François Petit

The ABC and ACMG variant classification systems were compared by asking mainly European clinical laboratories to classify variants in 10 challenging cases using both systems, and to state if the variant in question would be reported as a relevant result or not as a measure of clinical utility. In contrast to the ABC system, the ACMG system was not made to guide variant reporting but to determine the likelihood of pathogenicity. Nevertheless, this comparison is justified since the ACMG class determines variant reporting in many laboratories. Forty-three laboratories participated in the survey. In seven cases, the classification system used did not influence the reporting likelihood when variants labeled as “maybe report” after ACMG-based classification were included. In three cases of population frequent but disease-associated variants, there was a difference in favor of reporting after ABC classification. A possible reason is that ABC step C (standard variant comments) allows a variant to be reported in one clinical setting but not another, e.g., based on Bayesian-based likelihood calculation of clinical relevance. Finally, the selection of ACMG criteria was compared between 36 laboratories. When excluding criteria used by less than four laboratories (<10%), the average concordance rate was 46%. Taken together, ABC-based classification is more clear-cut than ACMG-based classification since molecular and clinical information is handled separately, and variant reporting can be adapted to the clinical question and phenotype. Furthermore, variants do not get a clinically inappropriate label, like pathogenic when not pathogenic in a clinical context, or variant of unknown significance when the significance is known.

Increasing interest regarding neurodevelopmental disorders and democratization of chromosomal microarray analysis have led to growing identification of neuro-susceptibility copy number variations (CNVs). These CNVs have incomplete penetrance and variable expressivity (PIEV), which makes phenotypic features hard to predict. The French Consortium "AchroPuce" has provided a list of 17 CNVs that should be considered as PIEV CNVs. This list led to consensual French practices of healthcare professionals in postnatal diagnosis. However, no consensus was established in prenatal diagnosis and fetal pathology. 121 French health professionals were surveyed their opinions and practices regarding reporting of PIEV CNVs to patients, in order to identify key points so as to establish French recommendations. The survey showed that professionals in favor of reporting PIEV CNVs to patients in prenatal diagnosis and fetal pathology (respectively, 76% and 84% of respondents) considered highlighted that multidisciplinary consultation is the main point-of-care management before family survey. This statement is close to recommendations published worldwide. As a consequence, multidisciplinary expertise should be the basis of French recommendations concerning the reporting of PIEV CNVs and genetic counseling in prenatal diagnosis and fetal pathology.

This research has two objectives: (I) to improve the methodology of using small-sized iron slag (microslag) as a stratigraphic marker to reconstruct the centennial-scale floodplain evolution and (II) to study the geomorphic evolution of the Ardennian rivers using the evaluation of the concentration of microslag in alluvia. In addition, 14C dating, topographic surveys and sedimentological analysis were carried out. Using these data, floodplain processes have been quantified in several Belgian rivers (Ardennes massif): fine floodplain sedimentation, lateral mobility rates and channel incision phases. A major hillslope erosion episode occurred during the Bronze Age. Archaeological data and historical sources indicate Roman and High Middle Age occupations in the area but no evidence of erosion or increased floodplain sedimentation have been observed. Several peat layers have been dated in the Chavanne floodplain to approximately 1000 BP and probably indicate very low anthropogenic activity and a high level of groundwater. Before 1000 CE, the fluvial style of the Ardennian rivers was probably different, characterized by a low-level forested floodplain, which explains the presence of frequent peat layers within the alluvial sequences and abandoned channels. From the eleventh century onwards, a generalized increase in sedimentation rates occurred, coinciding with a higher concentration of charcoal in the alluvium and also the formation of colluvial deposits. Analyses of slag concentrations allowed us to reconstruct the evolution of the floodplain topography. In Ardennian rivers, the mean floodplain aggradation over the last several centuries is between 3 and 20 cm/century, depending on the study site. Such differences in floodplain sedimentation rates can be explained by several factors such as the distance to past cultivation areas, the degree of woodland clearance, flow velocities during floods and the incision of the riverbed during last centuries, which reduces the frequency of inundation and, therefore, sedimentation on floodplains.

Significant hydrological and morphological changes occur with the construction of hydropower plants. The main modifications are related to changes in the hydrological regime and disturbances of the sediment continuity.This study is based on the Warche River in the northern Ardennes (Belgium), on a 7 km stretch downstream of the Bütgenbach dam built in 1932. During the winter months, the hydroelectric power plants release a flow of 10m³/s almost every day, which corresponds to the morphogenic flow (0.6 bankfull discharge).A study carried out in the 1990s (Assani and Petit, 1997) showed that, following the construction of the Bütgenbach dam, a general incision of the entire 7 km stretch took place in about 30 years, followed by a doubling of the channel width. Other changes such as a reduction in the number of riffles and pools, an increase in the number of gravel banks and islands and an increase in rock outcrops in the channel have also taken place.In our study, the question is to quantify the rate of propagation of this incision. For this purpose, RFID tags implanted in pebbles were used. As the morphogenic discharge is reached almost daily, surveys were conducted directly in the days following the deployment of the PIT tags. In a second step, more spaced surveys were also carried out according to the hydrological events.A second part of our study consists of analysing the morphological evolution since the 1990s by comparing past surveys with the topographic data of 2022. Thanks to these data, we can observe whether a new morphological equilibrium has been reached or whether the canal continues to widen.

Background: Permanent aesthetic augmentation of the gluteal region can be achieved with fat graft and/or implants. Implant-based augmentations have been proposed since the late 1960s. Buttock implants can be placed in four different planes according to distinct surgical techniques: subcutaneous, subfascial, intramuscular, and submuscular. Methods: In this retrospective analysis, a 100 case series of patients seeking volume and shape amelioration of the gluteal region were studied. All of them had primary gluteoplasty performed with a submuscular implant placement by first author (F.P.) with a new technique, as described in the article. Results: Data on surgery time, implant volume selection, and postoperative complications were collected. The most frequent complications were delayed healing of the incision and implant flipping. Conclusions: Submuscular implant positioning is a safe and reliable technique for buttock augmentation with implants. Whatever the implant volume, submuscular gluteal augmentation carries the benefit of perfectly covering, protecting, and hiding the implant, making it almost impalpable and invisible. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

First trimester ultrasound screening is an essential fetal examination performed generally at 11–13 weeks of gestation (WG). However, it does not allow for an accurate description of all fetal organs, partly due to their development in progress. Meanwhile, increased nuchal translucency (INT) is a widely used marker known to be associated with chromosomal deleterious rearrangements. We report on a 14 WG fetus with an association of INT and univentricular congenital heart malformation (CHM) leading to chorionic villous sampling (CVS). Cytogenetic investigations performed using array‐Comparative Genomic Hybridization (CGH) and fluorescence in situ hybridization (FISH) demonstrated a 1.17 Mb deletion in 16q24.1 encompassing FOXF1 arisen de novo on maternal inherited chromosome. Fetopathological study confirmed CHM with hypoplastic left heart syndrome (HLHS) associating aortic atresia, mitral stenosis, and left ventricular hypoplasia and revealed in addition specific lung lesions corresponding to alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV). This is so far the first case of first trimester prenatal diagnosis of ACDMPV due to the deletion of FOXF1 gene. An interpretation of the complex genomic data generated by ultrasound markers is facilitated considerably by the genotype–phenotype correlations on fetopathological examination.

Metabolic myopathies comprise a diverse group of inborn errors of intermediary metabolism affecting skeletal muscle, and often present clinically as an inability to perform normal exercise. Our aim was to use the maximal mechanical performances achieved during two functional tests, isometric handgrip test and cycloergometer, to identify metabolic myopathies among patients consulting for exercise-induced myalgia. Eighty-three patients with exercise-induced myalgia and intolerance were evaluated, with twenty-three of them having a metabolic myopathy (McArdle, n = 9; complete myoadenylate deaminase deficiency, n = 10; respiratory chain deficiency, n = 4) and sixty patients with non-metabolic myalgia. In all patients, maximal power (MP) was determined during a progressive exercise test on a cycloergometer and maximal voluntary contraction force (MVC) was assessed using a handgrip dynamometer. The ratio between percent-predicted values for MVC and MP was calculated for each subject (MVC%pred:MP%pred ratio). In patients with metabolic myopathy, the MVC%pred:MP%pred ratio was significantly higher compared to non-metabolic myalgia (1.54 ± 0.62 vs. 0.92 ± 0.25; p < 0.0001). ROC analysis of MVC%pred:MP%pred ratio showed AUC of 0.843 (0.758–0.927, 95% CI) for differentiating metabolic myopathies against non-metabolic myalgia. The optimum cutoff was taken as 1.30 (se = 69.6%, sp = 96.7%), with a corresponding diagnostic odd ratio of 66.3 (12.5–350.7, 95% CI). For a pretest probability of 15% in our tertiary reference center, the posttest probability for metabolic myopathy is 78.6% when MVC%pred:MP%pred ratio is above 1.3. In conclusion, the MVC%pred:MP%pred ratio is appropriate as a screening test to distinguish metabolic myopathies from non-metabolic myalgia.

Metabolic myopathies are muscle disorders caused by a biochemical defect of the skeletal muscle energy system resulting in exercise intolerance. The primary aim of this research was to evaluate the oxygen cost (∆V’O₂/∆Work-Rate) during incremental exercise in patients with metabolic myopathies as compared with patients with non-metabolic myalgia and healthy subjects. The study groups consisted of eight patients with muscle glycogenoses (one Tarui and seven McArdle diseases), seven patients with a complete and twenty-two patients with a partial myoadenylate deaminase (MAD) deficiency in muscle biopsy, five patients with a respiratory chain deficiency, seventy-three patients with exercise intolerance and normal muscle biopsy (non-metabolic myalgia), and twenty-eight healthy controls. The subjects underwent a cardiopulmonary exercise test (CPX Medgraphics) performed on a bicycle ergometer. Pulmonary V’O₂ was measured breath-by-breath throughout the incremental test. The ∆V’O₂/∆Work-Rate slope for exercise was determined by linear regression analysis. Lower oxygen consumption (peak percent of predicted, mean ± SD; p < 0.04, one-way ANOVA) was seen in patients with glycogenoses (62.8 ± 10.2%) and respiratory chain defects (70.8 ± 23.3%) compared to patients with non-metabolic myalgia (100.0 ± 15.9%) and control subjects (106.4 ± 23.5%). ∆V’O₂/∆Work-Rate slope (mLO₂.min⁻¹.W⁻¹) was increased in patients with MAD absent (12.6 ± 1.5), MAD decreased (11.3 ± 1.1), glycogenoses (14.0 ± 2.5), respiratory chain defects (13.1 ± 1.2), and patients with non-metabolic myalgia (11.3 ± 1.3) compared with control subjects (10.2 ± 0.7; p < 0.001, one-way ANOVA). In conclusion, patients with metabolic myopathies display an increased oxygen cost during exercise and therefore can perform less work for a given VO₂ consumption during daily life-submaximal exercises.