Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes.

BACKGROUND: Duplications and deletions in the human genome can cause disease or predispose persons to disease. Advances in technologies to detect these changes allow for the routine identification of submicroscopic imbalances in large numbers of patients. METHODS: We tested for the presence of microdeletions and microduplications at a specific region of chromosome 1q21.1 in two groups of patients with unexplained mental retardation, autism, or congenital anomalies and in unaffected persons. RESULTS: We identified 25 persons with a recurrent 1.35-Mb deletion within 1q21.1 from screening 5218 patients. The microdeletions had arisen de novo in eight patients, were inherited from a mildly affected parent in three patients, were inherited from an apparently unaffected parent in six patients, and were of unknown inheritance in eight patients. The deletion was absent in a series of 4737 control persons (P=1.1x10(-7)). We found considerable variability in the level of phenotypic expression of the microdeletion; phenotypes included mild-to-moderate mental retardation, microcephaly, cardiac abnormalities, and cataracts. The reciprocal duplication was enriched in nine children with mental retardation or autism spectrum disorder and other variable features (P=0.02). We identified three deletions and three duplications of the 1q21.1 region in an independent sample of 788 patients with mental retardation and congenital anomalies. CONCLUSIONS: We have identified recurrent molecular lesions that elude syndromic classification and whose disease manifestations must be considered in a broader context of development as opposed to being assigned to a specific disease. Clinical diagnosis in patients with these lesions may be most readily achieved on the basis of genotype rather than phenotype.

Validity of instruction leaflets for parents to measure their child's weight and height at home: results obtained from a randomised controlled trial.

OBJECTIVES: To compare the validity of parent-reported height, weight and body mass index (BMI) values of children (aged 4-10 years), when measured at home by means of newly developed instruction leaflets in comparison with simple estimated parental reports. DESIGN: Randomised controlled trial with control and intervention group using simple randomisation. SETTING: Belgian children and their parents recruited via schools (multistage cluster sampling design). PARTICIPANTS: 164 Belgian children (53% male; participation rate 62%). INTERVENTION: Parents completed a questionnaire including questions about the height and weight of their child. Parents in the intervention group received instruction leaflets to measure their child's weight and height. Classes were randomly allocated to the intervention and control groups. Nurses measured height and weight following standardised procedures up to 2 weeks after parental reports. OUTCOME MEASURES: Weight, height and BMI category of the child were derived from the index measurements and the parental reports. RESULTS: Mean parent-reported weight was slightly more underestimated in the intervention group than in the control group relative to the index weights. However, for all three parameters (weight, height and BMI), correlations between parental reports and nurse measurements were higher in the intervention group. Sensitivity for underweight and overweight/obesity was respectively, 75% and 60% in the intervention group, and 67% and 43% in the control group. Weighed κ for classifying children in the correct BMI category was 0.30 in the control group and was 0.51 in the intervention group. CONCLUSIONS: Although mean parent-reported weight was slightly more underestimated in the intervention than in the control group, correlations were higher and there was considerably less misclassification into valid BMI categories for the intervention group. This pattern suggests that most of the parental deviations from the index measurements were probably due to random errors of measurement and that diagnostic measures could improve by encouraging parents to measure their children's weight and height at home by means of instruction leaflets.

Perisylvian polymicrogyria, infantile spasms and arthrogryposis: the severe end of the spectrum of congenital bilateral perisylvian polymicrogyria.

Congenital bilateral perisylvian polymicrogyria (CBPP) is the most frequent type of polymicrogyria in children. A 3-month-old male patient is described here with the combination of CBPP, infantile spasms and arthrogryposis. Only four patients have been reported earlier in the literature with this combination. Three of them had epilepsy. These patients represent the more severe phenotype of CBPP, characterized by early onset of symptoms, epilepsy, mental retardation, pseudobulbar palsy and arthrogryposis.