10-year follow-up of the Super-Seniors Study: compression of morbidity and genetic factors.

BACKGROUND: Super-Seniors are healthy, long-lived individuals who were recruited at age 85 years or older with no history of cancer, cardiovascular disease, diabetes, dementia, or major pulmonary disease. In a 10-year follow-up, we aimed to determine whether surviving Super-Seniors showed compression of morbidity, and to test whether the allele frequencies of longevity-associated variants in APOE and FOXO3 were more extreme in such long-term survivors. METHODS: Super-Seniors who survived and were contactable were re-interviewed 10 years after initial characterization. Health and lifestyle were characterized via questionnaire. Geriatric tests including the Timed Up and Go (TUG), Geriatric Depression Scale (GDS), Instrumental Activities of Daily Living (IADL) and the Mini-Mental State Exam (MMSE) were administered, and data were compared to results from on average 10 years earlier. As well, genotype and allele frequencies for SNPs rs7412 and rs429358 in APOE, and rs2802292 in FOXO3 were compared to the frequencies in the original collection of Super-Seniors and mid-life controls. RESULTS: Of the 480 Super-Seniors recruited from 2004 to 2007, 13 were alive, contactable, and consented to re-interview (mean age = 100.1 ± 3.3). Eight of these 13 participants (62%) still met Super-Senior health criteria. Diseases that occurred in late life were cardiovascular (5 of 13; 38%) and lung disease (1 of 13; 8%). MMSE and IADL scores declined in the decade between interviews, and GDS and TUG scores increased. The surviving group of centenarians had a higher frequency of APOE and FOXO3 longevity-associated variants even when compared to the original long-lived Super-Senior cohort. CONCLUSIONS: Although physical and mental decline occurred in the decade between interviews, the majority of Super-Seniors re-interviewed still met the original health criteria. These observations are consistent with reports of compression of morbidity at extreme ages, particularly in centenarians. The increased frequency of longevity- associated variants in this small group of survivors is consistent with studies that reported genetics as a larger contributor to longevity in older age groups.

Patient decision-making and the role of the prenatal genetic counselor: An exploratory study.

Despite much theory about how genetic counseling facilitates prenatal decision-making, there are limited data regarding patients' perceptions of the process and the role of the genetic counselor (GC). Our aim in this study was to explore patients' perceptions of their prenatal genetic counseling session, with a focus on their relationship with their GC and how factors inside and outside the session influenced their decision-making about amniocentesis. We performed a qualitative study with patients who had seen a GC after maternal serum screening revealed an increased risk for aneuploidy. Semistructured interviews were transcribed verbatim, and analyzed using a constant comparative method. To complement and triangulate with these data, we used a secondary quantitative measure-the 6-item Satisfaction With Decision-making (SWD) scale, and questionnaires completed by participants' GCs. Eleven patients participated and four predominant themes emerged from our data: (1) being unprepared; (2) recognizing responsibility for decision-making; (3) the burden of responsibility; and (4) the impact of support through affirmation. Despite the underlying tension within these themes, patients reported high satisfaction with their decisions (SWD mean score = 28.5/30, range: 26-30). Patients perceived their GCs to be nonbiased yet supportive in the decision-making process. Patients described feeling affirmed, but not swayed in their decision.

Mosaic embryo transfer-first report of a live born with nonmosaic partial aneuploidy and uniparental disomy 15.

Objective: To inform clinicians of the first known case of a live born diagnosed with syndromic partial trisomy 15 and maternal uniparental disomy 15 resulting from a mosaic embryo transfer (MET). We believe that this case will highlight the need for standardized practice guidelines to address the potential risk of MET and the importance of prenatal follow-up after a pregnancy is achieved from a MET. Design: Case report. Setting: In vitro fertilization with preimplantation genetic testing for aneuploidy (PGT-A) and MET was completed at a fertility clinic in Canada. Postnatal testing and diagnosis were performed at the Medical Genetics Department of a hospital in Canada. Patients: A newborn male with a diagnosis of partial trisomy 15 and uniparental disomy (UPD) 15. Interventions: Mosaic embryo transfer after PGT-A was performed. Diagnostic testing performed after birth included a karyotype, fluorescence in situ hybridization analysis, chromosomal microarray, and microsatellite UPD testing. Main Outcome Measures: Confirmed nonmosaic partial aneuploidy of trisomy 15 and UPD15 in a symptomatic newborn conceived from MET. Results: Singleton pregnancy was achieved after a double embryo transfer involving 1 embryo diagnosed by PGT-A with high-level mosaic trisomy 15 and high-level mosaic deletion on chromosome 20 (mos(del(20)(q11.23-qter)). Routine prenatal screening and detailed fetal ultrasound did not identify any concerns. Postnatal genetic investigations, triggered by feeding difficulties in the newborn period, diagnosed the proband with maternal UPD15 and a supernumerary marker chromosome composed of 2 noncontiguous regions of chromosome 15. This karyotype is likely resulting from incomplete trisomy rescue occurring on the paternal chromosome 15. Conclusions: This case highlights the need for better guidelines and management of pregnancies achieved after MET.