Clinical and genetic characterization of patients with Digeorge syndrome: a single-center, first report from Sudan.

backgroundDiGeorge syndrome (DGS; OMIM #188400), also known as 22q11.2 deletion syndrome, is characterized by cardiac defects, abnormal facial features, thymic hypoplasia, cleft palate, and hypocalcemia. The syndrome is ranked as the second most common chromosomal change after Down’s syndrome, accounting for 1 in 2000 newborns. DGS syndrome is typically diagnosed through CGH and/or FISH analysis in developed countries. However, in low-resource healthcare settings, diagnosis often relies primarily on clinical manifestations due to limited access to genetic testing. The present study, the first of its kind, seeks to deepen the understanding of both the clinical and genetic aspects of DGS among Sudanese patients by employing FISH analysis as a confirmatory test.

methodsBetween 2020 and 2023, 19 patients with DGS as a provisional diagnosis were referred to the Elite Center for Genetic Services for genetic testing and counseling. Cytogenetics and chromosomal analysis were performed following standard protocols, complemented by chromosomal FISH analysis using locus-specific TUPLE1 and α-satellite DNA probes.

resultsOf the 19 patients, 9 (47.4%) were male, and 10 (52.6%) were female, with ages ranging from 2 months to 3 years, and a mean of 11 ± 8.6 months. The most common presentations were CHD in 13 (68.4%), dysmorphic features in 12 (63.2%), and recurrent respiratory tract infections in 9 (47.4%). The least common presenting complaint was intellectual disability in only 2 (10.5%) patients. The echocardiogram revealed isolated heart defects in 9 (47.4%) patients, and only 4 (21.1%) had combined cardiac anomalies. Laboratory tests showed hypocalcemia in all four neonatal patients (21.1%) with a previous history of neonatal convulsions. Conventional cytogenetic analyses were suggestive but non-conclusive {46,XY,?del(22) and 46,XX,?del(22)} for DGS. The complementary FISH analysis confirmed the diagnosis by detecting the microdeletion in the DGCR of chromosome 22.

conclusionsOur study highlights the late presentation of DGS for genetic diagnoses. This may be due to limited access to genetic testing, late referrals from treating physicians, or the high cost of the tests. A key area for future research is the environmental factors, such as skin bleaching, that may contribute to DGS in Sudan and other African populations.