Family Identity and Roles in the Context of Li-Fraumeni Syndrome: "No One's Like Us Mutants".

Li-Fraumeni syndrome (LFS) is a rare hereditary cancer syndrome in which individuals have a significantly increased risk of developing multiple cancers throughout the life span. An LFS diagnosis may shift the individual's sense of self and tolerance of cancer risk as they engage in cancer screening and cancer prevention activities. This study examined the impact of family identity on health decision making, communication, and role function. Forty-five families completed one or more interviews during an annual, protocol-specific cancer screening study. An interdisciplinary team analyzed 66 interviews using interpretive description and modified grounding theory. Thematically, identity emerged as an evolving construct regarding self and/or family, embedded in historical and ongoing experiences with LFS. Notions of individual and shared family identities guided decision making related to healthcare and influenced interpersonal communication and role function between supportive networks and families. Alignment between individual, family, and generational identities may shape engagement in genetic testing, risk management, and family life. Medical teams that are unequipped to address the psychosocial challenges that LFS populations face may include mental health professionals on interprofessional care teams to navigate risk management and consequential familial conflict.

Genetic diversity in Svaneti and its implications for the human settlement of the Highland Caucasus.

OBJECTIVES: In this study, we characterized genetic diversity in the Svans from northwestern Georgia to better understand the phylogeography of their genetic lineages, determine whether genetic diversity in the highland South Caucasus has been shaped by language or geography, and assess whether Svan genetic diversity was structured by regional residence patterns. MATERIALS AND METHODS: We analyzed mtDNA and Y-chromosome variation in 184 individuals from 13 village districts and townlets located throughout the region. For all individuals, we analyzed mtDNA diversity through control region sequencing, and, for males, we analyzed Y-chromosome diversity through SNP and STR genotyping. The resulting data were compared with those for populations from the Caucasus and Middle East. RESULTS: We observed significant mtDNA heterogeneity in Svans, with haplogroups U1-U7, H, K, and W6 being common there. By contrast, ∼78% of Svan males belonged to haplogroup G2a, with the remainder falling into four other haplogroups (J2a1, I2, N, and R1a). While showing a distinct genetic profile, Svans also clustered with Caucasus populations speaking languages from different families, suggesting a deep common ancestry for all of them. The mtDNA data were not structured by geography or linguistic affiliation, whereas the NRY data were influenced only by geography. DISCUSSION: These patterns of genetic variation confirm a complex set of geographic sources and settlement phases for the Caucasus highlands. Such patterns may also reflect social and cultural practices in the region. The high frequency and antiquity of Y-chromosome haplogroup G2a in this region further points to its emergence there.

Genetics healthcare providers' experiences counseling patients with results from consumer genomic testing.

BACKGROUND: Consumer genomic testing (CGT), including direct-to-consumer and consumer-initiated testing, is increasingly widespread yet has limited regulatory oversight. To assess the current state, we surveyed genetics healthcare providers' experiences with CGT. METHODS: A retrospective survey about experiences counseling on CGT results was completed by 139 respondents recruited from the National Society of Genetic Counselors, Clinical Cancer Genomics Community of Practice, and genetics professional societies. RESULTS: Among respondents, 41% disagreed with the statement that potential benefits of CGT outweigh harms, 21% agreed, and 38% were undecided. A total of 94% encountered ≥1 challenge counseling CGT patients, including adverse psychosocial events (76%), incorrect variant interpretation (68%), and unconfirmed results (69%); unconfirmed results were more common among oncology providers (p = 0.03). Providers reporting higher total challenge scores (p = 0.004) or more psychosocial or interpretation challenges (p ≤ 0.01) were more likely to indicate CGT harms outweigh benefits. Those with higher CGT clinical volume were more likely to indicate benefits outweigh harms (p = 0.003). Additional CGT challenges included patient understanding and communication of results, false negatives, incorrect testing/care, and financial costs; seven respondents (6%) documented positive outcomes. CONCLUSION: Providers counseling CGT patients encounter psychosocial and medical challenges. Collaborations between regulators, CGT laboratories, providers, and consumers may help mitigate risks.

Waiting and "weighted down": the challenge of anticipatory loss for individuals and families with Li-Fraumeni Syndrome.

Li-Fraumeni Syndrome (LFS) is characterized by risk of multiple primary malignancies in diverse sites, pediatric onset, near complete penetrance by age 70 years, limited options for prevention, and substantial uncertainty regarding disease manifestation and prognosis. Forty-five families, including 117 individuals aged 13-81 years, enrolled in the US National Cancer Institute's Li-Fraumeni Syndrome Study completed 66 interviews regarding their LFS experiences. An interdisciplinary team used modified grounded theory to examine family distress regarding expectations of loss and change due to likely cancer diagnoses, and the consequences of this likelihood across physical, social, and emotional domains. Disease-free periods were characterized by fearful anticipation of diagnosis or recurrence, uncertainty regarding post-treatment quality of life, and planning for shifts in family dynamics to enable caregiving. The chronicity of waiting for these changes incited dread and inhibited effective coping with the pragmatic, emotional, and existential challenges of the syndrome. Consequently, families reported high burden on roles and resources and limited guidance to prepare for, or achieve resolution with, grief. Anticipatory loss, the experience of bereavement prior to an expected change, distinguishes hereditary cancer risk from a sporadic diagnosis. Such grief is often incomplete in impact or meaning, subjected to rapid or profound change as conditions worsen, and poorly understood. In this study, losses were compounded by profound uncertainty, a chronic feature of LFS, which compromised mourning. Long-term engagement of mental health providers with bereavement training, in partnership with genetics providers, can provide invaluable educational and psychological support to families as they navigate these implacable challenges.