Allan-Herndon-Dudley syndrome

December 31, 2014

Synonyms

Overview

Allan-Herndon-Dudley syndrome is a rare disorder of brain development that causes moderate to severe intellectual disability 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.

Symptoms

Allan-Herndon-Dudley syndrome causes moderate to severe intellectual disability and problems with movement. They also have impaired speech and a limited ability to communicate. Most children with this condition have weak muscle tone (hypotonia) and underdevelopment of many muscles (muscle hypoplasia). As they get older, they often 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.

Hypotonia
Unable to hold up head at 6 months
Speaking difficulty
Impaired ability to control voluntary movements
Athetoid movements
Motor retardation
Muscle wasting
Joint contractures
Poor reflexes
Long face
Bitemporal narrowing
Large ears
Mental retardation
Impaired ability to control voluntary movements
Lack of control of voluntary leg movements
Weak infant neck muscles
Inability to walk and talk
Underdeveloped muscles (muscle hypoplasia)
Cognitive impairment
Hyperreflexia
Incoordination
Narrow face
Narrow forehead
Neurological speech impairment
Skeletal muscle atrophy
Upslanted palpebral fissure
Abnormal muscle stiffness (spasticity)
Muscle weakness
Involuntary movements of the arms and legs also limit mobility

Causes

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 intellectual disability 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.

Diagnosis

A physical examination, medical history, and numerous tests can aid in diagnosis. Associated features often include underdevelopment and wasting of muscle tissue; weakness and stiffness of the legs with exaggerated reflexes, relatively slow, involuntary, purposeless, writhing movements (athetoid movements); and other movement abnormalities.

he Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers.

Treatment

There is no cure for Allan herndon dudley syndrome nor is there any specific treatment. Treatment is highly individualized. Because patients are usually severely cognitively impaired, special education and structured care is needed. Physical therapy appears to help with some movement problems.

Theoretical considerations suggested TRIAC (triiodothyroacetate or tiratricol, a natural non-classical thyroid hormone) to be beneficial. In 2014, a case was demonstrated in which therapy with TRIAC in early childhood led to significant improvement of cognition and mobility. Currently, the effect of Triac is under investigation in an official clinical trial (NCT02060474, Sponsor: The Erasmus MC, Rotterdam, The Netherlands).