Genotype-phenotype correlations in Rubinstein-Taybi syndrome.

Rubinstein-Taybi syndrome (RTS) is a rare multiple congenital anomaly/intellectual impairment syndrome. Loss of function in CREBBP or EP300 genes has been found in about 50% of patients with RTS. Genotype-phenotype correlations were investigated in 93 patients meeting diagnostic criteria for RTS during 2 international RTS family conferences. Mutation analysis of CREBBP was performed on all 31 coding exons and exon-intron junctions; a subset of patients had FISH analysis for large deletions. A total of 64 different variations were observed in the DNA sequence, and determined to be definitive mutations in 52 patients (56%). Mutations detected included: 10 missense mutations; 36 truncating or splice-site mutations; and 6 large deletions detectable by FISH. Fourteen patients had synonymous changes of unknown significance. The majority of mutations affected the HAT domain of CREBBP or predicted termination of the protein before the HAT region. Extensive phenotypic data were collected on each patient and analyzed to determine correlations with mutation types, that is, truncating, large deletions, single amino acid substitutions, or no CREBBP mutation. All four groups displayed the characteristic facial and thumb dysmorphology. Growth retardation in height and weight was seen more frequently in patients with no CREBBP mutation; seizure disorder was more frequent in those with CREBBP mutations. Degree of mental retardation was similar in all groups, although there was a trend toward lower IQ and autistic features in patients with large deletions. Similarity in phenotype between the groups implies that the several genes involved in causing RTS likely have effects through the same pathway.

Bed-wetting in US children: epidemiology and related behavior problems.

OBJECTIVE: To better understand the epidemiology and behavioral correlates of bed-wetting in a nationally representative sample of children. METHODS: Bivariate and multivariate logistic regression analyses of cross-sectional data regarding 10 960 children aged 5 through 17 years from the 1981 Child Health Supplement to the National Health Interview Survey. Behavior problems were determined by extreme scores on a 32-item Behavior Problem Index (BPI, > 90th percentile). RESULTS: Bed-wetting was reported in 33% of 5-, 18% of 8-, 7% of 11-, and 0.7% of 17-years-olds. At all ages, infrequent bed-wetting (fewer than six episodes per year) accounted for half of all reported bed-wetting. Lower age, male gender, and extreme scores on the BPI all were independently associated with both infrequent and frequent bed-wetting. Extreme scores on the BPI were more common among children with bed-wetting than those who did not wet the bed, and the risk for this was similar among children with infrequent and frequent bed-wetting (adjusted odds ratios, 1.8 and 1.7, respectively). Parents' perceived need for help with emotional and behavioral problems, however, was increased only among children with frequent bed-wetting. CONCLUSIONS: Bed-wetting in children aged 5 years and older, irrespective of its frequency, is associated with increased rates of behavior problems. Thus, although infrequent bed-wetting may not warrant medical intervention, this condition should prompt health care providers to explore behavioral issues in greater depth.

Supernumerary chromosome marker (1) in a developmentally delayed child.

A 15-month-old boy with mild developmental delay and several minor anomalies was found to be mosaic 46,XY/47,XY ,+mar(1). The marker r(1) was a small de novo ring identified by FISH with a painting type DNA probe.