RESUMEN
Obtaining forensically relevant information beyond who deposited a biological stain on how and under which circumstances it was deposited is a question of increasing importance in forensic molecular biology. In the past few years, several studies have been produced on the potential of gene expression analysis to deliver relevant contextualizing information, e.g. on nature and condition of a stain as well as aspects of stain deposition timing. However, previous attempts to predict the time-of-day of sample deposition were all based on and thus limited by previously described diurnal oscillators. Herein, we newly approached this goal by applying current sequencing technologies and statistical methods to identify novel candidate markers for forensic time-of-day predictions from whole transcriptome analyses. To this purpose, we collected whole blood samples from ten individuals at eight different time points throughout the day, performed whole transcriptome sequencing and applied biostatistical algorithms to identify 81 mRNA markers with significantly differential expression as candidates to predict the time of day. In addition, we performed qPCR analysis to assess the characteristics of a subset of 13 candidate predictors in dried and aged blood stains. While we demonstrated the general possibility of using the selected candidate markers to predict time-of-day of sample deposition, we also observed notable variation between different donors and storage conditions, highlighting the relevance of employing accurate quantification methods in combination with robust normalization procedures.This study's results are foundational and may be built upon when developing a targeted assay for time-of-day predictions from forensic blood samples in the future.
Asunto(s)
Manchas de Sangre , Humanos , Anciano , Colorantes , Genética Forense/métodos , Transcriptoma , Perfilación de la Expresión Génica , ARN Mensajero/genéticaRESUMEN
The purpose of this study was to assess the neurodevelopmental outcome in a larger cohort of higher order multiple births (HOM). To accomplish this, we analysed the perinatal records of 90 HOM from 28 pregnancies (69 triplets, 16 quadruplets and 5 quintuplets) born at the University Hospital Kiel during the period from 1980 to 1994. Sixty-eight out of 79 surviving children (87.2%) were re-examined at a median age of 7.8 years (range: 3 to 14.5 years). Re-examination included assessment of the neurological, psychomotor (Denver developmental scale, Columbia mental maturity scale), and behavioural (childhood behaviour checklist) status. Perinatal mortality was 12%. In 62% of subjects, neurological and cognitive status at follow-up were completely normal; 32% revealed minor and 6% major neurodevelopmental deficits. Comparison between VLBW and LBW HOM disclosed significantly more neurological deficits, lower IQs and more behaviour problems in children with VLBW. Especially social problems, attention deficit, anxiety and depression symptoms were more frequent in the VLBW HOM than in the LBW HOM group. VLBW HOM parents felt significantly more stressed and VLBW HOM mothers reported reduced coping skills. These findings suggest that the overall cognitive and neurological outcome of HOM surviving the neonatal period is good, but that minor neurocognitive deficits are frequent. LBW HOM have less neurological and behaviour problems than VLBW HOM.
Asunto(s)
Trastornos de la Conducta Infantil/etiología , Trastornos del Conocimiento/etiología , Discapacidades del Desarrollo/complicaciones , Discapacidades del Desarrollo/psicología , Enfermedades del Sistema Nervioso/etiología , Embarazo Múltiple , Adolescente , Niño , Trastornos de la Conducta Infantil/diagnóstico , Preescolar , Trastornos del Conocimiento/diagnóstico , Estudios de Cohortes , Evaluación de la Discapacidad , Femenino , Humanos , Masculino , Progenie de Nacimiento Múltiple , Enfermedades del Sistema Nervioso/diagnóstico , Examen Neurológico , Pruebas Neuropsicológicas , Embarazo , Estudios RetrospectivosRESUMEN
In children with Williams-Beuren syndrome (WBS), disturbed behaviors (neurotic, antisocial, and hyperactive) [Arnold et al., 1985: Dev Med Child Neurol 27:49-59; Udwin et al., 1987: J Child Psychol Psychiat 28:297-309] have been described. To study the behavior disturbances and social-emotional adjustment in children with WBS, a group of N = 19 patients was compared with a control group, matched for age, gender, and nonverbal reasoning abilities. Parents were asked to assess the children's behavior in terms of a list of 20 items of the Child Behavior Checklist (CBCL) [Achenbach and Edelbrock, 1983: Manual for the Child Behavior Checklist] and the Vineland Social Maturity Scale (VSMS) [Lüer et al., 1972: Kurzform der Vineland Social Maturity Scale]. As compared with the control group, children with WBS differ significantly in their social behavior towards strangers. They exhibit no reserve or distancing behavior and would, for instance, follow a stranger without hesitation. They are described as showing a hypersensitivity to sounds that is more pronounced than in the control group. Finally, they are found to be significantly less well-adjusted socially than the control individuals.
Asunto(s)
Trastornos de la Conducta Infantil/psicología , Emociones , Ajuste Social , Niño , Preescolar , Femenino , Humanos , Discapacidad Intelectual/psicología , MasculinoRESUMEN
Crisco [1990: Clin Res 38:536A] reported stability of IQs in a group of 14 children with Williams-Beuren syndrome (WBS) over a 5-year period and concluded that they display a development rate similar to normal children. The aim of our study was to examine the stability of the development of nonverbal reasoning abilities over a period of 2 years using two methods. We studied 18 children with WBS (9 girls, 9 boys) with a mean age of 6.6 years (range: 4.4-10.6 yr) at year one (T1), and approximately two years later (T2) at the average age of 8.6 years (range: 5.11-12.7 yr). The Columbia Mental Maturity Scale (CMM) and the Draw A Person Test were administered. The results show that the IQs resulting from the Draw A Person Test were stable over the 2-year period (T1: mean IQ = 63.5, T2: mean IQ = 65, t = 0.63), and display a significant correlation between the two methods (r = 0.547, P = 0.01). Furthermore, the correlation between the two tests (CMM and Draw A Person Test) at the second assessment is high and significant (r = 0.56, P = 0.01). The mean IQs at T2 can be classified as mild mental retardation. A notable result is the significant decrease of the IQs according to the CMM (T1: mean IQ = 77, T2: mean IQ = 68, t = 2.69, P = 0.01). These results suggest that the developmental outcome of children with WBS varies in specific areas of cognitive function over a 2-year period.
Asunto(s)
Desarrollo Infantil , Cognición , Síndrome de Williams/psicología , Niño , Preescolar , Femenino , Humanos , Discapacidad Intelectual , Inteligencia , Pruebas de Inteligencia , Discapacidades para el Aprendizaje , Estudios Longitudinales , Masculino , Pruebas Psicológicas , Valores de Referencia , Factores de TiempoRESUMEN
In recent studies children with Williams-Beuren syndrome (WBS) have been characterized as having a distinct neuropsychological profile with verbal abilities being superior to visuo-spatial and motor skills. An unusual command of language, including excessive use of verbal stereotypes, social phrases, and clichés has been noticed. The aim of this study is to establish whether the quality and quantity of verbal behavior, and the articulation and tonal quality of the voices of children with WBS differ from other children with nonspecific developmental disabilities. A group of 25 children with WBS and a control group of 25 children matched for age (4-10 years), sex (12 girls; 13 boys), and non-verbal reasoning abilities (mean IQ = 79) were investigated. The Heidelberg Language Development Test and a picture story were administered. The mothers were asked to answer a questionnaire to assess the articulation and the vocal characteristics of their children. The results show that children with WB syndrome do not differ in most qualitative and quantitative tasks with regard to verbal competence. They produce significantly more correct plural-singular formations than the control children (t = 2.49, P < 0.01) on a primitive level of grammatical competence. In general, their articulation was reported to be more exact and clear (t = -2.73, P < 0.006). More mothers of children with WBS noticed a production of stereotypes, the use of social phrases, and clichés than did mothers of the control children (Chi square = -6.67 P < 0.005). Children with WBS were less likely to lisp as compared to the control children (Chi square = 2.08, P = 0.074).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Cara/anomalías , Trastornos del Crecimiento/psicología , Lingüística , Trastornos de la Articulación/psicología , Niño , Preescolar , Discapacidades del Desarrollo/psicología , Femenino , Humanos , Discapacidad Intelectual/psicología , Desarrollo del Lenguaje , Masculino , Conducta Estereotipada , Síndrome , Conducta Verbal , VozRESUMEN
Five sets of monozygotic (MZ) twins with Williams-Beuren syndrome (WBS) have been reported so far. We report on an additional pair of mz twins concordant for WBS but variable expression for the syndrome. Although both faces look different monozygosity of the twins was proven by DNA fingerprint analysis, HLA, and blood group pattern. Both girls had the typical facial appearance with strabismus. Both had developmental delay, mild supravalvular aortic stenosis (SVAS), hypoplasia of both pulmonary arteries and multiple peripheral pulmonary stenoses, and inguinal hernia. Unilateral renal agenesis was seen in one of the twins. In addition the pedigree pointed to a second disorder with probably autosomal dominant inheritance. Both twins had a cleft palate, but their father had cleft lip and the grandfather as well as the greatgrandfather had cleft lip/palate. Findings of linkage analysis in pedigrees with nonsyndromic oral facial cleft were taken to suggest that a major locus for nonsyndromal oral facial cleft is located on the distal portion of chromosome 6. Linkage studies could serve as a starting point to examine a locus associated with WBS. Our observation and reports on the literature support the hypothesis that WBS is a genetic disorder.
Asunto(s)
Anomalías Múltiples/genética , Estenosis de la Válvula Aórtica/genética , Enfermedades en Gemelos/genética , Gemelos Monocigóticos , Adulto , Preescolar , Dermatoglifia del ADN , Cara/anomalías , Femenino , Humanos , Recién Nacido , Riñón/anomalías , SíndromeRESUMEN
The dermatoglyphic patterns of fingertips and palms of 115 patients with Williams-Beuren syndrome (WBS) were analysed and compared with the data from 199 control individuals from Germany. The following combination of dermatoglyphic patterns appears to be characteristic to WBS: an excess of whorls on all fingertips; high termination values of the main lines D, B, and A; frequent absence of C triradius (C0); high frequencies of ulnar loops on the hypothenar and distal loops on the 2nd, 3rd, and 4th interdigital areas, of distal axial triradii t", and of abnormal palmar creases such as simian crease and Sydney lines. The combination of fingertip and palmar patterns expressed by a "Log.Score-Index," provides a high degree of discrimination between the WBS patients (92%) and the control group (88%). A "phantom picture" for WBS was constructed, which can be used for its diagnosis.
Asunto(s)
Anomalías Múltiples/genética , Dermatoglifia , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/patología , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Cara/anomalías , Femenino , Genes Dominantes , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/genética , Humanos , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Modelos Logísticos , Masculino , SíndromeRESUMEN
Head circumference is considered an important parameter of brain growth and development. Syndrome-specific standards for head circumference in Williams-Beuren syndrome (WBS) are not available to date, although mental retardation is a leading manifestation in the syndrome. Therefore, we investigated head growth in 63 girls (251 measurements) and 88 boys (298 measurements) with WBS between birth and adulthood. Most measurements in both sexes were from the first 4 years of life (n = 162 in girls and n = 189 in boys). Mean (+/- SD) head circumference at birth was 33.39 +/- 1.38 cm and 34.02 +/- 1.44 cm for term girls and boys, respectively. Although head growth in WBS girls and boys was at a slower velocity, the pattern of head circumference was similar to that in the normal population. After the age of 3 months, head circumference started to fall below the normal mean in girls (0.5-2 cm). In boys, mean head circumference was below the normal mean already at 1 month of age (2 cm). The deficit increased to 3 cm from 6 months to 4 years. Adult OFC was 52.85 +/- 1.75 cm (n = 16) compared to 55.70 +/- 1.83 cm (n = 46; P < 0.00001) in WBS women and 55.51 +/- 1.68 cm (n = 30) compared to 57.87 +/- 1.29 cm (n = 31; P < 0.00001) in WBS men. During development, microcephaly is only seen in about one third of WBS patients.
Asunto(s)
Discapacidades del Desarrollo/patología , Trastornos del Crecimiento/patología , Cabeza/patología , Anomalías Múltiples/patología , Adolescente , Encéfalo/crecimiento & desarrollo , Encéfalo/patología , Cefalometría , Niño , Preescolar , Cara/anomalías , Femenino , Humanos , Lactante , Recién Nacido , Discapacidad Intelectual/patología , Masculino , SíndromeRESUMEN
Kidneys and urinary tract were examined systematically by ultrasonography in 130 patients with Williams-Beuren syndrome (59 females, median age 5.5 years; 71 males, median age 6.4 years). In addition, serum creatinine was determined and an analysis was performed. Creatinine clearance was available in 79 patients. Renal angiographic examinations were done in 18 patients, 8 of whom had renal artery narrowing (44%). The incidence of renal anomalies in Williams-Beuren syndrome was 17.7% vs. around 1.5% in the normal population (P < 0.0003). The spectrum of these anomalies ranged from minor anomalies such as bladder diverticula to more severe malformations such as renal aplasia or hypoplasia (in 5 of 130 patients). In nine patients a duplicated kidney was found. A decreased creatinine clearance (two patients), recurrent symptomatic urinary tract infections (four patients), and hypertension were uncommon. Nephrocalcinosis was not found in our patients. Our data demonstrate that the risk of a structural abnormality of the kidneys and the urinary tract is increased 12- to 36-fold in Williams-Beuren syndrome compared to the normal population. Ultrasound screening of the renal system should be part of the first evaluation of WBS patients.
Asunto(s)
Anomalías Congénitas/epidemiología , Riñón/anomalías , Síndrome de Williams/fisiopatología , Adolescente , Adulto , Niño , Preescolar , Anomalías Congénitas/clasificación , Femenino , Humanos , Incidencia , Lactante , Masculino , Persona de Mediana Edad , Arteria Renal/anomalías , Estudios Retrospectivos , Vejiga Urinaria/anomalíasRESUMEN
Body mass index (BMI) is a useful tool for the investigation of obesity or underweight. It follows a typical pattern throughout childhood. During the first few years of life underweight due to feeding problems and gastrointestinal disturbances is considered a common sign in Williams-Beuren syndrome (WBS), whereas obesity is frequently reported in WBS adults. Systematic studies on weight gain and body mass index in WBS do not exist. Therefore, we studied weight gain relative to height expressed as BMI in 82 WBS girls (459 measurements of weight and height) and in 104 WBS boys (562 measurements). At birth BMI was significant lower in WBS than in normal infants in both sexes (P < 0.0001). During the first months of life, mean BMI showed a catch-up from the 3rd to the 10th-50th centiles in WBS infants relative to the normal standards. The further course of BMI was almost parallel to normal development. In addition, a gradual relative increase to the 50th centile of normal was seen in both sexes. In conclusion, weight gain during the first year of life was sufficient. Feeding and gastrointestinal problems seem not to have a severe impact on weight gain in infancy. Until adulthood weight relative to height continuously reached the 50th centile of normal. Thus, obesity is not a common finding in young adults with WBS. The results of this study may serve as a disease-specific reference of BMI development in WBS patients.
Asunto(s)
Anomalías Múltiples , Índice de Masa Corporal , Peso Corporal/fisiología , Adolescente , Adulto , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Recién Nacido , Discapacidad Intelectual/fisiopatología , Masculino , Obesidad/fisiopatología , SíndromeRESUMEN
Williams-Beuren syndrome (WBS) is a contiguous gene syndrome that occurs mainly sporadically, with an estimated frequency of 1:13,700 to 1:25,000 [Grimm and Wesselhoeft, 1980; Martin et al., 1984; Udwin, 1990]. The cases of monozygotic twins concordant for WBS and dizygotic twins discordant for the syndrome have been reported. In addition, a few familial cases have been described since 1993. The clinical diagnosis has been supported by molecular genetic findings in only two patients, however. We herein report on two families in which the WBS was inherited in girls from their mothers. All four patients showed the typical hemizygous deletion at 7q11.23 [46,XX, ish,del(7)(q11.23q11.23) (ELN/LIMK1/D7S-613x1, D7S486/D7S522x2)], but the clinical picture was strikingly variable within and between families.
Asunto(s)
Síndrome de Williams/patología , Adolescente , Adulto , Niño , Preescolar , Deleción Cromosómica , Cromosomas Humanos Par 7/genética , Salud de la Familia , Femenino , Humanos , Lactante , Masculino , Síndrome de Williams/genéticaRESUMEN
Short stature is found in about 50% of children with Williams-Beuren syndrome (WBS). Disease-specific growth curves for the syndrome showed the presence of a pubertal growth spurt in both sexes. Detailed investigations on the hormonal regulation in patients with WBS have not been performed. We studied plasma gonadotropins, sex steroids, adrenal androgens, and insulin-like growth factors (IGF-I and IGF-II) and their binding protein 3 (IGFBP-3) in a large number of WBS patients from infancy to adulthood (n = 23 females, n = 33 males). In most WBS patients, basal LH and FSH levels were within normal limits for age and pubertal stage. Nevertheless, elevated levels for basal LH and FSH were found in 35 and 44% of girls and 3 and 33% of boys, respectively. Estradiol and testosterone levels were elevated in 9.5 and 15.4% of patients, respectively. Dehydroepiandrosterone sulfate levels were elevated for age and pubertal stage in 30% of the girls and in 39% of the boys. IGF-I was within the reference range in both sexes except for 3 patients who showed slightly decreased levels of IGF-I. In 9 of 43 patients, IGF-II levels were decreased below normal. In contrast, 46% of the IGFBP-3 levels were increased above the reference range. From the 18 patients who underwent GnRH testing, five of six adults showed markedly increased basal and stimulated FSH levels and in most cases also elevated LH levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Anomalías Múltiples/fisiopatología , Enanismo/fisiopatología , Hormonas/sangre , Sistema Hipotálamo-Hipofisario/fisiopatología , Adolescente , Adulto , Androsterona/sangre , Niño , Preescolar , Enanismo/sangre , Estradiol/sangre , Femenino , Hormona Folículo Estimulante/sangre , Hormona Liberadora de Gonadotropina/sangre , Hormona del Crecimiento/sangre , Humanos , Lactante , Factor I del Crecimiento Similar a la Insulina/análisis , Discapacidad Intelectual/sangre , Discapacidad Intelectual/fisiopatología , Hormona Luteinizante/sangre , Masculino , Persona de Mediana Edad , Sistema Hipófiso-Suprarrenal/fisiopatología , Síndrome , Testosterona/sangreRESUMEN
OBJECTIVES: The measurement of health-related quality of life (HRQOL) is increasingly important as a means of monitoring population health status over time, of detecting sub-groups within the general population with poor HRQOL, and of assessing the impact of public health interventions within a given population. At present, no standardised instrument exists which can be applied with equal relevance in pediatric populations in different European populations. The collaborative European KIDSCREEN project aims to develop a standardised screening instrument for children's quality of life which will be used in representative national and European health surveys. Participants of the project are centres from Austria, France, Germany, Netherlands, Spain, Switzerland, and United Kingdom. By including the instrument in health services research and health reporting, it also aims at identifying children at risk in terms of their subjective health, thereby allowing the possibility of early intervention. METHODS: Instrument development will be based on constructing a psychometrically sound HRQOL instrument taking into account the existing state of the art. Development will centre on literature searches, expert consultation (Delphi Methods) and focus groups with children and adolescents (8-17 years). According to international guidelines, items will be translated into the languages of the seven participating countries for a pilot test with 2,100 children and their parents in Europe. The final instrument will be used in representative mail and telephone surveys of HRQOL in 1,800 children and their parents per country (total n = 25,200) and normative data will be produced. The potential for implementing the measurement tool in health services and health reporting will also be evaluated in several different research and public health settings. The final analysis will involve national and cross cultural-analysis of the instrument. RESULTS: The international, collaborative nature of the KIDSCREEN project means it is likely to provide many challenges in terms of producing an instrument which is conceptually and linguistically appropriate for use in many different countries, but it will also provide the opportunity to develop, test and implement the first truly cross-national HRQOL instrument developed for use in children and adolescents. This will help to contribute to a better understanding of perceived health in children and adolescents and to identify populations at risk.
Asunto(s)
Indicadores de Salud , Salud Pública , Calidad de Vida , Adolescente , Niño , Intervención Educativa Precoz , Europa (Continente) , Encuestas Epidemiológicas , Humanos , Cooperación Internacional , Tamizaje MasivoRESUMEN
OBJECTIVES: This study assesses the quantity of stress in mothers of children with mental retardation of different etiologies (Williams Syndrome--WS, Down Syndrome--DS, mental retardation of different etiologies--MR) and in mothers of non-disabled children (MA). METHODS: 85 mothers were asked to complete the Parenting Stress Index (PSI) and the Child Behavior Checklist (CBCL). The groups were matched according to the children's age, sex, and verbal comprehension as assessed by the WISC-R. Data on the child's mental age (WISC-R) and the family's socio-economic level were collected. RESULTS: Significant differences were found in the Child Domain, but not in the Parent Domain of the PSI. According to the Child Domain, mothers of children with WS and DS scored significantly higher on the acceptance and demandingness scales, while mothers of children with MR scored higher on the acceptance scale than did mothers of children with MA. Moreover mothers of children with WS displayed the highest scores on the hyperactivity, mood and adaptability scales. Groups did not differ on the level of experienced reinforcement from their child. No significant differences were found in the Parent Domain according to the subscales attachment and social isolation. Mothers of children with DS scored higher than the other groups on the scales: depression, sense of competence and parent health. Mothers of children with MR scored lower on restriction of their role as a parent and relationship to their spouse. The degree of the children's mental retardation as well as conspicuous behavior correlated positively with maternal stress but not the familial socio-economic level or the age of the children. CONCLUSIONS: Generally, mothers of children with mental retardation, regardless of its etiology, find it more difficult to accept their child than do mothers of non-disabled children. Specific behavior problems associated with the behavioral phenotype of a syndrome also influence the level of maternal stress.