Allan-Herndon-Dudley syndrome was among the first of the X-linked mental 
retardation syndromes to be described (in 1944) and among the first to be 
regionally mapped on the X chromosome (in 1990). Six large families with the 
syndrome have been identified, and linkage studies have placed the gene locus in 
Xq13.2. Mutations in the monocarboxylate transporter 8 gene (MCT8) have been 
found in each of the six families. One essential function of the protein encoded 
by this gene appears to be the transport of triiodothyronine into neurons. 
Abnormal transporter function is reflected in elevated free triiodothyronine and 
lowered free thyroxine levels in the blood. Infancy and childhood in the 
Allan-Herndon-Dudley syndrome are marked by hypotonia, weakness, reduced muscle 
mass, and delay of developmental milestones. Facial manifestations are not 
distinctive, but the face tends to be elongated with bifrontal narrowing, and 
the ears are often simply formed or cupped. Some patients have myopathic facies. 
Generalized weakness is manifested by excessive drooling, forward positioning of 
the head and neck, failure to ambulate independently, or ataxia in those who do 
ambulate. Speech is dysarthric or absent altogether. Hypotonia gives way in 
adult life to spasticity. The hands exhibit dystonic and athetoid posturing and 
fisting. Cognitive development is severely impaired. No major malformations 
occur, intrauterine growth is not impaired, and head circumference and genital 
development are usually normal. Behavior tends to be passive, with little 
evidence of aggressive or disruptive behavior. Although clinical signs of 
thyroid dysfunction are usually absent in affected males, the disturbances in 
blood levels of thyroid hormones suggest the possibility of systematic detection 
through screening of high-risk populations.