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Case Reports
. 2005 Jul;77(1):41-53.
doi: 10.1086/431313. Epub 2005 May 11.

Allan-Herndon-Dudley syndrome and the monocarboxylate transporter 8 (MCT8) gene

Charles E Schwartz  1 , Melanie M May, Nancy J Carpenter, R Curtis Rogers, Judith Martin, Martin G Bialer, Jewell Ward, Javier Sanabria, Silvana Marsa, James A Lewis, Roberto Echeverri, Herbert A Lubs, Kytja Voeller, Richard J Simensen, Roger E Stevenson
Affiliations
Case Reports

Allan-Herndon-Dudley syndrome and the monocarboxylate transporter 8 (MCT8) gene

Charles E Schwartz et al. Am J Hum Genet. 2005 Jul.

Abstract

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.

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Figures

Figure 1
Figure 1
Partial pedigrees of six kindreds with Allan-Herndon-Dudley syndrome. Blackened squares indicate affected males, and hatched squares indicate males with unrelated neurodevelopmental disorders.
Figure 1
Figure 1
Partial pedigrees of six kindreds with Allan-Herndon-Dudley syndrome. Blackened squares indicate affected males, and hatched squares indicate males with unrelated neurodevelopmental disorders.
Figure 2
Figure 2
Serum levels of free T3 (top panel), free T4 (middle panel), and TSH (bottom panel) in affected males aged 0–5 years, 5–30 years, or >30 years from five of the six kindreds with Allan-Herndon-Dudley syndrome
Figure 3
Figure 3
Appearance of four affected males in K8225. A, IV-1 at age 1 year, showing a normal face. B, III-11 at age 14 years, showing an elongated and myopathic face. C, III-3 at age 28 years, showing synophrys and prominence of the lower lip. D, II-8 at age 39 years, showing an elongated face with prominence of malar areas and an open mouth.
Figure 4
Figure 4
Appearance of four affected males in K9248. A, V-3 at age 22 mo, showing a cupped left ear, depressed nasal bridge, widely anteverted nares, and tenting of the upper lip with short philtrum. B, V-6 at age 5 years, showing incomplete folding of superior helices and short philtrum. C, IV-6 at age 38 years, showing elongated face with widow’s peak, flattening of midface, and square jaw. D, IV-5 at age 40 years, showing a long face with short philtrum.
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References

Web Resources

    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/ (for Allan-Herndon-Dudley syndrome)

References

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