Introduction 

Klippel-Feil syndrome (KFS) is a rare congenital condition that typically presents during early infancy. It is observed through physical signs and is caused by the fusion of two or more cervical vertebrae, such as a short neck or limited neck movement. Later diagnosis can occur during an individual's teen years or during adulthood. For instance, individuals may notice neck pain, hearing loss or any neurological symptoms.¹ 

This syndrome can be caused by mutations in GDF6, GDF3, and MEOX1. Furthermore, alongside the fusion of cervical vertebrae, other organ systems can be implicated, including auditory pathways. For instance, hearing loss in KFS can be either conductive or sensorineural.²

Overview of Klippel-Feil syndrome

KFS is not caused by genetic factors or family history, but primarily due to mutations in the genes, specifically during fetal development, which can affect the development of the bone and spine. The syndrome occurs during early infancy and progresses later in life.¹ Other syndromes that can be associated with KFS may include Goldenhar, CHARGE or Wildervanck.³ 

Typical symptoms and physical characteristics that can be noticed include a short neck or limited neck mobility.⁴ The symptoms and the complications of the syndrome spread from severe to multisystemic. This can be skeletal, cardiac, renal or auditory.⁵ Furthermore, there are audiological associations to the syndrome, which is the primary cause of symptoms involving hearing loss. This is due to the embryological link with the development of the cervical spine, skull base and the auditory structures. 

Types of hearing loss in KFS 

It is known that there is around a 30–50% prevalence of KFS patients with hearing loss. It usually depends on the area of the auditory system that it affects.⁵ 

Conductive hearing loss (CHL)

The cause of conductive hearing loss is usually due to sound being blocked or not conducted properly due to abnormalities in the outer/middle ear.⁶ There are three common abnormalities in KFS: 

• Malformed ossicles
• External auditory canal atresia 
• Eustachian tube dysfunction

Hearing loss can vary from mild to moderate. Treatments can include ventilation tubes or ossiculoplasty.

Sensorineural hearing loss (SNHL)

The cause of SNHL involves the cochlea or auditory nerves, which are usually damaged or maldeveloped.³ It is usually associated with inner ear malformations such as:

• Mondini dysplasia 
• Cochlear hypoplasia
• Vestibular anomalies 

It is related to the damage in the neural crest cell migration, which contributes to both spinal and auditory structure development.⁷ It is irreversible and permanent. 

Mixed hearing loss

A presentation of both conductive and sensorineural characteristics in the same ear. It is due to both middle ear (ossicular malformation, infections) and inner ear (cochlear or nerve defects).

Pathophysiology and anatomical abnormalities

Embryological basis

Originates in the cervical vertebrae from somites derived from paraxial mesoderm. The middle and inner ear structures and the skull base originate from pharyngeal arches, otic placode and neural crest cells.⁸ 

Mistakes in these neural crest migrations or mesodermal differentiations can result in multiple adjacent systems. Therefore, they can cause cervical spine fusion, middle and inner ear problems or cranial nerve abnormalities.

Middle ear abnormalities (CHL):⁶

• Ossicular chain malformations – Abnormal shapes and sizes 
• Stapes fixation – Limits transmission of sound vibrations to the oval window. Can mimic otosclerosis in audiological profiles
• Tympanic membrane anomalies – Thin, retracted, or malpositioned 
• Eustachian tube dysfunction: Chronic otitis media can be caused due to this dysfunction

Inner ear and neural involvement (SNHL)

Cochlear hypoplasia is an underdeveloped or malformed cochlea, which can result in partial or profound SNHL. Mondini malformation is incomplete cochlear partitioning, which can be associated with vestibular abnormalities or abnormal cranial nerve VIII development.⁹

Temporal bone CT/MRI findings

Help to evaluate the ossicular chain, middle ear space, and external auditory canal by identifying bony atresia, ossicle dysplasia or fixation.¹⁰ 

Clinical presentation and diagnosis

Clinical signs and symptoms

• Delayed speech/language development is one of the early symptoms. It can cause severe hearing loss
• Poor school performance or inattentiveness is usually moderate hearing loss and can be a little more difficult to detect. Individuals may mimic ADHD or learning disorders, making diagnosis difficult¹¹

Audiological evaluation

• Pure tone audiometry is a standard test for children and adults to help distinguish between CHL, SNHL and mixed hearing loss
• Tympanometry is a test that evaluates the middle ear status
• Auditory brainstem response (ABR) for infants or uncooperative patients helps to look into the brain function¹¹

Imaging

• CT scan: Ossicular chain and middle ear evaluation
• MRI: Inner ear and auditory nerve integrity¹²

Differential diagnosis

Distinguishing KFS-related hearing loss from syndromic or acquired causes.¹³

• CHARGE syndrome 
• Wildervanck syndrome
• Recurrent otitis media
• Treacher Collins syndrome
• Otosclerosis
• Congenital CMV infection

Management and treatment strategies

Multidisciplinary approach¹⁴

• ENT specialists
• Audiologists 
• Geneticists
• Speech therapists
• Neurologists.

Hearing aids and amplification¹⁵

Air or bone conduction hearing aids are useful for mild to moderate CHL or SNHL. They fit behind the ear or in the canal and are used for the function of the tympanic membrane.  Bone conduction hearing aids can be used when the external auditory canal is atretic or malformed. They transmit vibrations to the inner ear through the skull.

Surgical interventions¹⁶

• Tympanoplasty or ossiculoplasty for CHL
• Cochlear implants in severe SNHL cases

Speech and language therapy³

This therapy works to help an individual express and present language development by improving speech clarity and preventing auditory discrimination. It can be helpful in social settings. Early intervention aids with language development and cognitive outcomes.

Educational support⁵

Helps to spread awareness and helps with communication and learning. Individuals can be encouraged to consistently use hearing devices with people around who are also knowledgeable about the device. 

Prognosis and quality of life considerations

Long-term outcomes 

Early diagnosis plays a crucial role in the long-term effects. If diagnosed during infancy and early childhood, speech and language can be improved and present better results due to early treatments and therapy. Furthermore, it will be easier for children to work in an educational environment as treatments will be tailored to their needs. Patients with inner ear malformations experience worse sensorineural hearing loss over time. Regular audiological monitoring can help identify changes early.¹⁷

Psychosocial impacts 

Communication in social settings can be impacted, and this can result in withdrawal and slow growth. It can also cause bullying, low self-esteem and behavioural problems. As a result, family and caregivers may experience stress, and individuals may even struggle in academic settings.¹⁸

Importance of early intervention 

Enhances speech by making pronunciations more articulate. It can also improve an individual's cognitive development. Furthermore, academic performance such as writing, reading and comprehension can also improve.¹⁹ 

Current research and future directions 

To further research KFS, the understanding of genetic and embryological mechanisms should be studied further. For instance, the molecular pathways involved in KFS and auditory development. The genes specifically GDF6, GDF3, and MEOX1 should be identified with any other gene mutations that may cause this syndrome.²⁰ 

Technology improvements in high-resolution imaging and cochlear implant programming are enhancing diagnostic precision and auditory outcomes. However, there is a gap in the knowledge of longitudinal studies, particularly with examinations of hearing loss in KFS. Larger-scale studies on hearing outcomes in KFS patients are required. However, personalised medicines can help with gene-targeted therapies.²¹

Summary

KFS is a rare congenital syndrome which presents with multisystem involvement, such as hearing impairment. It can be either conductive or sensorineural hearing loss or mixed. Symptoms can be severe or mild; however, they can affect an individual’s social behaviour and lead to complications in academic settings and social environments.²² 

To prevent symptoms and manage them, early diagnosis is beneficial. Exams and scans can help to identify and enable appropriate therapy and tailored treatments to be provided. This can help with speech development, academic achievement, and social participation.

FAQs

What is Klippel-Feil syndrome (KFS)?

It is a rare congenital syndrome that results in a short neck, limited neck movements and hearing loss.

How common is hearing loss in KFS patients?

30–50% individuals 

What types of hearing loss are associated with KFS?

• Conductive hearing loss
• Sensorineural hearing loss 
• Mixed hearing loss

How is hearing loss in KFS diagnosed?

• Audiological tests 
• Imaging studies 

Is hearing loss in KFS permanent?

In KFS, only sensorineural hearing loss is permanent. 

How does hearing loss affect daily life and development?

It affects an individual’s:

• Speech 
• Language 
• Academic performance 
• Social interactions