Allan-Herndon-Dudley syndrome
Encyclopedia
Allan–Herndon–Dudley syndrome is a rare disorder of brain
development that causes moderate to severe mental retardation
and problems with movement. This condition, which occurs almost exclusively in male
s, disrupts development from before birth.
It is named eponymously for William Allan
, Florence C. Dudley, and C. Nash Herndon.
Most children with Allan–Herndon–Dudley syndrome have weak muscle tone (hypotonia
) and underdevelopment of many muscles (muscle hypoplasia). As they get older, they usually develop joint deformities called contracture
s, which restrict the movement of certain joints. Abnormal muscle stiffness (spasticity
), muscle weakness, and involuntary movements of the arms and legs also limit mobility. As a result, many people with Allan-Herndon-Dudley syndrome are unable to walk independently and become wheelchair
-bound by adulthood.
Mutations in the SLC16A2
gene
cause Allan–Herndon–Dudley syndrome. The SLC16A2 gene, also known as MCT8, provides instructions for making a protein that plays a critical role in the development of the nervous system
. This protein transports a particular hormone into nerve cells in the developing brain. This hormone, called triiodothyronine
or T3, is produced by the thyroid
. T3 appears to be critical for the normal formation and growth of nerve cells, as well as the development of junctions between nerve cells (synapses) where cell-to-cell communication occurs. T3 and other forms of thyroid hormone also help regulate the development of other organs and control the rate of chemical reactions in the body.
Gene mutations alter the structure and function of the SLC16A2 protein. As a result, this protein is unable to transport T3 into nerve cells effectively. A lack of this critical hormone in certain parts of the brain disrupts normal brain development, resulting in mental retardation and problems with movement. Because T3 is not taken up by nerve cells, excess amounts of this hormone continue to circulate in the bloodstream. Increased T3 levels in the blood may be toxic to some organs and contribute to the signs and symptoms of Allan-Herndon-Dudley syndrome.
This condition is inherited in an X-linked recessive
pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much more frequently than females. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.
In X-linked recessive inheritance, a female with one altered copy of the gene in each cell is called a carrier. She can pass on the mutated gene, but usually does not experience signs and symptoms of the disorder. Carriers of SLC16A2 mutations have normal intelligence and do not experience problems with movement. Some carriers have been diagnosed with thyroid disease, a condition which is relatively common in the general population. It is unclear whether thyroid disease is related to SLC16A2 mutations in these cases.
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
development that causes moderate to severe mental retardation
Mental retardation
Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
and problems with movement. This condition, which occurs almost exclusively in male
Male
Male refers to the biological sex of an organism, or part of an organism, which produces small mobile gametes, called spermatozoa. Each spermatozoon can fuse with a larger female gamete or ovum, in the process of fertilization...
s, disrupts development from before birth.
It is named eponymously for William Allan
William Allan (geneticist)
William Allan was an American physician and geneticist who made pioneering studies in human genetics and hereditary diseases...
, Florence C. Dudley, and C. Nash Herndon.
Most children with Allan–Herndon–Dudley syndrome have weak muscle tone (hypotonia
Hypotonia
Hypotonia is a state of low muscle tone , often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength...
) and underdevelopment of many muscles (muscle hypoplasia). As they get older, they usually develop joint deformities called contracture
Contracture
A muscle contracture is a permanent shortening of a muscle or joint.. It is usually in response to prolonged hypertonic spasticity in a concentrated muscle area, such as is seen in the tightest muscles of people with conditions like spastic cerebral palsy....
s, which restrict the movement of certain joints. Abnormal muscle stiffness (spasticity
Spasticity
Spasticity is a feature of altered skeletal muscle performance in muscle tone involving hypertonia, which is also referred to as an unusual "tightness" of muscles...
), muscle weakness, and involuntary movements of the arms and legs also limit mobility. As a result, many people with Allan-Herndon-Dudley syndrome are unable to walk independently and become wheelchair
Wheelchair
A wheelchair is a chair with wheels, designed to be a replacement for walking. The device comes in variations where it is propelled by motors or by the seated occupant turning the rear wheels by hand. Often there are handles behind the seat for someone else to do the pushing...
-bound by adulthood.
Mutations in the SLC16A2
SLC16A2
Monocarboxylate transporter 8 is a protein that in humans is encoded by the SLC16A2 gene.- Function :MCT8 transports a variety of iodo-thyronines including the thyroid hormones T3 and T4.- Clinical significance :...
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...
cause Allan–Herndon–Dudley syndrome. The SLC16A2 gene, also known as MCT8, provides instructions for making a protein that plays a critical role in the development of the nervous system
Nervous system
The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...
. This protein transports a particular hormone into nerve cells in the developing brain. This hormone, called triiodothyronine
Triiodothyronine
Triiodothyronine, C15H12I3NO4, also known as T3, is a thyroid hormone. It affects almost every physiological process in the body, including growth and development, metabolism, body temperature, and heart rate....
or T3, is produced by the 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...
. T3 appears to be critical for the normal formation and growth of nerve cells, as well as the development of junctions between nerve cells (synapses) where cell-to-cell communication occurs. T3 and other forms of thyroid hormone also help regulate the development of other organs and control the rate of chemical reactions in the body.
Gene mutations alter the structure and function of the SLC16A2 protein. As a result, this protein is unable to transport T3 into nerve cells effectively. A lack of this critical hormone in certain parts of the brain disrupts normal brain development, resulting in mental retardation and problems with movement. Because T3 is not taken up by nerve cells, excess amounts of this hormone continue to circulate in the bloodstream. Increased T3 levels in the blood may be toxic to some organs and contribute to the signs and symptoms of Allan-Herndon-Dudley syndrome.
This condition is inherited in an X-linked recessive
X-linked recessive
X-linked recessive inheritance is a mode of inheritance in which a mutation in a gene on the X chromosome causes the phenotype to be expressed in males and in females who are homozygous for the gene mutation X-linked recessive inheritance is a mode of inheritance in which a mutation in a gene on...
pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much more frequently than females. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.
External links
- GeneReviews/NCBI/NIH/UW entry on MCT8 (SLC16A2)-Specific Thyroid Hormone Cell Transporter Deficiency
- Allan–Herndon–Dudley syndrome at National Library of Medicine