To define the region of 11p15 involved in Beckwith-Wiedemann syndrome (BWS), we have carried out a molecular genetic analysis of six patients with features of BWS and constitutional cytogenetic abnormalities involving chromosome band 11p15. Molecular analysis confirmed the 11p origin of the duplicated material and defined the smallest region of overlap for such duplications, within which a gene involved in BWS must be located. This region encompasses the beta-globin gene complex (HBB) to 11pter. In both of our informative cases, the 11p duplication was found to be of paternal origin. Two BWS associated balanced translocations of 11p15 were studied to localize the breakpoints on 11p15. Somatic cell hybrids, Southern blotting and fluorescent in situ hybridization (FISH) showed that both breakpoints were between D11S12 and the insulin-like growth factor 2 (IGF2) gene. A non-BWS translocation breakpoint was more proximal, between HBB and calcitonin-A (CALCA). Pedigree analysis showed that both BWS associated 11p15 translocations were transmitted by phenotypically normal mothers. The data are compatible with the hypothesis that the BWS gene is imprinted and that the maternally inherited BWS gene is normally suppressed whereas the paternally inherited allele is active. Thus, duplications of paternal origin would lead to increased dosage of the BWS gene. Similarly increased dosage of the BWS gene could account for the findings in maternally inherited 11p15 translocations by altering normal imprinting, so that the translocated maternal allele remains active. This study defines one or more gene loci for BWS on 11p15.5 in the genomic region from D11S12 to IGF2.

Rapid maxillary expansion resulted in a reduction in hearing loss, yearly rate of ENT infections and parentally assessed symptoms of upper airway obstruction, compared with no treatment. These findings are probably related to expanded oronasal space, due to rapid maxillary expansion.

Background/aims-Amblyopia in people with Down's syndrome has not been well investigated. This study was designed to determine the prevalence and associated conditions of amblyopia in a group of home reared children with Down's syndrome. Methods-All children in the study group underwent an evaluation of visual acuity. In addition, previous ophthalmological records were reviewed, and a subgroup of children was examined. For the purposes of this study, amblyopia was defined quantitatively as a diVerence of two Snellen acuity lines between eyes or if unilateral central steady maintained (CSM) vision and a clear fixation preference was observed. A high refractive error was defined as a spherical equivalent more than 3 dioptres and astigmatism more than 1.75 dioptres. Anisometropia was defined as a diVerence of at least 1.5 dioptres of sphere and/or 1.0 dioptre of cylinder between eyes. 68 children with Down's syndrome between the ages of 5 and 19 years were enrolled in the final study group. Results-Amblyopia was observed in 15 (22%) of 68 patients. An additional 16 (24%) patients had bilateral vision less than 20/50. Strabismus, high refractive errors, and anisometropia were the conditions most commonly associated with decreased vision and amblyopia Conclusion-This study suggests that the prevalence of amblyopia is higher than previously reported. Fully 46% of these children with Down's syndrome had evidence of substantial visual deficits. These patients may be at higher risk for visual impairment and should be carefully examined for ophthalmological problems.