum, as it is where the stapes bone sits and connects to the inner ear. People with these ossicular malformations can experience differing degrees of conductive hearing loss, since the vibrations won’t be properly transferred from the eardrum. ^4,5

While problems with the ear bones themselves can cause hearing loss, issues elsewhere in the head, like a cleft palate, can also interfere with how the ear works.

How a cleft palate can affect the ears

As we’ve discussed before, with Fraser Syndrome, cleft palate can be one of the developmental issues patients can experience. A cleft palate happens when the upper lip and the roof of the mouth (palate) don’t close up fully during pregnancy, leaving a gap/cleft.⁶ In people with cleft palates, the muscles that control swallowing and speech (palatal muscles) are underdeveloped, which in turn can negatively affect the eustachian tube function.⁷ Eustachian tube is a narrow, cylindrical passage made out of bone and cartilage that connects the middle ear to the back of the throat. It plays a crucial role in regulating the air pressure in the ear, as well as protects the middle ear from infections by draining fluid from the ear.⁸ When the function of the eustachian tube is impeded, it cannot drain fluids. This causes the middle ear to become filled with secretions from the ear, leading to a phenomenon called “Glue ear”. Due to the fluid built up, the bones in the middle ear cannot vibrate as freely. Additionally, the sound waves travel more slowly in the fluid. In combination, these issues lead to hearing loss.⁷

Changes to the ear’s hearing centre: structural differences in the inner ear

As you move from the external ear inward anatomically, the inner ear sits next to the middle ear. It houses the cochlea, semicircular canals, otolith organs, as well as the vestibular and cochlear nerves, which are responsible for balance and hearing, respectively. The cochlea is involved in hearing, while the semicircular canals and otolith organs are involved in balance. Although less common than external and middle ear abnormalities, inner ear problems can occur in people with Fraser Syndrome, leading to hearing loss.⁹ The inner ear abnormalities can be classified under different cochlear malformations, as well as problems with the neurons involved in hearing. Before we discuss cochlear malformations, it might be beneficial to understand the anatomy of the cochlea. Cochlea sits in the bony labyrinth of the inner ear, and is a spiral-shaped, fluid-filled (endolymph) organ that houses tiny hair cells within a special structure called the organ of Corti. This allows sound waves to be amplified and turned into electrical signals that the neurons can pick up.¹⁰ The cochlear malformations range from a fully absent cochlea to varying degrees of size and structure abnormalities.¹¹ These differential developments can lead to sensorineural hearing loss. Other factors that might cause sensorineural hearing loss are pathologies in the auditory nerve (cochlear nerve) and the central nervous system.

How common is it: should I be worried about hearing loss in fraser syndrome?

In Dr. F.C. Fraser’s 1980 paper, the study from which the disease gets its name, it was identified that among the patients experiencing hearing loss 30% showed conductive, and 20% showed sensorineural hearing loss, while 50% presented with a mixed type. While the conductive hearing loss is due to abnormalities in the external and middle ear, the sensorineural hearing loss is mainly due to abnormalities in the inner ear. The clinical presentation and the severity of hearing loss vary among individuals. For some patients, the hearing loss might be present at birth and stay consistent throughout the lifetime, while for some it can show up later or get progressively worse over time.¹²

As you can imagine, hearing impairments can affect the patient's speech and language development greatly. It has been shown that children with hearing impairments have a lower speed of learning when it comes to new words, have problems in speaking clearly and understanding others due to not hearing well, as well as struggling in school.¹³

Getting a clear picture of hearing health: different diagnostic assessments

Physical examination

The first evaluation that can be done to diagnose hearing loss and its cause is otoscopy. Otoscopy is the inspection of the structures of the external ear and the eardrum visually using an otoscope. Through this examination, any abnormalities in the external ear structures can be identified.¹⁴

Audiological assessment

The next step in diagnosing hearing loss will give a more certain answer is to perform some audiological assessments. Newborn hearing screening is a service offered to every newborn that can identify any congenital hearing loss. The newborn hearing screening involves recording the response the newborn has to the clicking sound placed from an earpiece.  Later in life, audiometry assessments can be performed.¹⁵ Audiometry assessments involve three different tests: the mechanical sound transmission test for assessing middle ear function, the neural sound transmission test for assessing cochlear and neural function, and the speech discrimination ability test for assessing patients' hearing and understanding of speech. These different assessment methods can not only diagnose the degree of hearing loss but also help identify the type of hearing loss (conductive, sensorineural, mixed).¹⁶

Imaging

In some cases, physical and audiological assessments might not be enough to identify the cause of hearing loss. For those situations, imaging techniques like high-resolution computed tomography (CT) or magnetic resonance imaging (MRI) could be used to look at temporal bones, assess the ossicle structures of the middle ear, and inner ear structures such as the cochlea.¹⁷

Summary

For people with Fraser Syndrome, among other symptoms, hearing loss due to developmental abnormalities in the external, middle, and inner ear is a common problem. They can experience varying degrees of hearing loss, and it can be present at birth and/or get progressively worse as they age. The type of hearing loss they experience can be different, conductive or sensorineural; however, more than 50% of patients experience a mixed version. Underdeveloped outer ear (microtia) and malformed middle ear bones (isolated ossicular abnormalities) can lead to conductive hearing loss. On the other hand, a malformed cochlea and abnormalities in the auditory nerve can lead to sensorineural hearing loss. 

Hearing loss can affect speech development and learning in children; hence, early diagnosis is very important. There are several ways that hearing loss can be diagnosed. Physical exams of the external ear and eardrum, newborn auditory screenings, audiometry tests, and imaging of ear structures using CT or MRI can all be ways to identify hearing loss and the root cause. 

Knowing how Fraser Syndrome affects hearing helps patients and their families understand what’s happening and take steps to manage these challenges.