Pendred syndrome
Pendred syndrome (PS) is a genetic condition primarily characterized by bilateral, severe to profound sensorineural hearing loss, often accompanied by thyroid abnormalities such as goiter. It is linked to mutations in the SLC26A4 gene, which plays a critical role in transporting ions vital for the proper functioning of the inner ear and thyroid. The condition is inherited in an autosomal recessive pattern, meaning that a child must inherit a nonworking gene from both parents to be affected. Although the exact prevalence of PS is unknown, it affects individuals of all genders and ethnicities.
Symptoms typically manifest at birth or during early childhood, and more than half of those affected may show inner ear abnormalities, particularly enlarged vestibular aqueducts. Genetic testing can assist in diagnosis, although mutations are identified in only about half of affected individuals from families with multiple cases. While there is no cure for PS, early intervention with hearing aids or cochlear implants, alongside speech and language therapy, can significantly improve outcomes. Patients benefit from a multidisciplinary approach to care, including specialists in genetics, audiology, and endocrinology. Most individuals with PS maintain normal intelligence and life expectancy, highlighting the importance of supportive medical care and family counseling.
Pendred syndrome
Also known as: Autosomal recessive sensorineural hearing impairment and goiter; deafness with goiter; goiter-deafness syndrome; Pendred’s syndrome
Definition Pendred syndrome (PS), first described by English physician Vaughan Pendred in 1896, is a genetic condition caused by mutations in the SLC26A4 gene. PS is one of the most common forms of syndromic hearing loss, accounting for about 10 percent of all cases of hereditary hearing loss. PS is associated with developmental abnormalities of the inner ear and is characterized by enlarged vestibular aqueducts (EVA) and severe to profound sensorineural hearing loss that is evident at birth. Individuals with PS may also have cochlea malformations (Mondini dysplasia) and goiter (enlarged thyroid gland), which typically forms between late childhood and early adulthood.
Risk Factors
There are no reported factors associated with an increased risk for having a child with PS; it is diagnosed in both males and females and in all ethnicities. The exact prevalence for PS is unknown.
Etiology and Genetics
PS is associated with mutations in the SLC26A4 gene located on the long arm of chromosome 7 (7q21-34) and is inherited in an autosomal recessive manner, in which a condition has to be inherited by both parents. A person who has one working gene and one nonworking gene is referred to as a carrier. A carrier is unaffected by the condition. However, when two carriers of the same nonworking gene have children, they have a 25 percent chance of both passing on the nonworking gene and thus, of having a child affected with the condition. This is also a 75 percent chance with each pregnancy that the child will not have PS. If one parent has PS, the chance of having an affected child depends upon the carrier status of the other parent. If both parents have PS, every child born will also have PS. SLC26A4, a member of the solute carrier 26 gene family, codes for the protein pendrin. Pendrin is involved in the transport of chloride, iodide, and bicarbonate ions into and out of cells, which is important for the normal function of the inner ear and thyroid. Ion transport is disrupted when SLC26A4 mutations alter the function or structure of pendrin. Currently more than sixty mutations have been reported. Mutations in SLC26A4 are also associated with nonsyndromic enlarged vestibular aqueduct (DFNB4). DFNB4 is similar to PS, but thyroid abnormalities are not associated with it.
Genetic testing is available for individuals suspected of having PS. However only 50 percent of individuals from families where multiple people are affected have a mutation identified. Families with only one individual affected have approximately a 20 percent chance of gene detection. Therefore PS is likely a genetically heterogeneous condition (caused by more than one gene).
Symptoms
PS is characterized by bilateral, severe to profound sensorineural hearing loss. Although mild-to-moderate and progressive hearing loss has been reported, hearing loss is usually nonprogressive and congenital. Individuals with PS have inner ear abnormalities of the temporal bones. In fact, more than 60 percent of individuals have bilateral enlarged vestibular aqueducts (EVA). Approximately 75 percent of individuals have evidence of goiter on clinical examination. In approximately 40 percent the goiter develops in late childhood or early puberty and for 60 percent in early adult life. There is significant interfamilial and intrafamilial variability.
Screening and Diagnosis
A clinical diagnosis is given to individuals with sensorineural hearing loss, bilateral enlarged vestibular aqueducts, and either a goiter or an abnormal perchlorate discharge test (a test to determine if the thyroid is working properly). Molecular genetic testing is available clinically to confirm the diagnosis if PS is suspected, to clarify risks for family members, and for prenatal diagnosis. Population screening for PS is not available.
Treatment and Therapy
There is no cure for PS. However, benefits are gained from early detection and treatment with hearing aids or cochlear implants and speech and language therapy. EVA may cause increased intracranial pressure that can cause a decline in hearing; therefore activities such as weightlifting, contact sports, and scuba diving should be avoided, and head protection for activities such as bicycling should be encouraged. The abnormal thyroid function should be treated in the standard manner. For optimal care, patients should see a variety of specialists, including a clinical geneticist, genetic counselors, otolaryngologists, audiologists, speech-language pathologists, and an endocrinologist.
Prevention and Outcomes
Genetic counseling should be made available for individuals with personal or family histories. Prenatal or preimplantation genetic diagnosis is available if the cause is known. Most individuals with PS have normal intelligence and life expectancies.
Bibliography
Kochhar, A., M. S. Hildebrand, and R. J. H. Smith. “Clinical Aspects of Hereditary Hearing Loss.” Genetics in Medicine 9 (2007): 393–409. Print.
Kontorinis, Georgios, et al. "Cochlear Implantation in Pendred Syndrome." Cochlear Implants International: An Interdisciplinary Journal 12.3 (2011): 157–63. EBSCO Academic Search Complete. Web. 11 Aug. 2014.
Landa, Priya, et al. "Lack of Significant Association between Mutations of KCNJ10 or FOXI1 and SLC26A4 Mutations in Pendred Syndrome/Enlarged Vestibular Aqueducts." BMC Medical Genetics 14.1 (2013): 1–7. EBSCO Academic Search Complete. Web. 11 Aug. 2014.
Ladsous, Miriam, et al. "Analysis of the Thyroid Phenotype in 42 Patients with Pendred Syndrome and Nonsyndromic Enlargement of the Vestibular Aqueduct." Thyroid 24.4 (2014): 639–48. EBSCO Academic Search Complete. Web. 11 Aug. 2014.
Maciaszczyk, K., and A. Lewinski. Phenotypes of SLC26A4 Gene Mutations: “Pendred Syndrome and Hypoacusis with Enlarged Vestibular Aqueduct.” Neuroendocrinology Letters 29.1 (2008): 29–36. Print
"Pendred Syndrome." Genetics Home Reference. National Library of Medicine, 4 Aug. 2014. Web. 11 Aug. 2014.
"SLC26A4." Genetics Home Reference. National Library of Medicine, 4 Aug. 2014. Web. 11 Aug. 2014.