Usefulness of fragile X checklist and CGG distribution in specialized institutions in Kinshasa, DR Congo

Abstract

Screening for fragile X syndrome (FXS) is essential in children with developmental delay or intellectual disability (ID). In addition, using clinical screening checklists remains of high interest in resource-limited settings. We aimed to gain insight into the prevalence of FXS and the distribution of CGG alleles and to evaluate the usefulness of three checklists in specialized institutions in Kinshasa, DR Congo. We recruited 80 males and 25 females from six specialized institutions in Kinshasa and administered a questionnaire comprising items from the following FXS checklists: Hagerman, Maes, and Guruju. FMR1 CGG repeats were assessed for every patient. About 37% of patients were referable for FX testing based on Hagerman's checklist, 35% for Maes', and 43.80% for Guruju's, but none of them was molecularly confirmed to have FXS. Thus, specificities were 62.86, 64.76, and 56.5%, respectively, for Hagerman, Maes, and Guruju, respectively. The mean CGG allele size was 28.55 ± 2.83 (ranges, 17-48). The 29 CGG was the most frequent allele (24.61%). Thus, existing checklists should not be automatically applied to Congolese patients without adjustments. The distribution of CGG repeats and the number of CGG alleles are similar to other African studies.

A Comprehensive Review of Fragile X Syndrome and Fragile X Premutation Associated Conditions in Africa

“…Lubala et al [ 38 ] in Congo found clinical and behavioral phenotyping with checklists reported by Hagerman et al [ 37 ], Maes et al [ 40 ] and Guruju et al [ 39 ] to be helpful. In contrast, Lumaka et al [ 90 ] in Congo, Central Africa, noted that none of the 105 individuals assessed with checklists reported by previous authors had FXS after molecular testing, further highlighting the need for gene testing for suspected cases. The paucity of genetic services in Africa may result in a lack of accurate data on the prevalence of FXS in Africa and hinders efforts to improve diagnosis and treatment of the condition.…”

“…Another challenge is the limited access to genetic testing, resources, inadequate healthcare infrastructure and specialized healthcare services in many African countries [ 20 , 21 , 22 , 90 ].…”

“…Many countries are advocating for newborn screening for FXS and there have been significant strides made in this regard [ 10 , 65 , 92 ]. Attempts have been made by a few researchers for the possibility of using clinical and behavioral phenotypes as a means of diagnosis in resource-poor settings with conflicting findings [ 38 , 90 ]. Lubala et al [ 38 ] in Congo found clinical and behavioral phenotyping with checklists reported by Hagerman et al [ 37 ], Maes et al [ 40 ] and Guruju et al [ 39 ] to be helpful.…”

Fragile X syndrome in Democratic Republic of Congo: dysmorphic, cognitive and behavioral findings in 14 subjects from three families

“…In the first study to evaluate the prevalence of FXS in central Africa in a systematic way in a high-risk population of individuals attending schools for special education or specialized clinics for persons with ID, not a single case of FXS was diagnosed with molecular testing among 105 individuals (Lumaka et al ., 2019). However, intermediate alleles that are known to be instable have been found in 2/130 chromosomes that were analyzed, suggesting that FXS is very likely to be present in the Congolese population.…”

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

“…However, the risk of expansion of the CGG repeats in a premutation allele to a full mutation overlays the transmission pattern of this syndrome [8,15]. Research on FXS in African population is limited probably due to scarce genomic and genetic services on the continent [16][17][18], and few qualified personnel [19]; only a few scholars have identified families living with FXS through clinical research [20][21][22]. It is likely that with the developing medical genetic services in countries such as Cameroon [18], this situation will gradually improve.…”