Pendred syndrome
Encyclopedia
Pendred syndrome or Pendred disease is a genetic disorder
leading to congenital bilateral (both sides) sensorineural hearing loss
and goitre
with occasional 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 Dr Vaughan Pendred (1869–1946), the English
doctor who first described the condition in an Irish
family living in Durham
in 1896. It accounts for 7.5% of all cases of congenital deafness.
, 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 is present in 75% of all cases.
(measuring ability to hear sounds of a particular pitch) is usually abnormal, but the findings are not particularly specific and an audiogram is not sufficient to diagnose Pendred's syndrome. 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 known as Mondini dysplasia
. Genetic testing 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
are performed to identify mild cases of thyroid dysfunction even if they are not yet causing symptoms.
Pendred syndrome inherits in an autosomal recessive 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's syndrome has a 25% chance of also having the condition.
It has been linked to mutation
s in the PDS gene
, which codes for the pendrin
protein (solute carrier family 26, member 4, SLC26A4). The gene is located on the long arm of chromosome 7
(7q31). Mutations in the same gene also cause enlarged vestibular aqueduct syndrome (EVA or EVAS), another congenital cause of deafness; specific mutations are more likely to cause EVAS, while others are more linked with Pendred syndrome.
(part of the inner ear), thyroid
and the kidney
. In the kidney, it participates in the secretion of bicarbonate
. However, Pendred's 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).
, and cochlear implant
s, may improve language skills. If thyroid hormone levels are decreased, thyroxine
may be required. Patients are advised to take precautions against head injury.
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
leading to congenital bilateral (both sides) sensorineural hearing loss
Sensorineural hearing loss
Sensorineural hearing loss is a type of hearing loss in which the root cause lies in the vestibulocochlear nerve , the inner ear, or central processing centers of the brain....
and goitre
Goitre
A goitre or goiter , is a swelling in the thyroid gland, which can lead to a swelling of the neck or larynx...
with occasional hypothyroidism
Hypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...
(decreased thyroid gland
Thyroid
The thyroid gland or simply, the thyroid , in vertebrate anatomy, is one of the largest endocrine glands. The thyroid gland is found in the neck, below the thyroid cartilage...
function). There is no specific treatment, other than supportive measures for the hearing loss and thyroid hormone
Thyroid hormone
The thyroid hormones, thyroxine and triiodothyronine , are tyrosine-based hormones produced by the thyroid gland primarily responsible for regulation of metabolism. An important component in the synthesis of thyroid hormones is iodine. The major form of thyroid hormone in the blood is thyroxine ,...
supplementation in case of hypothyroidism. It is named Dr Vaughan Pendred (1869–1946), the English
England
England is a country that is part of the United Kingdom. It shares land borders with Scotland to the north and Wales to the west; the Irish Sea is to the north west, the Celtic Sea to the south west, with the North Sea to the east and the English Channel to the south separating it from continental...
doctor who first described the condition in an Irish
Ireland
Ireland is an island to the northwest of continental Europe. It is the third-largest island in Europe and the twentieth-largest island on Earth...
family living in Durham
Durham
Durham is a city in north east England. It is within the County Durham local government district, and is the county town of the larger ceremonial county...
in 1896. It accounts for 7.5% of all cases of congenital deafness.
Signs and symptoms
The hearing loss of Pendred's 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 injuryHead injury
Head injury refers to trauma of the head. This may or may not include injury to the brain. However, the terms traumatic brain injury and head injury are often used interchangeably in medical literature....
, 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 is present in 75% of all cases.
Diagnosis
AudiometryAudiometry
Audiometry is the testing of hearing ability, involving thresholds and differing frequencies. Typically, audiometric tests determine a subject's hearing levels with the help of an audiometer, but may also measure ability to discriminate between different sound intensities, recognize pitch, or...
(measuring ability to hear sounds of a particular pitch) is usually abnormal, but the findings are not particularly specific and an audiogram is not sufficient to diagnose Pendred's syndrome. A thyroid goitre may be present in the first decade and is usual towards the end of the second decade. MRI scanning
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
of the inner ear usually shows widened or large vestibular aqueducts with enlarged endolymphatic sacs and may show abnormalities of the cochleae known as Mondini dysplasia
Mondini Dysplasia
Mondini Dysplasia, is an abnormality in the inner ear that can be the cause of hearing loss.A person with Mondini dysplasia has a cochlea that is incomplete. A normal cochlea has two and a half turns, a cochlea with Mondini dysplasia has two, one and a half, one, or no turns...
. Genetic testing 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
Thyroid function tests 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 or hypothyroidism , or to monitor the effectiveness of either thyroid-suppression or hormone replacement therapy...
are performed to identify mild cases of thyroid dysfunction even if they are not yet causing symptoms.
Genetics
It has been linked to mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s in the PDS gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
, which codes for the pendrin
Pendrin
Pendrin also known as sodium-independent chloride/iodide transporter is a protein that in humans is encoded by the SLC26A4 gene .- Function :Pendrin is an ion exchanger found in the cortical collecting duct....
protein (solute carrier family 26, member 4, SLC26A4). The gene is located on the long arm of chromosome 7
Chromosome 7 (human)
Chromosome 7 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 7 spans more than 158 million base pairs and represents between 5 and 5.5 percent of the total DNA in cells.Identifying genes on each chromosome is an active area of genetic...
(7q31). Mutations in the same gene also cause enlarged vestibular aqueduct syndrome (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 cochleaCochlea
The cochlea is the auditory portion of the inner ear. It is a spiral-shaped cavity in the bony labyrinth, making 2.5 turns around its axis, the modiolus....
(part of the inner ear), thyroid
Thyroid
The thyroid gland or simply, the thyroid , in vertebrate anatomy, is one of the largest endocrine glands. The thyroid gland is found in the neck, below the thyroid cartilage...
and the kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
. In the kidney, it participates in the secretion of bicarbonate
Bicarbonate
In inorganic chemistry, bicarbonate is an intermediate form in the deprotonation of carbonic acid...
. However, Pendred's 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).
Treatment
No specific treatment exists for Pendred syndrome. Speech and language supportSpeech and language pathology
Speech-Language Pathology specializes in communication disorders.The main components of speech production include: phonation, the process of sound production; resonance, opening and closing of the vocal folds; intonation, the variation of pitch; and voice, including aeromechanical components of...
, and cochlear implant
Cochlear implant
A cochlear implant is a surgically implanted electronic device that provides a sense of sound to a person who is profoundly deaf or severely hard of hearing...
s, may improve language skills. If thyroid hormone levels are decreased, thyroxine
Thyroxine
Thyroxine, or 3,5,3',5'-tetraiodothyronine , a form of thyroid hormones, is the major hormone secreted by the follicular cells of the thyroid gland.-Synthesis and regulation:...
may be required. Patients are advised to take precautions against head injury.