Cascade Testing for Fragile X Syndrome in a Rural Setting in Cameroon (Sub-Saharan Africa)

Abstract

Fragile X Syndrome (FXS), an X-linked dominant monogenic condition, is the main genetic cause of intellectual disability (ID) and autism spectrum disorder (ASD). FXS is associated with an expansion of CGG repeat sequence in the Fragile X Mental Retardation gene 1 (FMR1) on chromosome X. Following a neuropediatric assessment of two male siblings who presented with signs of FXS that was confirmed with molecular testing, we provided cascade counselling and testing to the extended family. A total of 46 individuals were tested for FXS; among them, 58.70% (n = 27) were females. The mean age was 9.4 (±5) years for children and 45.9 (±15.9) years for adults. Pedigree analysis suggested that the founder of these families was likely a normal transmitting male. Four out of 19 males with clinical ID were confirmed to have a full mutation for FXS, while 14/27 females had a pathologic CGG expansion (>56 CGG repeats) on one of their X chromosomes. Two women with premature menopause were confirmed of being carriers of premutation (91 and 101 CGG repeats). We also identified maternal alleles (91 and 126 CGG repeats) which expanded to a full mutation in their offspring (>200 CGG repeats). This study is a rare report on FXS from Africa and illustrates the case scenario of implementing genetic medicine for a neurogenetic condition in a rural setting.

Negotiating political power and stigma around fragile X Syndrome in a rural village in Cameroon: A tale of a royal family and a community

“…With a population of approximately 2000 inhabitants, this rural area is historically known to be a locality with a high ID incidence. In 2020, 46 subjects from the royal family were clinically evaluated and screened for FXS, and 18 of them had a mutation on FMR1 (OMIM 309550) (Kengne et al, 2020). Intrigued by the coexistence of traditional narratives to explain the inheritance of this severe condition and a modern genetic diagnosis, we sought P0’s permission to conduct a qualitative study with her family and member of the community, to better understand how people in a rural African setting make sense of genetics and inheritance, and how this condition had affected the family and the community.…”

“…In most African cultures, inherited forms of ID like FXS are usually attributed to interesting ancestral stories that follow an inheritance pattern. They may be related to stigma, gendered blame, or a curse (Meilleur et al, 2011;de Vries et al, 2020). The return of an FXS genetic diagnosis to a Cameroonian family in the rural part of the country unveiled several explanatory beliefs concerning the understanding of FXS and other forms of inherited intellectual disability in this community.…”

“…In this light, this exploratory study attempts to provide an insight into the dynamic relationship of stigma between families with FXS and the community in which they live. In this paper, we present findings from a rural community in Cameroon's western region formally described as having a high ID incidence and where an FXS genetic cluster was identified in the royal family (Kengne et al, 2020). We then elaborate on the different forms of stigma identified in this community and evaluate the strategies that community members and family members use to cope with stigma.…”

Should Feedback of Individual Results be Integrated into the Consent Process in African Genomics? Participants’ Views from an HIV-TB Genomics Research Project in Botswana

“…This was also true for most projects in the Human Heredity for Health in Africa (H3Africa) consortium in 2016, which did not seek explicit consent for the return of results (Munung et al 2016). However, this position is becoming more difficult to justify as many genomics studies are now likely to discover genetic information that is clinically relevant (Kengne Kamga et al 2020;Rotimi and Marshall 2010;Wonkam and de Vries 2020). Many authors also now argue in favor of feedback of genetic results to participants.…”

The introduction of clinical genetic testing in Ethiopia: Experiences and lessons learned

“…Multiple medical genetics services have been recommended for incorporation into all LMICs including patient and provider education, genetic counselor training, carrier and newborn screening and clinical and laboratory diagnostic services (World Health Organization, 2011). In sub‐Saharan Africa (SSA) there are multiple examples of the successful initiation of medical genetics services including prenatal genetic services, genetic testing for hearing loss, and Fragile X syndrome in Cameroon and retinoblastoma services in Kenya (Bosch et al, 2014; He et al, 2014; Hill et al, 2015; Kengne Kamga et al, 2020; Wonkam et al, 2011). Our group has begun medical genetics capacity building in Ethiopia including investigation into the appropriateness of prenatal genetic services, the public's perception of genetic counseling services and have utilized a mobile application, the MiGene Family History App, to identify the prevalence of congenital anomalies and genetic disease in Addis Ababa (Brooks et al, 2019; Jacobs et al, 2020; Quinonez et al, 2019).…”