Pendred syndrome

Overview

Pendred syndrome is a rare genetic disorder characterized by congenital sensorineural hearing loss and thyroid dysfunction, specifically the development of a goiter (an enlarged thyroid gland). It is one of the most common forms of syndromic deafness and often goes undiagnosed due to its variable presentation. In addition to auditory and thyroid issues, individuals with Pendred syndrome may also exhibit abnormalities of the inner ear, such as an enlarged vestibular aqueduct (EVA) or Mondini malformation. These structural abnormalities contribute to progressive hearing loss, which may worsen over time or with minor head trauma. Although thyroid dysfunction is a hallmark feature, most individuals with Pendred syndrome maintain normal thyroid hormone levels.

Causes

Pendred syndrome is caused by mutations in the SLC26A4 gene, which encodes a protein known as pendrin. Pendrin plays a crucial role in transporting ions, particularly in the inner ear, thyroid gland, and kidneys. Mutations in this gene impair pendrin’s function, disrupting ion balance and fluid homeostasis, especially in the inner ear, leading to sensorineural hearing loss and thyroid abnormalities.

The condition is inherited in an autosomal recessive manner, meaning a person must inherit two copies of the mutated gene—one from each parent—to develop the syndrome. Carriers with only one copy typically do not exhibit symptoms but can pass the gene to their offspring.

Symptoms

The symptoms of Pendred syndrome can vary in severity and presentation. The most common and defining symptoms include:

Hearing Loss:

• Typically bilateral (affecting both ears) and sensorineural in nature

• Present at birth or during early childhood

• Often progressive and may fluctuate, especially after minor head injuries or barotrauma (e.g., air pressure changes)

• May be associated with balance issues due to inner ear involvement

Inner Ear Abnormalities:

• Enlarged vestibular aqueduct (EVA): Commonly found in imaging studies of affected individuals

• Mondini malformation: A cochlear abnormality where the cochlea is incompletely formed

Thyroid Abnormalities:

• Goiter development typically appears during adolescence or early adulthood

• Most individuals remain euthyroid (normal thyroid function), but some may develop hypothyroidism

• Goiter may be diffuse or nodular and often grows slowly

Unlike other syndromes that affect multiple organ systems, Pendred syndrome primarily impacts the auditory and endocrine systems.

Diagnosis

Diagnosing Pendred syndrome involves a combination of clinical evaluation, audiologic testing, imaging studies, and genetic analysis. A comprehensive approach helps differentiate it from non-syndromic hearing loss and other genetic syndromes.

• Hearing evaluation: Audiometry confirms bilateral sensorineural hearing loss

• Imaging studies: CT or MRI of the temporal bones to identify enlarged vestibular aqueducts or Mondini malformations

• Thyroid function tests: Measure levels of thyroid hormones (T3, T4) and thyroid-stimulating hormone (TSH); thyroid peroxidase antibodies may also be checked

• Perchlorate discharge test: Assesses iodine organification in the thyroid; once used for diagnosis but now rarely performed due to advances in genetic testing

• Genetic testing: Confirms mutations in the SLC26A4 gene, supporting a definitive diagnosis

• Family history: Helps identify potential carriers and assess inheritance patterns

Treatment

There is no cure for Pendred syndrome, but treatment focuses on managing hearing loss, monitoring thyroid health, and supporting overall well-being. A multidisciplinary approach is often required, involving audiologists, endocrinologists, geneticists, and otolaryngologists.

Management of Hearing Loss:

• Hearing aids: Beneficial for individuals with mild to moderate hearing loss

• Cochlear implants: May be considered for severe to profound hearing loss, especially when traditional hearing aids are ineffective

• Speech and language therapy: Especially important in children to support communication development

• Protective measures: Avoiding head trauma and pressure changes to prevent sudden hearing loss episodes

Thyroid Management:

• Regular thyroid monitoring: Annual or biannual thyroid function tests and ultrasound assessments

• Thyroid hormone replacement: Prescribed in cases of hypothyroidism

• Surgical intervention: Rarely required, but may be considered for very large or symptomatic goiters

Genetic Counseling:

• Advised for affected families to understand recurrence risks, carrier testing, and family planning options

Prognosis

The long-term outlook for individuals with Pendred syndrome is generally favorable with appropriate management. While hearing loss is permanent and often progressive, the use of hearing aids, cochlear implants, and speech therapy can significantly improve communication and quality of life. Thyroid enlargement is usually benign and manageable with regular monitoring. Hypothyroidism, if it occurs, is treatable with hormone replacement therapy.

Early diagnosis and a proactive care plan can help affected individuals lead full and productive lives. As genetic testing becomes more accessible, early detection and intervention are increasingly possible, improving outcomes for children born with this condition.