Abstract Objectives Congenital adrenal hyperplasia (CAH) remains one of the most challenging endocrine disorders to diagnose, manage, and treat, especially in Africa where there is lack of neonatal screening program, and limited access to care. Data on biomolecular anomaly are sparse, therefore type of mutations are unknown, increasing management challenges and genetic counseling. The present study aims to describe clinical, biomolecular aspects of a group of Cameroonian patients. Methods We did an observational retrospective study at the pediatric endocrinology unit of the Mother and Child Centre of the Chantal Biya Foundation in Yaounde from May 2013 to December 2019, including all patients diagnosed with CAH. Results We consecutively included 31 patients aged less than 21 years, diagnosed CAH. Median age at diagnosis was 1.71 years (IQR 0.08–2.57 years). Abnormal genitalia was the main complain in 48.4%(n=15). The most prevalent genetic anomaly found in our study population (n=24) was on CYP11, found in 16 patients (66.6%) followed by CYP21A2 mutation found in 8 patients. Homozygous mutation of p.Q356X was found in half of patients with 11 hydroxylase deficiency. This mutation was mostly found in people from semi-Bantu tribes, declared non consanguineous. Conclusions 11 hydroxylase deficiency is the most prevalent form of CAH found in this group of Cameroonian children.
Ataxia-telangiectasia (A-T) is a recessive disorder caused by biallelic pathogenic variants of ataxia-telangiectasia mutated (ATM). This disease is characterized by progressive ataxia, telangiectasia, immune deficiency, predisposition to malignancies, and radiosensitivity. However, hypomorphic variants may be discovered associated with very atypical phenotypes, raising the importance of evaluating their pathogenic effects. In this study, multiple functional analyses were performed on lymphoblastoid cell lines from 36 patients, comprising 49 ATM variants, 24 being of uncertain significance. Thirteen patients with atypical phenotype and presumably hypomorphic variants were of particular interest to test strength of functional analyses and to highlight discrepancies with typical patients. Western-blot combined with transcript analyses allowed the identification of one missing variant, confirmed suspected splice defects and revealed unsuspected minor transcripts. Subcellular localization analyses confirmed the low level and abnormal cytoplasmic localization of ATM for most A-T cell lines. Interestingly, atypical patients had lower kinase defect and less altered cell-cycle distribution after genotoxic stress than typical patients. In conclusion, this study demonstrated the pathogenic effects of the 49 variants, highlighted the strength of KAP1 phosphorylation test for pathogenicity assessment and allowed the establishment of the Ataxia-TeLangiectasia Atypical Score to predict atypical phenotype. Altogether, we propose strategies for ATM variant detection and classification.
Purpose: Treatment of femoral epiphysiolysis with major displacement remains a controversial subject. Open repositioning of the epiphysis via a lateral approach as proposed by Dunn allows nearly anatomic restitution but with a high rate of complications. We report our experience with open repositions via an anterior approach which has been more reliable in our hands.Material and methods: During the last decade, we operated nine hips for epiphysiolysis with major displacement, using the anterior approach to spare the medial circumflex artery. External reduction was not attempted. Preoperative and residual displacement were evaluated using the Southwick technique and according to the position of the femoral head in relation to the Klein line. Early after surgery, a bone scintigram was obtained for all hips. We followed these patients to bone maturity, with a mean follow-up of four years.Results: The early postoperative scintigrams did not reveal any case of insufficient uptake in the femoral head. Mean corr...
Purpose: Partial epiphysiodesis of the growth plate due to physeal aggression is a common problem in paediatric patients. Surgical management requires precise imaging. We recall other imaging techniques currently employed and describe a novel method for studying the characteristic features of epiphysiodesis bridges of the growth plate: 3D-magnetic resonance imaging (3D-MRI).Material and methods: We analysed retrospectively MRI series of 27 epiphysiodesis bridges in 23 children (ten boys and thirteen girls) aged 11.3 years (range 2.5 – 15). We recorded information concerning the cause of the physeal aggression, the joint involved, the type of bony bridge (Ogden classification), the clinical deformation, and the proposed treatment. The 27 bridges were studied on coronal MRI acquired with echo-gradient and fat suppression sequences. Data were processed with a manual 3D reconstruction program in 15 minutes to precisely define the localisation, the volume, and the morphology of the bony bridge and the active p...
Purpose Fetal growth is a complex process involving maternal, placental and fetal factors. The etiology of fetal growth retardation remains unknown in many cases. The aim of this study is to identify novel human mutations and genes related to Silver–Russell syndrome (SRS), a syndromic form of fetal growth retardation, usually caused by epigenetic downregulation of the potent fetal growth factor IGF2. Methods Whole-exome sequencing was carried out on members of an SRS familial case. The candidate gene from the familial case and two other genes were screened by targeted high-throughput sequencing in a large cohort of suspected SRS patients. Functional experiments were then used to link these genes into a regulatory pathway. Results We report the first mutations of the PLAG1 gene in humans, as well as new mutations in HMGA2 and IGF2 in six sporadic and/or familial cases of SRS. We demonstrate that HMGA2 regulates IGF2 expression through PLAG1 and in a PLAG1-independent manner. Conclusion Genetic defects of the HMGA2 – PLAG1 – IGF2 pathway can lead to fetal and postnatal growth restriction, highlighting the role of this oncogenic pathway in the fine regulation of physiological fetal/postnatal growth. This work defines new genetic causes of SRS, important for genetic counseling.
