RESUMO
Down syndrome (DS), or trisomy 21, is a common disorder associated with several complex clinical phenotypes. Although several hypotheses have been put forward, it is unclear as to whether particular gene loci on chromosome 21 (HSA21) are sufficient to cause DS and its associated features. Here we present a high-resolution genetic map of DS phenotypes based on an analysis of 30 subjects carrying rare segmental trisomies of various regions of HSA21. By using state-of-the-art genomics technologies we mapped segmental trisomies at exon-level resolution and identified discrete regions of 1.8-16.3 Mb likely to be involved in the development of 8 DS phenotypes, 4 of which are congenital malformations, including acute megakaryocytic leukemia, transient myeloproliferative disorder, Hirschsprung disease, duodenal stenosis, imperforate anus, severe mental retardation, DS-Alzheimer Disease, and DS-specific congenital heart disease (DSCHD). Our DS-phenotypic maps located DSCHD to a <2-Mb interval. Furthermore, the map enabled us to present evidence against the necessary involvement of other loci as well as specific hypotheses that have been put forward in relation to the etiology of DS-i.e., the presence of a single DS consensus region and the sufficiency of DSCR1 and DYRK1A, or APP, in causing several severe DS phenotypes. Our study demonstrates the value of combining advanced genomics with cohorts of rare patients for studying DS, a prototype for the role of copy-number variation in complex disease.
Assuntos
Mapeamento Cromossômico , Cromossomos Humanos Par 21/genética , Síndrome de Down/genética , Trissomia/genética , Humanos , Lactente , Metanálise como Assunto , FenótipoRESUMO
Down syndrome (DS) is the most frequent chromosomal disorder. Commonly, individuals with DS have difficulties with speech and show an unusual quality in the voice. Their phenotypic characteristics include general hypotonia and maxillary hypoplasia with relative macroglossia, and these contribute to particular acoustic alterations. Subjective perceptual and acoustic assessments of the voice (Praat-4.1 software) were performed in 66 children with DS, 36 boys and 30 girls, aged 3 to 8 years. These data were compared with those of an age-matched group of children from the general population. Perceptual evaluations showed significant differences in the group of children with DS. The voice of children with DS presented a lower fundamental frequency (F(0)) with elevated dispersion. The conjunction of frequencies for formants (F(1) and F(2)) revealed a decreased distinction between the vowels, reflecting the loss of articulatory processing. The DS vocalic anatomical functional ratio represents the main distinctive parameter between the two groups studied, and it may be useful in conducting assessments.
Assuntos
Síndrome de Down , Qualidade da Voz , Criança , Pré-Escolar , Síndrome de Down/epidemiologia , Feminino , Humanos , Masculino , Fonética , Acústica da Fala , Distúrbios da Fala/epidemiologia , Distúrbios da Fala/terapia , Percepção da Fala , Fonoterapia/métodosRESUMO
Since previous investigations reported improvements in cognition of patients with dementia after acetyl-L-carnitine therapy and since there is an increased risk for persons with Down syndrome to develop Alzheimer disease, this study was designed to investigate the effect of acetyl-L-carnitine administration on neurological, intellectual, and social functions in adults with Down syndrome. In this double-blind study we enrolled 40 individuals with Down syndrome and administered acetyl-L-carnitine to the study group during a six months period. Specified examinations and psychological tests were given to persons in both the study and control groups at the start of the investigation and at 3, 6, and 9 months. A detailed analysis of the data revealed that acetyl-L-carnitine administration did not enhance central nervous system functions and that it did not benefit persons with Down syndrome.
Assuntos
Acetilcarnitina/administração & dosagem , Cognição/efeitos dos fármacos , Síndrome de Down/tratamento farmacológico , Nootrópicos/administração & dosagem , Adulto , Doença de Alzheimer/tratamento farmacológico , Atenção/efeitos dos fármacos , Seguimentos , Humanos , Testes de Inteligência , Masculino , Comportamento Social , Falha de Tratamento , Escalas de WechslerRESUMO
Down syndrome (DS) is the most common aneuploid disorder at birth. The life expectancy of persons with DS has improved over the last forty years and is now at about sixty years. Phenotypic characteristics include general hypotonia, maxillary hypoplasia with a small oral cavity and a somewhat larger appearing tongue, frequent constricted maxillary arch, nasal obstruction and others. This prospective study assesses the effects of rapid maxillary expansion (RME) on nasal patency of children with DS, using acoustic rhinometry (AR). Twenty four children with DS, aged 5 to 12 years, had been randomly allocated to the RME and control groups. AR was performed to these individuals prior to expansion, approximately one month after, post maximal expansion, and after a 5 months period of retention. The data between the two groups were compared. Rapid maxillary expansion produced a significant augmentation of nasal volume in children who had been treated (p < 0.05) compared to the control group; these results were stable through the period of retention.