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American Journal of Medical Genetics Part A 10/2005; 138(1):70-2. · 2.39 Impact Factor
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Charles E Schwartz,
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
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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.
The American Journal of Human Genetics 08/2005; 77(1):41-53. · 10.60 Impact Factor
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ABSTRACT: FG syndrome is a rare X-linked recessive form of mental retardation, first described by Opitz and Kaveggia in 1974. Based on over 50 reported cases, FG syndrome is associated with agenesis of the corpus callosum, minor facial anomalies (high, broad forehead with frontal cowlick, ocular hypertelorism, down-slanted palpebral fissures, and small cupped auricles), relative macrocephaly, broad thumbs and halluces, and prominent fetal fingertip pads. Affected individuals manifest neonatal hypotonia and severe constipation, which usually resolves during mid-childhood. The hypotonia with joint hyperlaxity evolves into spasticity with joint contractures in later life. Affability, hyperactivity, and excessive talkativeness are noted frequently in patients with FG syndrome. Recently, we described three additional families (six additional patients) with FG syndrome who support the localization of a gene for the FG syndrome in chromosome region Xq12-q21 [Graham JM Jr, Tackels D, Dibbern K, Superneau D, Rodgers C, Corning K, Schwartz CE. 1998. Am J Med Genet 80:145–156.]. Using these same families and one additional sporadic case of FG syndrome, we compared behavioral and personality characteristics of 6 FG boys with other boys with syndromic and nonsyndromic mental retardation: eight with Down syndrome, seven with Prader-Willi syndrome, eight with nonspecific mental retardation, and 13 with Williams syndrome. Using the Vineland Adaptive Behavior Scales, the Reiss Personality Profiles, and the Achenbach Child Behavior Checklist, parents were asked to characterize the behavior and personality of their boys from ages 4 to 10 years. When compared with Williams syndrome, the FG boys had fewer internalizing behaviors and were significantly less anxious and withdrawn but had similar socially oriented, attention-seeking behaviors. On the Reiss Profile, FG boys were also quite similar to Williams syndrome boys. On the Vineland Scales, FG boys demonstrated significant relative strengths in their socialization skills, consistent with their personality, tending to confirm previous descriptions of their personalities. Am. J. Med. Genet. 85:470–475, 1999. © 1999 Wiley-Liss, Inc.
American Journal of Medical Genetics 07/1999; 85(5):470 - 475.
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ABSTRACT: We collected data on growth, psychomotor development, speech and language development, and intellectual function on a cohort of 100 males with the fragile X chromosome and 95 carrier females. The data include information on prenatal growth (33 males), growth during the preadult years (32 males), psychomotor development during the first 2 years (25 males), speech and language development (15 males and 5 females), and intellectual function (93 males, 33 females, and 10 obligate carriers who were cytogenetically normal). Birth measurements appeared normal when plotted on the Usher/McLean curves of newborn infants (mean head circumference - OFC - at 40th centile, length at 60th centile and weight at 55th centile). Following birth, OFC rose above the 50th percentile and continued above average throughout the preadult years, whereas average length was above average for the first 5 years only and weight did not deviate from the normal mean. Psychomotor development lagged behind the norm from birth with affected males requiring nearly twice as long as expected to sit alone, walk unassisted, and say first words clearly. All males and females studied had significant language delay; all except one male had abnormalities of articulation. All on whom a clear voice sample was obtained had low voice pitch, and 80% had a hoarse or harsh quality of voice. Five males had word repetitions or perseverative speech during the preadult years. The mean IQ of the 93 males studied was 33 and regression analysis demonstrated a decrease in intellectual performance with age. Four fifths of the female carriers who expressed the fra(X) had intell-ectual performance in the mentally retarded range and showed similar decrease in performance with age. Obligate female carriers who did not express the fra(X) site had normal IQs (IQ 102 ± 13.3).
American Journal of Medical Genetics 04/1988; 30(1‐2):123 - 142.
