Introduction

Nager syndrome is a developmental disorder, with most cases suspected to occur due to a mutation in the SF3B4 gene. This particular genetic alteration leads to abnormal cell growth and malformations of the skeletal system. In particular, Nager syndrome is characterised by abnormalities in the skull, facial bones, and limbs.¹

This article aims to provide a comprehensive overview of Nager syndrome, with a particular focus on the abnormalities of the ear and the subsequent hearing impairments that individuals who suffer from this condition may present with.

Nager syndrome: background

Nager syndrome was the first recorded condition to fall under the category of acrofacial dysostoses (AFDs), which are a group of rare disorders that involve the malformation of various skeletal structures, including the limbs.¹

Although the exact prevalence of Nager syndrome is unknown, it is estimated that globally there are between 200 and 300 documented cases, making it a very uncommon condition. The majority of these cases are caused by sporadic mutations (i.e., there is no familial history of the disease), but there have also been incidences of inherited mutations.

The severity of Nager syndrome can vary significantly amongst individuals. Despite there being no cure for this condition, individuals with Nager syndrome can typically have a normal life span. However, this is often accompanied by surgeries to manage structural abnormalities that may arise due to the disorder.¹

Common abnormalities and related systemic problems associated with Nager syndrome include:

• Malformed or absent thumbs—this anomaly can cause problems with grip and fine motor movement
• Underdevelopment of cheekbones (malar hypoplasia)—this can affect facial symmetry and function
• Underdevelopment of the lower jaw (mandibular hypoplasia) leads to micrognathia (i.e., an undersized jaw)—this usually obstructs part of the airway, and therefore, can lead to life-threatening breathing problems without corrective surgery
• An opening in the roof of the mouth (cleft palate) can cause feeding problems in infants
• Small and/or malformed external ears, often accompanied by absent external ear canals, lead to various hearing impairments and perhaps delayed speech development

This overview provides an insight into the complexities of Nager syndrome, and how an individual can be affected in different ways that deviate away from typical bodily function.

This article will now go on to conduct a more detailed examination of the different ear abnormalities and hearing impairments associated with the syndrome.

Hearing loss in Nager syndrome

Small and/or abnormally formed ears are a developmental issue of Nager syndrome, and hearing loss/impairments arise in almost half of confirmed Nager syndrome cases.² There are different ear malformations that can impair hearing in Nager syndrome.

Ear abnormalities in Nager syndrome

External ear

• Microtia refers to small or malformed outer ears. In severe cases, the whole external ear may be missing
• Abnormal external ear canal formation (stenosis or atresia)—ear canal stenosis is a narrow ear canal, where aural atresia refers to a missing external ear canal

Middle ear

• Abnormalities in the ossicular chain—three bones (the malleus, incus, and stapes)joined by two synovial joints in the middle ear, responsible for primary sound conduction—disrupt ear function ³
• Abnormalities in the tympanic membrane (eardrum)—which separates the outer ear from the middle ear and vibrates when impacted by sound waves, which are then passed onto the ossicular chain—affect hearing ability⁴

Inner ear

The intricacies of inner ear abnormalities in individuals with Nager syndrome are less known. However, due to the types of hearing loss observed in Nager syndrome, it is suspected that inner ear dysfunction does occur.

The otic placode is a structure that forms early in development and helps make inner ear structures that assist with hearing and balance. People with Nager syndrome have altered or dysfunctional otic placodes, thereby causing hearing loss.³

Types of hearing impairments in Nager syndrome

Conductive hearing loss

Conductive hearing loss is associated with defects in the outer and/or middle ear, which makes it difficult for sound waves to reach the inner ear.

Conductive hearing loss is the most common type of hearing impairment observed in individuals with Nager syndrome.³ Approximately 60% of those with small or abnormally formed ears have defects which cause conductive hearing loss.

Sensorineural hearing loss

Sensorineural hearing loss occurs due to damage or dysfunction in the inner ear, which prevents the transduction of signals that transmit the sound information to the brain.⁵

Mixed hearing loss

The condition is a combination of both conductive and sensorineural hearing loss (i.e., damage or dysfunction in the outer or middle ear, and in the inner ear). 

Diagnosis and impact of hearing impairments

Diagnosis

Diagnosis of Nager syndrome will typically be established with a physical examination when the individual is newly born. Depending on how conclusive this examination is, genetic testing can be done to confirm the diagnosis.

There are several ways to diagnose a hearing impairment:

Newborn hearing screening

This standard test is conducted on all newborn babies in the UK. This screening ascertains if the inner ear of the baby is working normally. The implementation of this test is excellent for early detection of hearing impairment and to establish a treatment plan as soon as possible.

Hearing tests: audiometry and tympanometry

Audiometry is a comprehensive test that evaluates the function of the hearing mechanism in general, whereas tympanometry tests the specific functionality of the middle ear.⁶

Imaging studies

Advanced imaging techniques such as computed tomography (CT) scans and magnetic resonance imaging (MRI) can be used to identify the structural anomalies of the ear and surrounding areas that may not be visible to the eye.

Impact

Despite being a rare condition, the impact of Nager syndrome on individuals with the disorder is profound, with different aspects of life often being affected.

As mentioned earlier, speech and language development delays are not uncommon when dealing with hearing impairments in babies and children. Hearing loss can hinder a child’s ability to listen and comprehend spoken language, which is important for normal speech development.

While speech/language development is a more obvious effect of hearing loss or impairment, there are also downstream effects on social and educational skills. The impact of childhood hearing loss is often reflected in lower self-esteem, and underachievement at school.

In general, hearing impairments and other structural abnormalities due to Nager syndrome can be detrimental to the individuals with the syndrome if they do not receive care and support.

Management and treatment

Management of hearing impairments in Nager syndrome will often encompass multiple different treatment pathways, some of which are listed below.

Medical intervention

• Surgical reconstruction can improve the appearance of the outer ear that may be deformed or missing altogether
• Hearing aids and assistive devices—actual auditory support for hearing loss is mostly given via hearing aids
• Cochlear implants may be offered to the individual if a problem is identified with the inner ear

Therapeutic support

Therapeutic support services are also essential for people with Nager syndrome. Some examples of such support can be found below:

• Speech therapy shall assist in the development of communication skills
• Educational support: specialised and individualised educational assistance to address learning challenges
• Family counselling and support groups: emotional support given to the individuals and their families is important to help navigate this condition

Summary

Nager syndrome is clearly a complex condition with multiple facets affecting various aspects of life. The impact of Nager syndrome on hearing is profound, necessitating further research to fully comprehend the changes that occur and develop specific treatment. The advancement of genetic therapies or more effective surgical techniques could play a part in managing this condition.

Early detection of Nager syndrome can play a significant role in improving the quality of life for the individual, and prompt intervention can then be evaluated. Effective management involves a combination of medical and therapeutic support that should be individualised and become more robust in improving hearing loss completely.