Disease Information for Allan-Herndon Mental Retardation/X-linked

Synonyms of Allan Herndon Syndrome; AHDS;

Allan-Herndon-Dudley Mental Retardation; Allan-Herndon-Dudley Syndrome; X-Linked Mental Retardation with Hypotonia

Discussion : Allan-Herndon syndrome is an extremely rare inherited disorder that may be characterized by severe mental retardation, an impaired ability to form words and speak clearly (dysarthria), diminished muscle tone (hypotonia), and/or movement abnormalities; With the exception of poor muscle tone, most affected infants appear to develop normally during the first months of life; However, by about six months of age, affected infants may seem weak and have an inability to hold up the head; Due to hypotonia, severely reduced motor development, and other abnormalities, affected children may not develop the ability to walk or may walk with difficulty; Associated features often include underdevelopment (hypoplasia) and wasting (atrophy) of muscle tissue; weakness and stiffness of the legs (spastic paraplegia) with exaggerated reflexes (hyperreflexia); relatively slow, involuntary, purposeless, writhing movements (athetoid movements); and/or other movement abnormalities; Affected individuals may also have abnormalities of the skull and facial (craniofacial)

region; Allan-Herndon syndrome is thought to be inherited as an X-linked recessive trait and therefore is typically fully expressed in males only----[NORD 2005]----------

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 exclusively in males, disrupts development from before birth; Although affected males have impaired speech and a limited ability to communicate, they seem to enjoy interaction with other people; 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 contractures, 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; Allan-Herndon-Dudley syndrome appears to be a rare disorder; About 25 families with individuals affected by this condition have been reported worldwide; 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 a butterfly-shaped gland in the lower neck called 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 (metabolism); 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

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