In the last few years, several genes involved in X-specific mental retardation (MR) have been identified by using genetic analysis. Although it is likely that additional genes responsible for idiopathic MR are also localized on the autosomes, cloning and characterization of such genes have been elusive so far. Here, we report the isolation of a previously uncharacterized gene, MEGAP, which is disrupted and functionally inactivated by a translocation breakpoint in a patient who shares some characteristic clinical features, such as hypotonia and severe MR, with the 3p ؊ syndrome. By fluorescence in situ hybridization and loss of heterozygosity analysis, we demonstrated that this gene resides on chromosome 3p25 and is deleted in 3p ؊ patients that present MR. MEGAP͞srGAP3 mRNA is predominantly and highly expressed in fetal and adult brain, specifically in the neurons of the hippocampus and cortex, structures known to play a pivotal role in higher cognitive function, learning, and memory. We describe several MEGAP͞srGAP3 transcript isoforms and show that MEGAP͞srGAP3a and -b represent functional GTPase-activating proteins (GAP) by an in vitro GAP assay. MEGAP͞srGAP3 has recently been shown to be part of the Slit-Robo pathway regulating neuronal migration and axonal branching, highlighting the important role of MEGAP͞srGAP3 in mental development. We propose that haploinsufficiency of MEGAP͞srGAP3 leads to the abnormal development of neuronal structures that are important for normal cognitive function.

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Cognitive therapies for children and adolescents have generally favorable, but probably nonspecific effects on behavior. On the other hand, the specific effects, however, were weak overall. Therapeutic benefit has been demonstrated only for certain individual types of therapy for specific indications.

One of the oldest and probably well-known examples of cerebral palsy is the mummy of the Pharaoh Siptah about 1196–1190 B.C., and a letter from Hippocrates (460–390 B.C.). Cerebral palsy (CP) is one of the most common congenital or acquired neurological impairments in paediatric patients, and refers to a group of children with motor disability and related functional defects. The visible core of CP is characterized by abnormal coordination of movements and/or muscle tone which manifest very early in the development. Resulting from pre- or perinatal brain damage CP is not a progressive condition per se. However, without systematic medical and physiotherapeutic support the dystonia leads to muscle contractions and to deterioration of the handicap. Here we review the three general spastic manifestations of CP hemiplegia, diplegia and tetraplegia, describe the diagnostic procedures and delineate a time schedule for an early intervention.

Abstract. Calcium metabolism and plasma concentrations of vitamin D metabolites were investigated in 27 children on long-term anticonvulsant therapy. Serum calcium was in the low normal range, phosphorus was normal, parathyroid hormone concentrations and alkaline phosphatase were elevated. Plasma 25-hydroxyvitamin D (25-OH D) and 24,25-dihydroxyvitamin D (24,25-(OH)2D) were decreased, but 1,25-dihydroxyvitamin D (1,25-(OH)2D) was normal when compared with a synchronous control group. The serum concentrations of all anticonvulsant drugs given were measured. The decreases in 25-OH D and 24,25-(OH)2D did not depend on the blood level of a single drug, or any combination of drugs given, or on the duration of therapy. The 25-OH D levels were negatively correlated with the number of different drugs used, which may reflect the severity of the neurologic disorder, and therefore with non-specific factors such as exposure to sunlight, nutrition, or physical activity.Our data do not support the hypothesis that anticonvulsant drugs act on vitamin D metabolism. Key words: Calcium metabolism -Vitamin D metabolites - Anticonvulsant drugsAnticonvulsant drugs, particularly diphenylhydantoin (DPH) and phenobarbital (PB), are known to affect calcium metabolism and to cause rickets or osteomalacia [1,2]. In vitro, in the rat, Caspary [3] and Koch et al. [4] found that intestinal absorption of calcium was depressed by DPH but not by PB. The amounts of the vitamin D dependent calcium binding were found to be normal [3].Since PB induces hepatic microsomal enzymes, it has been suggested that due to increased 25-hydroxylase activity PB may increase the availability of25-OH D and its conversion to more polar but less active vitamin D metabolites, thus enhancing plasma clearance of vitamin D and leading to reduced serum and tissue levels of active vitamin D metabolites [5][6][7]. Conversely, in patients receiving anticonvulsant therapy plasma levels of 24,25-(OH)2D were decreased [8], and levels of 1,25-(OH)2D were reported to be normal [9]. It was concluded that in the presence of PB the intestine is less responsive to 1,25-(OH)2D, or that other factors than vitamin D metabolites may impair intestinal calcium transport. [10] found that in epileptic patients on anticonvulsant therapy absorption of calcium from the digestive tract was moderately depressed but that small doses of 1,25-(OH)2D as well as 25-OH D enhanced calcium absorption. They concluded that the sensitivity of the intestine to vitamin D was not impaired in these subjects. These results may indicate that in patients on anticonvulsant therapy the serum calcium, phosphorus, alkaline phosphatase, and parathyroid hormone (PTH) abnormalities are not caused by a defect in 1,25-(OH)2D metabolism or action on the intestine. As vitamin D metabolism is particularly influenced by external factors such as seasonal changes and differences in exposure to sunlight, physical activity and nutritional status, control data may be derived only from carefully matched subjects. This was also cons...

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The causes for the low proportion of explained occupational therapy in young children and the lower use in children with immigration background warrant further research.