The duplication 17p13.3 phenotype: analysis of 21 families delineates developmental, behavioral and brain abnormalities, and rare variant phenotypes.

Chromosome 17p13.3 is a gene rich region that when deleted is associated with the well-known Miller-Dieker syndrome. A recently described duplication syndrome involving this region has been associated with intellectual impairment, autism and occasional brain MRI abnormalities. We report 34 additional patients from 21 families to further delineate the clinical, neurological, behavioral, and brain imaging findings. We found a highly diverse phenotype with inter- and intrafamilial variability, especially in cognitive development. The most specific phenotype occurred in individuals with large duplications that include both the YWHAE and LIS1 genes. These patients had a relatively distinct facial phenotype and frequent structural brain abnormalities involving the corpus callosum, cerebellar vermis, and cranial base. Autism spectrum disorders were seen in a third of duplication probands, most commonly in those with duplications of YWHAE and flanking genes such as CRK. The typical neurobehavioral phenotype was usually seen in those with the larger duplications. We did not confirm the association of early overgrowth with involvement of YWHAE and CRK, or growth failure with duplications of LIS1. Older patients were often overweight. Three variant phenotypes included cleft lip/palate (CLP), split hand/foot with long bone deficiency (SHFLD), and a connective tissue phenotype resembling Marfan syndrome. The duplications in patients with clefts appear to disrupt ABR, while the SHFLD phenotype was associated with duplication of BHLHA9 as noted in two recent reports. The connective tissue phenotype did not have a convincing critical region. Our experience with this large cohort expands knowledge of this diverse duplication syndrome.

Patients' resistance to risk information in genetic counseling for BRCA1/2.

BACKGROUND: Risk information from health care providers is relevant to and used in nearly all medical decisions. Patients often misunderstand their risks, yet little is known about the risk perception that patients derive from risk communications with health care providers. This study examines patients' risk perceptions following communication with health care providers during genetic counseling about the risks of breast cancer and BRCA1/2 mutations. METHODS: A prospective, longitudinal study was conducted from October 2002 to February 2004 of women who received genetic counseling. The women completed a survey before their counseling and a telephone interview in the week after the counseling. Main outcome measures included change from precounseling in risk perception and accuracy of postcounseling risk perception (relative to actual risk information communicated). RESULTS: A total of 108 women agreed to participate in the study. The women's postcounseling risk perceptions were significantly lower than their precounseling risk perceptions (breast cancer: 17%, P<.001; mutation: 13%, P<.001) but were significantly higher than the actual risk information communicated (breast cancer: 19%, P<.001; mutation: 24%, P<.001). Accuracy of breast cancer risk perception but not mutation risk perception was associated with precounseling worry (P = .04), even after adjusting for trait anxiety (P = .01). CONCLUSIONS: This research demonstrates patients' resistance to risk information. Inappropriately high risk perception derived from a risk communication with a health care provider can lead patients to make different, and potentially worse, medical decisions than they would with an accurate risk perception and to be unnecessarily distressed about their risk.