Pendred syndrome is a disorder typically associated with hearing loss and a thyroid condition called a goiter. A goiter is an enlargement of the thyroid gland , which is a butterfly-shaped organ at the base of the neck that produces hormones. If a goiter develops in a person with Pendred syndrome , it usually forms between late childhood and early adulthood. In most cases, this enlargement does not cause the thyroid to malfunction.
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NCBI Bookshelf. The clinical diagnosis of Pendred syndrome is established in a proband with SNHL, characteristic temporal bone abnormalities identified on thin-cut CT, and euthyroid goiter. In comparison, the clinical diagnosis of nonsyndromic enlarged vestibular aqueduct NSEVA is established in a proband with SNHL and the temporal bone finding of enlargement of the vestibular aqueducts.
It is important to note that in PDS, the temporal bone abnormality can include both EVA and cochlear hypoplasia, an anomaly in which the cochlea has only 1. This distinction is relevant because thyroid enlargement is variably present, depending on methods used to assess thyroid size and nutritional iodine intake.
Treatment of manifestations: Hearing habituation, hearing aids, and educational programs designed for the hearing impaired; consideration of cochlear implantation in individuals with severe-to-profound deafness; standard treatment of abnormal thyroid function. Surveillance: Repeat audiometry every three to six months initially if hearing loss is progressive, then semiannually or annually. Baseline ultrasound examination of the thyroid with periodic ultrasound surveillance to monitor volumetric changes.
When the family-specific pathogenic variants are known, carrier testing for at-risk family members, prenatal testing for pregnancies at increased risk, and preimplantation genetic diagnosis are possible. Sensorineural hearing impairment is usually congenital or prelingual , non-progressive, and severe to profound as measured by auditory brain stem response ABR testing or pure tone audiometry.
The identification and interpretation of temporal bone defects require both the appropriate test i. Computed tomography in a proband with PDS shows absence of the upper turn of the cochlea and deficiency of the modiolus white arrow. EVA is also present black arrow. Inset shows a normal right cochlea and no enlargement of the vestibular aqueduct, more Euthyroid goiter, the typical thyroid defect of Pendred syndrome resulting from an organification defect of iodide, can be detected by volumetric studies to assess thyroid size; however, the ability to document thyroid enlargement depends on the method used to assess thyroid size.
In addition, nutritional iodine intake may prevent thyroid enlargement. If the thyroid is enlarged, thyroid hormone levels can be checked. Note: In the past, an iodine perchlorate discharge test was used to diagnose an organification defect of iodide.
Click here pdf for details of the perchlorate discharge test. The outcome of testing varies by ethnicity and phenotype. Approach to molecular genetic testing. For all persons with hearing loss, the use of a multigene panel for hearing loss and deafness maximizes the diagnostic rate while minimizing the diagnostic expense.
Note: 1 The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
Note: Comprehensive genomic testing i. View in own window. See Table A. Genes and Databases for chromosome locus and protein. See Molecular Genetics for information on allelic variants detected in this gene. Sequence analysis detects variants that are benign, likely benign, of uncertain significance , likely pathogenic, or pathogenic. For issues to consider in interpretation of sequence analysis results, click here.
Methods used may include quantitative PCR , long-range PCR, multiplex ligation-dependent probe amplification MLPA , and a gene -targeted microarray designed to detect single- exon deletions or duplications. Variability in hearing loss and thyroid disease is considerable, even within the same family [ Tsukamoto et al , Napiontek et al ]. Hearing impairment. The degree of hearing impairment and its presentation vary.
Classically, the hearing loss is bilateral, severe to profound, and congenital or prelingual. However, hearing loss may be later in onset and progressive. The progression can be rapid in early childhood [ Stinckens et al ] and may be associated with head injury, infection, or delayed secondary hydrops [ Luxon et al ]. Vertigo can precede or accompany fluctuations in hearing [ Sugiura et al a , Sugiura et al b ]. The often-observed low-frequency air-bone gap in combination with normal tympanometry may represent a "third window" effect caused by the dilated vestibular aqueduct [ Merchant et al ].
Vestibular dysfunction. Vestibular dysfunction should be suspected in infants with normal motor development who episodically experience difficulty walking. Temporal bone abnormalities. The temporal bones are abnormal radiologically in all persons with PDS [ Goldfeld et al ]; however, universal agreement as to the type of abnormality is lacking see Suggestive Findings.
Affected sibs may be discordant for temporal bone anomalies [ Goldfeld et al ]. NSEVA is characterized by sensorineural hearing impairment in the absence of other obvious abnormalities i. Thyroid defects are not seen. Many persons with NSEVA are born with normal hearing and progressively become hearing impaired during childhood. Although several reports have described a correlation between the size of the EVA and the degree of hearing loss, a strict correlation has not been established [ Berrettini et al ].
Persons with EVA may deny vestibular disturbances, although vestibular deficits can be demonstrated by caloric testing. When EVA is unilateral, there is no strict correlation between the side of the vestibular deficit and the side of the vestibular enlargement [ Berrettini et al ]. EVA is the most common imaging finding in persons with sensorineural hearing loss dating from infancy or childhood.
EVA can be bilateral or unilateral. The thyroid phenotype is dependent on the degree of residual iodide transport function in pendrin, the protein encoded by SLC26A4 [ Pryor et al , Pera et al ].
For this reason, loss-of-function variants in SLC26A4 will be associated with impaired iodide organification and reduced iodide efflux into the thyroid follicle. In the absence of pendrin, expression of the chloride channel-5 ClC-5 will also be increased and will transiently compensate for apical iodide efflux.
In more affected follicles, dual oxidase Duox and thyroid peroxidase TPO are relocated in the cytosol, leading to abnormal intracellular thyroid hormone synthesis, which results in cell destruction [ Senou et al ]. Pathogenic variants can occur anywhere in the amino-acid protein. If a novel missense pathogenic variant is identified, it can be very difficult to predict the phenotype i. PDS is also referred to as autosomal recessive sensorineural hearing impairment, enlarged vestibular aqueduct, and goiter.
Biallelic pathogenic variants in FOXI1 have been identified in individuals with hereditary distal renal tubular acidosis. Congenital inherited hearing impairment. Other causes of these types of temporal bone malformations include congenital cytomegalovirus and branchiootorenal syndrome , in which there is no associated thyroid abnormality.
Congenital hypothyroidism with sensorineural hearing loss. Sporadic and endemic congenital hypothyroidism associated with sensorineural hearing impairment is clinically similar to PDS but genetically distinct. Resistance to thyroid hormone. Although the syndrome of resistance to thyroid hormone RTH is typically inherited in an autosomal dominant manner, one exceptional consanguineous kindred in which RTH was inherited in an autosomal recessive manner has been described.
Autoimmune thyroid diseases. Autoimmune thyroid diseases, including Graves' disease, Hashimoto thyroiditis, and primary idiopathic myxedema, are caused by multiple genetic and environmental factors. Based on anecdotal reports that increased intracranial pressure in individuals with enlarged vestibular aqueduct EVA can occasionally trigger a decline in hearing, some physicians recommend avoiding activities like weightlifting and contact sports. The value of this approach is debatable and should be considered on an individual basis.
At-risk relatives should be evaluated for hearing loss, vestibular dysfunction, and thyroid abnormality in the same manner as an affected individual at initial diagnosis see Evaluations Following Initial Diagnosis. If the pathogenic variants in the family are known, molecular genetic testing of sibs is indicated shortly after birth so that appropriate and early support and management can be provided to the child and family.
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. Search ClinicalTrials. Note: There may not be clinical trials for this disorder. Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions.
The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional.
Offspring of a proband. Other family members. Parents of a proband. Both parents should undergo confirmatory genetic testing. Sibs of a proband. Each sib of the proband 's parents will have zero, one, or two pathogenic variants depending on the genetic status of the proband's parent.
Carrier testing for reproductive partners of individuals whose pathogenic variant has been identified may be possible. See Management, Evaluation of Relatives at Risk for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment. DNA banking is the storage of DNA typically extracted from white blood cells for possible future use. Because it is likely that testing methodology and our understanding of genes, allelic variants, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.
Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing, particularly if the testing is being considered for the purpose of pregnancy termination rather than early diagnosis. While most centers would consider decisions regarding prenatal testing to be the choice of the parents, discussion of these issues is appropriate. GeneReviews is not responsible for the information provided by other organizations.
For information on selection criteria, click here. Rare reports of apparent digenic inheritance, in which an affected individual is a double heterozygote heterozygous in each of two of the involved genes , include:. Gene structure. Its two transcript variants encode different isoforms isoform "a" has and isoform "b" has amino acids. For a detailed summary of gene and protein information, see Table A , Gene. Pathogenic variants.
Pendred syndrome is a genetic disorder leading to congenital bilateral both sides sensorineural hearing loss and goitre with euthyroid or mild hypothyroidism decreased thyroid gland function. There is no specific treatment, other than supportive measures for the hearing loss and thyroid hormone supplementation in case of hypothyroidism. It is named after Dr Vaughan Pendred — , the British doctor who first described the condition in an Irish family living in Durham in The hearing loss of Pendred syndrome is often, although not always, present from birth, and language acquisition may be a significant problem if deafness is severe in childhood. The hearing loss typically worsens over the years, and progression can be step-wise and related to minor head trauma. In some cases, language development worsens after head injury , demonstrating that the inner ear is sensitive to trauma in Pendred syndrome; this is as a consequence of the widened vestibular aqueducts usual in this syndrome. Pendred syndrome is inherited in an autosomal recessive manner, meaning that one would need to inherit an abnormal gene from each parent to develop the condition.
ISSN Objective : To present a clinical case of Pendred syndrome, a rare pathology in children that includes congenital deafness and goiter. Clinical case : Preschool female 5 years and 4 months of age, whose mother refers disease of 3 months of evolution characterized by progressive increase in volume of the anterior neck, without redness, heat, or pain; concomitantly drowsiness, constipation and hypoactivity. Physical Examination: Weight Neurological: poor communication with the examiner, she did not obey verbal commands, just by using sign language so that hypoacusia was diagnosed. The otorrino and neurology services pose sensorineural deafness.
Pendred syndrome is an autosomal recessively inherited disorder characterized by a euthyroid goiter associated with sensorineural hearing loss. There is an autosomal recessive pattern inheritance, although this appears complex with most patients being compound heterozygotes. Inner ear malformations are an invariable finding in Pendred syndrome. The most commonly described features are the following 1 :. Please Note: You can also scroll through stacks with your mouse wheel or the keyboard arrow keys. Updating… Please wait. Unable to process the form.
Alternative titles; symbols. There is evidence that Pendred syndrome may also rarely be caused by digenic inheritance of a heterozygous mutation in the SLC26A4 gene and a heterozygous mutation in the FOXI1 gene Pendred syndrome, the most common syndromal form of deafness, is an autosomal recessive disorder associated with developmental abnormalities of the cochlea, sensorineural hearing loss, and diffuse thyroid enlargement goiter Everett et al. For a general phenotypic description and a discussion of genetic heterogeneity of thyroid dyshormonogenesis, see TDH1 A mild type of organification defect is associated with congenital deafness. Their thyroids are moderately enlarged from childhood. Patients are usually euthyroid, although an exaggerated response to thyrotropin-releasing hormone TRH; suggests a compensated hypothyroidism Gomez-Pan et al.
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