Pendred syndrome is a
genetic disorder
A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosome abnormality. Although polygenic disorders ...
leading to congenital bilateral (both sides)
sensorineural hearing loss
Sensorineural hearing loss (SNHL) is a type of hearing loss in which the root cause lies in the inner ear, sensory organ (cochlea and associated structures), or the vestibulocochlear nerve (Cranial nerves, cranial nerve VIII). SNHL accounts for a ...
and
goitre
A goitre (British English), or goiter (American English), is a swelling in the neck resulting from an enlarged thyroid gland. A goitre can be associated with a thyroid that is not functioning properly.
Worldwide, over 90% of goitre cases are ...
with euthyroid or mild hypothyroidism (decreased
thyroid gland
The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans, it is a butterfly-shaped gland located in the neck below the Adam's apple. It consists of two connected lobes. The lower two thirds of the lobes are connected by ...
function). There is no specific treatment, other than supportive measures for the hearing loss and
thyroid hormone
File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones triiodothyronine, T3 and T4
rect 376 268 820 433 Thyroid-stimulating hormone
rect 411 200 849 266 Thyrotropin-releasing hormone
rect 297 168 502 200 Hypothalamus
r ...
supplementation in case of hypothyroidism. It is named after Vaughan Pendred (1869–1946), the
British
British may refer to:
Peoples, culture, and language
* British people, nationals or natives of the United Kingdom, British Overseas Territories and Crown Dependencies.
* British national identity, the characteristics of British people and culture ...
doctor who first described the condition in an
Irish family living in
Durham Durham most commonly refers to:
*Durham, England, a cathedral city in north east England
**County Durham, a ceremonial county which includes Durham
*Durham, North Carolina, a city in North Carolina, United States
Durham may also refer to:
Places
...
in 1896.
It accounts for 7.5% to 15% of all cases of congenital
deafness
Deafness has varying definitions in cultural and medical contexts. In medical contexts, the meaning of deafness is hearing loss that precludes a person from understanding spoken language, an audiological condition. In this context it is writte ...
.
[
]
Signs and symptoms
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
A head injury is any injury that results in trauma to the skull or brain. The terms ''traumatic brain injury'' and ''head injury'' are often used interchangeably in the medical literature. Because head injuries cover such a broad scope of inju ...
, 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. Vestibular function varies in Pendred syndrome and vertigo can be a feature of minor head trauma. A goitre
A goitre (British English), or goiter (American English), is a swelling in the neck resulting from an enlarged thyroid gland. A goitre can be associated with a thyroid that is not functioning properly.
Worldwide, over 90% of goitre cases are ...
is present in 75% of all cases.[
]
Genetics
Pendred syndrome is inherited in an autosomal recessive
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...
manner, meaning that one would need to inherit an abnormal gene from each parent to develop the condition. This also means that a sibling of a patient with Pendred syndrome has a 25% chance of also having the condition if the parents are unaffected carriers.
It has been linked to mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...
s in the ''PDS'' gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
, which codes for the ''pendrin
Pendrin is an Anion-exchange, anion exchange protein that in humans is encoded by the ''SLC26A4'' gene (solute carrier family 26, member 4).
Pendrin was initially identified as a sodium-independent chloride-iodide exchanger with subsequent studie ...
'' protein (solute carrier family 26, member 4, SLC26A4). The gene is located on the long arm of chromosome 7
Chromosome 7 is one of the 23 pairs of chromosomes in humans, who normally have two copies of this chromosome. Chromosome 7 spans about 160 million base pairs (the building material of DNA) and represents between 5 and 5.5 percent of the total DN ...
(7q31). Mutations in the same gene also cause enlarged vestibular aqueduct syndrome
Large vestibular aqueduct is a structural deformity of the inner ear. Enlargement of this duct is one of the most common inner ear deformities and is commonly associated with hearing loss during childhood. The term was first discovered in 1791 by ...
(EVA or EVAS), another congenital cause of deafness; specific mutations are more likely to cause EVAS, while others are more linked with Pendred syndrome.
Pathophysiology
SLC26A4 can be found in the cochlea
The cochlea is the part of the inner ear involved in hearing. It is a spiral-shaped cavity in the bony labyrinth, in humans making 2.75 turns around its axis, the modiolus (cochlea), modiolus. A core component of the cochlea is the organ of Cort ...
(part of the inner ear), thyroid
The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans, it is a butterfly-shaped gland located in the neck below the Adam's apple. It consists of two connected lobes. The lower two thirds of the lobes are connected by ...
and the kidney
In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...
. In the kidney, it participates in the secretion of bicarbonate
In inorganic chemistry, bicarbonate (IUPAC-recommended nomenclature: hydrogencarbonate) is an intermediate form in the deprotonation of carbonic acid. It is a polyatomic anion with the chemical formula .
Bicarbonate serves a crucial bioche ...
. However, Pendred syndrome is not known to lead to kidney problems. It functions as an iodide/chloride transporter. In the thyroid, this leads to reduced organification of iodine (i.e. its incorporation into thyroid hormone).[
]
Diagnosis
People with Pendred syndrome present with a hearing loss either at birth or during childhood. The hearing loss is commonly progressive. In early stages it is usually a mixed hearing loss (both conductive and sensorineural hearing loss) because of a third window effect due to the inner ear malformation (widened vestibular aqueducts). A thyroid goitre may be present in the first decade and is usual towards the end of the second decade. MRI scanning of the inner ear usually shows widened or large vestibular aqueducts with enlarged endolymphatic sacs and may show abnormalities of the cochleae that are known as Mondini dysplasia.[ ]Genetic testing
Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...
to identify the pendrin gene usually establishes the diagnosis. If the condition is suspected, a "perchlorate discharge test" is sometimes performed. This test is highly sensitive, but may also be abnormal in other thyroid conditions.[ If a goitre is present, ]thyroid function tests
Thyroid function tests (TFTs) is a collective term for blood tests used to check the function of the thyroid.
TFTs may be requested if a patient is thought to suffer from hyperthyroidism (overactive thyroid) or hypothyroidism (underactive thyroid) ...
are performed to identify mild cases of thyroid dysfunction even if they are not yet causing symptoms.
Treatment
No specific treatment exists for Pendred syndrome. If thyroid hormone levels are decreased, thyroid hormone supplements may be required. Patients are advised to take precautions against head injury.[
]
References
External links
GeneReviews/NCBI/NIH/UW entry on Pendred Syndrome/DFNB4
{{DEFAULTSORT:Pendred Syndrome
Autosomal recessive disorders
Membrane transport protein disorders
Deafness
Syndromes
Congenital disorders of endocrine system
Diseases named after discoverers