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

This study reports on 14 individuals with Fragile X syndrome from 3 Congolese Families. The majority (8/14) were males, with an average age of 18.4 (±11.1 [14-38]) years old. Typical dysmorphic characteristics of Fragile-X syndrome including elongated face, large and prominent ears were found in both males and females with the full mutation. Macroorchidism was found in all post-pubertal boys. The cognitive ability in our cohort varies widely ranging from mild (IQ 50-70) to moderate (IQ 35-49) intellectual disability (Average IQ of 60). All our female patients have ID.

Usefulness of automated image analysis for recognition of the fragile X syndrome gestalt in Congolese subjects.

BACKGROUND: Computer-aided software such as the facial image diagnostic aid (FIDA) and Face2Gene has been developed to perform pattern recognition of facial features with promising clinical results. The aim of this pilot study was to test Face2Gene's recognition performance on Bantu Congolese subjects with Fragile X syndrome (FXS) as compared to Congolese subjects with intellectual disability but without FXS (non-FXS). METHOD: Frontal facial photograph from 156 participants (14 patients with FXS and 142 controls) predominantly young-adults to adults, median age 18.9 age range 4-39yo, were uploaded. Automated face analysis was conducted by using the technology used in proprietary software tools called Face2Gene CLINIC and Face2Gene RESEARCH (version 17.6.2). To estimate the statistical power of the Face2Gene technology in distinguishing affected individuals from controls, a cross validation scheme was used. RESULTS: The similarity seen in the upper facial region (of males and females) is greater than the similarity seen in other parts of the face. Binary comparison of subjects with FXS versus non-FXS and subjects with FXS versus subjects with Down syndrome reveal an area under the curve values of 0.955 (p = 0.002) and 0.986 (p = 0.003). CONCLUSION: The Face2Gene algorithm is separating well between FXS and Non-FXS subjects.

Deep venous thrombosis and acute pericarditis associated with severe acute respiratory syndrome coronavirus 2 infection in a Congolese infant with sickle cell disease: a case report.

BACKGROUND: Since the beginning of the pandemic, no severe pediatric coronavirus disease 2019 cases have been described in Congo. CASE: We studied a 3-month-old male child of Congolese origin who was admitted to the pediatric department with 7-day history of fever, unilateral lower leg swelling, and dyspnea. There was no known history of contact with a coronavirus disease 2019 patient, and all the family members were asymptomatic. Nasopharyngeal swabs done at admission did not detect severe acute respiratory syndrome coronavirus 2. However, serology tests for severe acute respiratory syndrome coronavirus 2 antibodies were positive for immunoglobulin M and negative for immunoglobulin G. Hemoglobin electrophoresis showed hemoglobin A1, hemoglobin A2, hemoglobin F, and hemoglobin S of 46.2%, 2.5%, 19.9%, and 38.4%, respectively. Chest X-ray showed retrocardiac pneumonia in the left lung, and Doppler ultrasound of the left lower limb showed a recent total femoropopliteal venous thrombosis. At day 10 of hospitalization, our patient had classical signs of cardiac tamponade with a voluminous pericardial effusion seen on echocardiographic examination and elevated C-reactive protein, compatible with a diagnosis of constrictive pericarditis. To the best of the authors' knowledge, this is the first report of a case of plausible severe acute respiratory syndrome coronavirus 2 infection associated with venous thrombosis and acute pericarditis in Congo. CONCLUSION: We hypothesized that this case of venous thrombosis and acute pericarditis in a Congolese child with heterozygous sickle cell disease was related to severe acute respiratory syndrome coronavirus 2 infection.

Objective evaluation of facial features in Congolese newborns by facial measurements. The need for population-specific measurements.

The evaluation of dysmorphism is often subjective because many continuous traits are not easily measured or lack normal values. Because many common morphologic profiles vary between populations, population-specific reference ranges of relevant traits are needed. We aim to evaluate the objective assessment of facial dysmorphism in 553 Congolese newborns based on facial measurements. Measurements taken with a ruler were on average larger compared to those with a caliper, but the bias did not depend on the size of the measurement. We therefore introduced a correction factor that allows to use both techniques for facial measurements interchangeably in future studies. The outer canthal distance, palpebral fissure length, and mouth width were significantly larger in Congolese newborns (respectively mean 6.59 [SD 0.48]; mean 2.20 [SD 0.24]; mean 2.78 [SD 0.26]) when compared to references based on European newborns (respectively mean 3.59 [SD 1.76]; mean 4.20 [SD 2.26]; mean 0.47 [SD 1.21]), while the rest of measurements were significantly smaller. The interpupillary distance (IPD) calculated from inner canthal distance and outer canthal distance was not significantly different. We observed a poor agreement between clinical evaluation and measured features (kappa of 0.432). Clinicians were more likely to recognize a face as having wide-spaced eyes when it had been recognized as such during the clinical examination, more than if the child had a high interpupillary distance. This suggests that the measured IPD is not precisely reflecting what is clinically evaluated as wide-spaced eyes.

Holoprosencephaly: A case series from an area with high mining-related pollution.

BACKGROUND: The extraction and processing of copper and cobalt in the African Copperbelt in the Democratic Republic of Congo have led to substantial environmental pollution, causing concerns about possible adverse effects on human health, including birth defects. CASES: We report three neonates with clinically diagnosed holoprosencephaly who were part of a case-control study performed in Lubumbashi between February 2013 and February 2015. One mother had a high concentration of uranium in urine, and high manganese concentrations were found in blood of another mother and in cord blood of one infant. Two of the three fathers had a mining-related job. DISCUSSION: We hypothesize that these cases of holoprosencephaly were connected to mining-related pollution, possibly via epigenetic alterations induced by paternal occupational exposure to toxic metals.

Predictive Model for the Risk of Severe Acute Malnutrition in Children.

BACKGROUND: The nutritional status is the best indicator of the well-being of the child. Inadequate feeding practices are the main factors that affect physical growth and mental development. The aim of this study was to develop a predictive score of severe acute malnutrition (SAM) in children under 5 years of age. METHODS: It was a case-control study. The case group (n = 263) consisted of children aged 6 to 59 months admitted to hospital for SAM that was defined by a z-score weight/height < -3 SD or presence of edema of malnutrition. We performed a univariate and multivariate analysis. Discrimination score was assessed using the ROC curve and the calibration of the score by Hosmer-Lemeshow test. RESULTS: Low birth weight, history of recurrent or chronic diarrhea, daily meal's number less than 3, age of breastfeeding's cessation less than 6 months, age of introduction of complementary diets less than 6 months, maternal age below 25 years, parity less than 5, family history of malnutrition, and number of children under 5 over 2 were predictive factors of SAM. Presence of these nine criteria affects a certain number of points; a score <6 points defines children at low risk of SAM, a score between 6 and 8 points defines a moderate risk of SAM, and a score >8 points presents a high risk of SAM. The area under ROC curve of this score was 0.9685, its sensitivity was 93.5%, and its specificity was 93.1%. CONCLUSION: We propose a simple and efficient prediction model for the risk of occurrence of SAM in children under 5 years of age in developing countries. This predictive model of SAM would be a useful and simple clinical tool to identify people at risk, limit high rates of malnutrition, and reduce disease and child mortality registered in developing countries.

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

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.

Fragile X checklists: A meta-analysis and development of a simplified universal clinical checklist.

BACKGROUND: Clinical checklists available have been developed to assess the risk of a positive Fragile X syndrome but they include relatively small sample sizes. Therefore, we carried out a meta-analysis that included statistical pooling of study results to obtain accurate figures on the prevalence of clinical predictors of Fragile X syndrome among patients with intellectual disability, thereby helping health professionals to improve their referrals for Fragile X testing. METHODS: All published studies consisting of cytogenetic and/or molecular screening for fragile X syndrome among patients with intellectual disability, were eligible for the meta-analysis. All patients enrolled in clinical checklists trials of Fragile X syndrome were eligible for this review, with no exclusion based on ethnicity or age. Odds ratio values, with 95% confidence intervals as well as Cronbach coefficient alpha, was reported to assess the frequency of clinical characteristics in subjects with intellectual disability with and without the fragile X mutation to determine the most discriminating. RESULTS: The following features were strongly associated with Fragile X syndrome: skin soft and velvety on the palms with redundancy of skin on the dorsum of hand [OR: 16.85 (95% CI 10.4-27.3; α:0.97)], large testes [OR: 7.14 (95% CI 5.53-9.22; α: 0.80)], large and prominent ears [OR: 18.62 (95% CI 14.38-24.1; α: 0.98)], pale blue eyes [OR: 8.97 (95% CI 4.75-16.97; α: 0.83)], family history of intellectual disability [OR: 3.43 (95% CI 2.76-4.27; α: 0.81)] as well as autistic-like behavior [OR: 3.08 (95% CI 2.48-3.83; α: 0.77)], Flat feet [OR: 11.53 (95% CI 6.79-19.56; α:0.91)], plantar crease [OR: 3.74 (95% CI 2.67-5.24; α: 0.70)]. We noted a weaker positive association between transverse palmar crease [OR: 2.68 (95% CI 1.70-4.18; α: 0.51)], elongated face [OR: 3.69 (95% CI 2.84-4.81; α: 0.63)]; hyperextensible metacarpo-phalangeal joints [OR: 2.68 (95% CI 2.15-3.34; α: 0.57)] and the Fragile X syndrome. CONCLUSION: This study has identified the highest risk features for patients with Fragile X syndrome that have been used to design a universal clinical checklist.

Autosomal recessive primary microcephaly due to ASPM mutations: An update.

Autosomal recessive microcephaly or microcephaly primary hereditary (MCPH) is a genetically heterogeneous neurodevelopmental disorder characterized by a reduction in brain volume, indirectly measured by an occipitofrontal circumference (OFC) 2 standard deviations or more below the age- and sex-matched mean (-2SD) at birth and -3SD after 6 months, and leading to intellectual disability of variable severity. The abnormal spindle-like microcephaly gene (ASPM), the human ortholog of the Drosophila melanogaster "abnormal spindle" gene (asp), encodes ASPM, a protein localized at the centrosome of apical neuroprogenitor cells and involved in spindle pole positioning during neurogenesis. Loss-of-function mutations in ASPM cause MCPH5, which affects the majority of all MCPH patients worldwide. Here, we report 47 unpublished patients from 39 families carrying 28 new ASPM mutations, and conduct an exhaustive review of the molecular, clinical, neuroradiological, and neuropsychological features of the 282 families previously reported (with 161 distinct ASPM mutations). Furthermore, we show that ASPM-related microcephaly is not systematically associated with intellectual deficiency and discuss the association between the structural brain defects (strong reduction in cortical volume and surface area) that modify the cortical map of these patients and their cognitive abilities.

Sacrococcygeal teratoma in a female newborn with clinical features of trisomy 13: a case report from Central Africa.

INTRODUCTION: The objective of this report is to describe the first patient presenting clinical features of trisomy 13 in association with a sacrococcygeal teratoma. CASE PRESENTATION: We present the case of a Congolese female infant born with bilateral cleft lip and palate, hypotelorism, microcephaly, and capillary hemangioma on her face. She presented with a large sacrococcygeal mass (15.0 cm ×12.0 cm ×5.0 cm) with a cystic consistency and a positive transillumination. CONCLUSION: This observation suggests that overexpression of certain genes on chromosome 13 may lead to tumor formation from remnant cells of Hensen's node.

Mirror-image gastroschisis in monochorionic female twins.

We report a case of "mirror-image" gastroschisis in female monochorionic twins. One of the twins presents a right-sided gastroschisis, the other a left-sided gastroschisis. Both twins have anteriorly placed anus and sacral dimple. To the best of our knowledge, this represents the first case of mirror image or discordant left and right gastroschisis in monochorionic twins reported in the literature. This observation may shed further light on the pathogenesis of gastroschisis.