RESUMO
A submicroscopic deletion containing SOX2 was identified at the 3q breakpoint in a child with t(3;11)(q26.3;p11.2) associated with bilateral anophthalmia. Subsequent SOX2 mutation analysis identified de novo truncating mutations of SOX2 in 4 of 35 (11%) individuals with anophthalmia. Both eyes were affected in all cases with an identified mutation.
Assuntos
Anoftalmia/genética , Cromossomos Humanos Par 3 , Análise Mutacional de DNA , Proteínas de Ligação a DNA/genética , Proteínas Nucleares/genética , Códon sem Sentido , Bases de Dados como Assunto , Saúde da Família , Feminino , Deleção de Genes , Proteínas HMGB , Heterozigoto , Humanos , Íntrons , Masculino , Microftalmia/genética , Modelos Genéticos , Dados de Sequência Molecular , Mutação , Fenótipo , Fatores de Transcrição SOXB1 , Fatores de TranscriçãoRESUMO
The course of cognitive-behavioral development in children with intellectual disabilities produced by genetic disorders has only recently begun to be examined systematically. Unfortunately, these studies are few in number. Previously, we examined cognitive-behavioral development in children with the fragile X (FMR1) mutation and found longitudinal decreases in both IQ and adaptive behavior (DQ) scores in most males and females with the full mutation. In this study, we examine longitudinal changes in IQ and DQ in children with neurofibromatosis type 1 (NF1) and Williams-Beuren Syndrome (WBS) by examining differences in composite IQ and DQ scores between the first test (T1) and retest (T2), and compare their developmental trajectory to children with the FMR1 mutation. Sixty-five children with the FMR1 mutation, or NF1, or WBS, ages 4-16 years, were retested two years after initial testing with the Stanford-Binet 4th Edition (SBFE) and the Vineland Adaptive Behavior Scale (VABS). In addition to significant longitudinal declines in IQ and DQ noted previously in children with the FMR1 mutation, we found significant decreases in IQ in males compared to females in the remainder of our sample. We also observed statistically significant decreases in DQ scores among children the FMR1 mutation, as noted previously, but not among children with NF1 or WBS. Moreover, significant declines were found only among males with the FMR1 mutation. Unlike declines in IQ scores, decreases in DQ were not significantly different between males and females.
Assuntos
Desenvolvimento Infantil , Cognição , Síndrome do Cromossomo X Frágil/psicologia , Neurofibromatose 1/psicologia , Síndrome de Williams/psicologia , Adolescente , Criança , Pré-Escolar , Feminino , Proteína do X Frágil da Deficiência Intelectual/genética , Síndrome do Cromossomo X Frágil/genética , Humanos , Masculino , Mutação , Fatores SexuaisRESUMO
Few studies exist of developmental trajectories in children with intellectual disability, and none for those with subtelomeric deletions. We compared developmental trajectories of children with Wolf-Hirschhorn syndrome to other genetic disorders. We recruited 106 children diagnosed with fragile X, Williams-Beuren syndrome, or Wolf-Hirschhorn syndrome, assessing their intellectual and adaptive behavior abilities. We retested 61 children 2 years later. We compared Time 1 and Time 2 difference scores related to genetic disorder, age, initial IQ, or adaptive behavior composite. Results show genetic disorder and initial IQ score were significant factors for IQ differences, but only genetic disorder affected adaptive behavior differences. Results suggest different gene-brain-behavior pathways likely exist for these genetic disorders. Different developmental trajectories will influence the type and intensity of intervention implemented by caregivers.
Assuntos
Desenvolvimento Infantil/fisiologia , Deficiência Intelectual/epidemiologia , Deficiência Intelectual/fisiopatologia , Síndrome de Wolf-Hirschhorn/epidemiologia , Síndrome de Wolf-Hirschhorn/fisiopatologia , Adaptação Psicológica/fisiologia , Adolescente , Criança , Comportamento Infantil/fisiologia , Pré-Escolar , Cognição/fisiologia , Feminino , Síndrome do Cromossomo X Frágil/epidemiologia , Síndrome do Cromossomo X Frágil/genética , Síndrome do Cromossomo X Frágil/fisiopatologia , Genótipo , Humanos , Deficiência Intelectual/genética , Modelos Lineares , Estudos Longitudinais , Masculino , Testes Neuropsicológicos , Síndrome de Williams/epidemiologia , Síndrome de Williams/genética , Síndrome de Williams/fisiopatologia , Síndrome de Wolf-Hirschhorn/genética , Adulto JovemRESUMO
Studies of age-related features of cognitive-behavioral deficits produced by genetic mutations permit us to draw inferences about how brain development may be related cognitive ability as the child ages. Except for Down syndrome (DS) and the fragile X mutation (FRAXA), little is known about the longitudinal changes in cognitive-behavioral development in individuals with genetic abnormalities producing learning disabilities (LD) or mental retardation (MR). The purpose of this prospective study was to compare and contrast age related to cognitive abilities, adaptive and maladaptive behaviors in children and adolescents in the same age range, diagnosed with one of three genetic disorders: the FRAXA mutation, Neurofibromatosis type 1 (NF1) or Williams-Beuren syndrome (WBS). We also sought to examine whether cognitive-behavioral abilities associated with these three genetic disorders were related systematically to age. We examined 108 children, ages 4-15 years, with FRAXA, WBS, or NF1. Results show that there is a significant negative correlation between age and IQ, and between age and adaptive behavior (DQ) scores, in children with FRAXA and WBS, but not in children with NF1. All three groups of children have unusually high proportions of maladaptive behavior, ranging from 1/6 children with NF1 to 2/3 children with FRAXA. Cognitive and adaptive behavior profiles of children with FRAXA and WBS were also surprisingly similar. Our findings suggest the need for examining longitudinal developmental cognitive-behavioral changes in children and adolescents with all genetic disorders that produce LD or MR.