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.

Sixty children with severe reading disabilities were randomly assigned to two instructional programs that incorporated principles of effective instruction but differed in depth and extent of instruction in phonemic awareness and phonemic decoding skills. All children received 67.5 hours of one-to-one instruction in two 50-minute sessions per day for 8 weeks. Both instructional programs produced very large improvements in generalized reading skills that were stable over a 2-year follow-up period. When compared to the growth in broad reading ability that the participants made during their previous 16 months in learning disabilities resource rooms, their growth during the intervention produced effect sizes of 4.4 for one of the interventions and 3.9 for the other. Although the children's average scores on reading accuracy and comprehension were in the average range at the end of the follow-up period, measures of reading rate showed continued severe impairment for most of the children. Within 1 year following the intervention, 40% of the children were found to be no longer in need of special education services. The two methods of instruction were not differentially effective for children who entered the study with different levels of phonological ability, and the best overall predictors of long-term growth were resource room teacher ratings of attention/behavior, general verbal ability, and prior levels of component reading skills.

The neurologic basis of attention deficit-hyperactivity disorder (ADHD) is poorly understood. Based on previous studies that have implicated metabolic deficiencies in the caudate-striatal region in ADHD, we employed magnetic resonance imaging to investigate patterns of morphology of the head of the caudate nucleus in normal and ADHD children. In normal children, 72.7% evidenced a left-larger-than-right (L > R) pattern of asymmetry, whereas 63.6% of the ADHD children had the reverse (L < R) pattern of asymmetry of the head of the caudate nucleus. This reversal of normal asymmetry in ADHD children was due to a significantly smaller left caudate nucleus. The reversal in asymmetry of the head of the caudate was most notable in ADHD males. These results suggest that normal (L > R) morphologic asymmetry in the region of the caudate nucleus may be related to asymmetries observed in neurotransmitter systems implicated in ADHD. The behavioral symptoms of ADHD may reflect disinhibition from normal levels of dominant hemispheric control, possibly correlated with deviations in asymmetric caudate-striatal morphology and deficiencies in associated neurotransmitter systems.

\s=b\ Objective.\p=m-\Todevelop quantitative methods for identifying cerebral anomalies on magnetic resonance images of subjects with language disorders and other learning disabilities. Design.\p=m-\Partially blinded comparison of subjects with dyslexia, unaffected relatives, and a control group balanced for age and socioeconomic status. Criterion standard: clinical diagnosis of dyslexia by physician or learning disabilities specialist on the basis of clinical assessment and family history.Settings.\p=m-\Hospitalpediatric neurology clinic and private reading clinic.Patients and Other Participants.\p=m-\Volunteers: individuals with dyslexia (seven male and two female, aged 15 to 65 years) from professional families; unaffected first-and second\x=req-\ degree relatives (four male and six female, aged 6 to 63 years) available in the geographical area; and controls (five male and seven female, aged 14 to 52 years).Interventions.\p=m-\Gradient echo three-dimensional scan in Seimens 1-Tesla Magnetom; 128 1.25-mm consecutive sagittal images.Main Outcome Measures.\p=m-\(1) Average length of the tem-poral (T) and parietal (P) banks of the planum temporale;(2) interhemispheric coefficients of asymmetry for T and P banks: Left-Right interhemispheric coefficients of asymmetry= (L-R)/[(L+R)/2];(3) intrahemispheric coefficients of asym-metry=(T-P)/[(T+P)/2]; and (4) qualitative assessment of gyral variants in the parietotemporal operculum.Results.\p=m-\All groups had left-sided asymmetry for the temporal bank and right-sided asymmetry for the parietal bank.The group with dyslexia had exaggerated asymmetries, owing to a significant shift of right planar tissue from the temporal to parietal bank. They also had a higher incidence of cerebral anomalies bilaterally (subjects with dyslexia, six of nine; relatives, two of 10; and controls, zero of 12).Conclusions.\p=m-\Quantitative assessment of high-resolution magnetic resonance images can reveal functionally relevant variations and anomalies in cerebral structure. Further refinement of these measurement techniques should improve the diagnosis, classification, and treatment of language disorders and other learning disabilities.Early investigators believed that neuroanatomical cor-

The attention deficit hyperactivity disorder (ADHD) is associated with defective attention and response inhibition and motor restlessness. Inattention, defective response inhibition, and impersistence are more commonly seen in adults with right than with left hemisphere dysfunction. In light of this fact and because children with ADHD not only appear to demonstrate these symptoms but also neglect the left side and have decreased activation of their right neostriatum, we propose that these children have a right hemisphere dysfunction. In addition, because both inattention and defective response inhibition can be seen in children with ADHD and in patients and animals who have frontal lobe and striatal dysfunction, we propose that children with ADHD have dysfunction in a right-sided frontal-striatal system. Motor restlessness may reflect frontal lobe dysfunction due to impairment of the mesocortical dopamine system.

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This study tests the hypothesis that children with attention deficit disorder (ADD) resemble adults with inattention and neglect secondary to right hemisphere dysfunction. A letter cancellation task was administered to seven boys with ADD and five controls. As a group, the subjects with ADD made significantly more overall errors of omission and left-sided errors than controls, suggesting that they resemble adults with right hemisphere dysfunction.

"Executive function" is a term describing the processes required for conscious control of thought, emotion, and action that are central to the management of one's day-to-day life. Executive function is subserved by the prefrontal cortex and related subcortical structures. Disorders affecting the prefrontal cortex-subcortical system are numerous and heterogeneous, but contemporary research has begun to elucidate the mechanisms and consequences of dysfunction in various subsystems with increasing specificity. Prefrontal executive dysfunction results in impaired regulation of cognition, attention, behaviors, arousal, and emotion, all of which have serious and pervasive consequences for functioning across the life span. These executive function deficits are typically difficult to treat, ameliorate, or remediate and require sensitive handling by caretakers. Executive dysfunction can arise as a consequence of many different factors (metabolic, genetic, certain types of epilepsy, cerebral dysgenesis, prematurity, traumatic brain injury, hypoxia, and toxic exposure). The present review delineates the features of prefrontal executive function deficits in children and proposes a roadmap for their diagnosis, treatment, and management.