Sickle cell anemia is highly prevalent in Central Africa. The disease causes severe manifestations in children requiring treatment. Hydroxyurea is currently the most effective drug treatment. Therefore, we evaluated the use of HU in children living in rural Central Africa. We conducted a clinical trial with HU from November 2017 to February 2020 in the Hôpital Saint Luc de Kisantu in the DR Congo. Patients aged 6 months to 18 years with a moderate or severe form of SCA (Adegoke score) were treated with an initial HU dose of 15mg/kg per day, which was increased gradually in increments of 5mg/kg per day every six months, to a maximally dose of 30mg/Kg/day. To determine the clinical and biological response to the treatment, we compared the clinical and biological data from the first and second year of treatment with the baseline. From the 136 SCA children followed at KSLH, 69 (37 boys and 32 girls; sex-ratio M/F 1.15) started the clinical trial with HU. Of them, 39 patients reached the end of the clinical trial (56.5%). We observed a mean increase in the HbF rate of 3-fold at 12 months and 3.3-fold at 24 months, with a significant difference from the baseline. Thirty-seven (80.4%) patients presented a good clinical response, and 9 (19.6%) did not respond. In conclusion, our clinical trial showed the effectiveness of HU treatment clinically and biologically. Despite tremendous logistical difficulties, HU treatment in a rural area offers the prospect of improving the quality of children with SCA’ life.

Primary microcephaly (PM) is defined as a significant reduction in occipito-frontal circumference (OFC) of prenatal onset. Clinical and genetic heterogeneity of PM represents a diagnostic challenge. We performed detailed phenotypic and genomic analyses in a large cohort (n=169) of patients referred for PM, and could establish a molecular diagnosis in 38 patients. Pathogenic variants in ASPM and WDR62 were the most frequent causes in non-consanguineous patients in our cohort. In consanguineous patients, microarray and targeted gene panel analyses reached a diagnostic yield of 67%, which contrasts with a much lower rate in outbred patients (9%). Our series includes 15 previously unreported families and 11 novel pathogenic variants, and we identify novel candidate genes including IGF2BP3, DNAH2, and TSR1. We confirm progression of microcephaly over time in affected children. Epilepsy was an important associated feature in our PM cohort, affecting 34% of patients, with various degrees of severity and seizure types. Our findings will help to prioritize genomic investigations, accelerate molecular diagnoses and improve management of PM patients.