Dysmorphism and major anomalies are a main predictor of survival in newborns admitted to the neonatal intensive care unit in the Democratic Republic of Congo.

In Central-Africa, neonatal infections, asphyxia and prematurity are main reasons for admission to the neonatal intensive care unit and major determinants of newborn survival. Also, the outcome of newborns with congenital anomalies is expected to be poor, due to a lack of state-of-the art care. We conducted a study of 102 newborns recruited in the Neonatal Intensive Care Unit (NICU) at the University Hospitals of Kinshasa, DR Congo, to assess the impact of congenital anomalies. The presence of a major anomaly was associated with a hazard ratio of death of 13.2 (95%CI: 3.7-46.7, p < .001). In addition, the presence of three or more minor anomalies was associated with a 4.5-fold increased risk of death (95%CI: 1.1-18.6, p = .04). We conclude that like major anomalies, the presence of three or more minor anomalies should also be given particular attention and that the evaluation of dysmorphism should be promoted in NICU.

X-linked adrenal hypoplasia congenita: a novel DAX1 missense mutation and challenges for clinical diagnosis in Africa.

Adrenal hypoplasia congenita (AHC) is a rare disease. The X-linked form of AHC is caused by deletions or mutations in DAX1 gene and has a variable clinical presentation. To date, no data on X-linked AHC in central Africa are available. Here, we report a Congolese pedigree with several cases of unexplained deaths of male infants. A careful analysis of the pedigree of this family lead to the recognition of an X-linked inheritance pattern, with subsequent confirmation in a female heterozygous carrier of a DAX1 missense mutation c.1274G>T, (p.Arg425Ile).The diagnosis of this condition remains challenging in a developing country, since the manifestations of AHC overlap with those of the much more frequently occurring infections; darkening of the skin is difficult to evaluate and there is a lack of access to routine endocrinological testing. The diagnosis was eventually made based on the family pedigree, evoking an X-linked inheritance pattern. This illustrates the necessity for medical and clinical genetics to be part of the curriculum of medical school in developing countries.

Profil épidémiologique et facteurs associés à l'ictère néonatal chez les nouveau-nés malades, hospitalisés aux Cliniques Universitaires de Kinshasa / Epidemiological profile and factors associated with neonatal jaundice in sick newborns attending Kinshasa University Hospital

Contexte et objectifs. L'ictère néonatal est un symptôme fréquent. L'objectif de la présente étude était d'actualiser le profil épidémiologique et d'identifier les facteurs associés à l'ictère néonatal chez les nouveau-nés malades. Méthodes. Une étude transversale descriptive a été menée de juin 2022 à avril 2023 aux Cliniques Universitaires de Kinshasa. L'étude a concerné les nouveau-nés malades ayant présenté un ictère cutanéomuqueux. Les variables sociodémographiques, périnatales, cliniques et paracliniques ont été recherchées. Résultats. Sur 152 nouveau-nés malades, 102 (67,1%) cas d'ictère ont été identifiés. Les nouveau-nés à terme (72,5%), nés par voie basse (67,6%) et dont les mères avaient présenté des infections uro-génitales (98%) et de groupe sanguin O (53%) rhésus positif (97,1%) étaient les plus représentés. L'ictère s'est manifesté dans la première semaine de vie (85,3 %). La bilirubine sérique totale initiale se situait entre 10 et 15 mmol/L (57,8 %). L'origine infectieuse était notée dans 85 % des cas (Klebsiella pneumoniae dans 50 % des cas). La photothérapie conventionnelle a été utilisée chez 74,5 %. L'accouchement par voie basse était le seul facteur associé (p=0,001). Conclusion : L'ictère néonatal est fréquent chez les nouveau-nés malades. L'étiologie infectieuse doit être recherchée systématiquement. Une prise en charge appropriée permet de réduire la survenue de séquelles neurosensorielles.

Context and objective. Neonatal jaundice is a common symptom. The objective of the present study was to update the epidemiological profile and identify the factors associated with neonatal jaundice in sick newborns. Methods. A descriptive cross-sectional study was conducted from June 2022 to April 2023 at the Kinshasa University Hospital. The study included sick newborns who presented with mucocutaneous jaundice. Sociodemographic, perinatal, clinical and paraclinical variables were sought. Results. Out of 152 sick newborns, 102 (67.1 %) cases of jaundice were identified. Fullterm newborns (72.5 %), born vaginally (67.6 %) and whose mothers had presented with urogenital infections (98 %) and blood group O (53 %) rhesus positive (97.1 %) were the most represented. Jaundice appeared in the first week of life (85.3 %). Baseline total serum bilirubin was between 10 and 15 mmol/L (57.8 %). The infectious origin was noted in 85 % of cases (Klebsiella pneumoniae in 50 % of cases). Conventional phototherapy was used in 74.5 %. Vaginal delivery was the only associated factor (p=0.001). Conclusion. Neonatal jaundice is common in sick newborns. The infectious etiology must be systematically sought. Appropriate management helps reduce the occurrence of neurosensory aftereffects.

A novel heterozygous mutation of three consecutive nucleotides causing Apert syndrome in a Congolese family.

Apert syndrome (OMIM 101200) is a rare genetic condition characterized by craniosynostosis and syndactyly of hands and feet with clinical variability. Two single nucleotides mutations in the linker region between the immunoglobulin-like domains II and IIIa of the ectodomainin the Fibroblast Growth Factor Receptor 2 gene (FGFR2, OMIM 176943) are responsible of the vast majority of cases: c.755C > G; p.Ser252Trp (65%) and c.758C > G; p.Pro253Arg (34%. Three exceptional cases carry multiple substitutions of adjacent nucleotides in the linker region. Here we present a Congolese male patient and his mother, both affected with Apert syndrome of variable severity, carrying a previously undescribed heterozygous mutation of three consecutive nucleotides (c.756_758delGCCinsCTT) in the IgII-IgIIIa linker region. This is the fourth live-born patient to carry a multiple nucleotide substitution in the linker region and is the second alternative amino acid substitutions of the Pro253. Remarkably, this novel mutation was detected in the first Central African patient ever to be tested molecularly for the Apert syndrome. To discriminate between a hitherto unreported mutation and an ethnic specific polymorphism, we tested 105 Congolese controls, and no variation was detected.

Skinfold over toenail is pathognomonic for the popliteal pterygium syndrome in a Congolese family with large intrafamilial variability.

KEY CLINICAL MESSAGE: We report on three related Congolese popliteal pterygium syndrome (PPS) patients concordant only for the skinfold over the toenail. Mutation analysis revealed that the three affected individuals carried a heterozygous missense mutation in the Exon 4, NM_006147.2:c.250C>T; p.Arg84Cys. This is the first molecularly confirmed PPS family from central Africa.