Prenatal exome sequencing, a powerful tool for improving the description of prenatal features associated with genetic disorders.

OBJECTIVE: Prenatal exome sequencing (pES) is now commonly used in clinical practice. It can be used to identifiy an additional diagnosis in around 30% of fetuses with structural defects and normal chromosomal microarray analysis (CMA). However, interpretation remains challenging due to the limited prenatal data for genetic disorders. METHOD: We conducted an ancillary study including fetuses with pathogenic/likely pathogenic variants identified by trio-pES from the "AnDDI-Prenatome" study. The prenatal phenotype of each patient was categorized as typical, uncommon, or unreported based on the comparison of the prenatal findings with documented findings in the literature and public phenotype-genotype databases (ClinVar, HGMD, OMIM, and Decipher). RESULTS: Prenatal phenotypes were typical for 38/56 fetuses (67.9%). For the others, genotype-phenotype associations were challenging due to uncommon prenatal features (absence of recurrent hallmark, rare, or unreported). We report the first prenatal features associated with LINS1 and PGM1 variants. In addition, a double diagnosis was identified in three fetuses. CONCLUSION: Standardizing the description of prenatal features, implementing longitudinal prenatal follow-up, and large-scale collection of prenatal features are essential steps to improving pES data interpretation.

Expanded phenotypic spectrum of UDP-glucose-6-dehydrogenase recessive neurodevelopmental disorder: Two novel descriptions with or without epileptic encephalopathy.

Recent advances in the understanding of infantile developmental epileptic encephalopathies (IDEE) have revealed the association of biallelic pathogenic variants in UGDH. In this study, we report two novel combinations identified by exome sequencing: p.(Arg135Trp) with p.(Arg65*) and p.(Arg102Trp) with p.(Arg65*). Both combinations share a common pathogenic nonsense variant, with the missense variants strategically located in the NAD-binding domain of the UGDH protein, predicted in structural models to create new interactions with the central domain. The first patient exhibited the typical UGDH-related disease phenotype and progressive microcephaly, a rarely reported feature. In contrast, the second patient presented an atypical phenotype, including absence of seizure, severe intellectual disability, ataxic gait, and abnormal eye movements. This comprehensive analysis extends the phenotypic spectrum of UGDH syndrome beyond early infantile intractable encephalopathy to include intellectual disability without epilepsy.

Pain Assessment in the Outpatient Pediatric Burn Patient: An Integrative Review.

BACKGROUND: There is no standardized practice in pediatric pain assessment with burn injuries in the outpatient clinic setting. OBJECTIVE: This review aims to identify reliable, validated tools to measure pain in the pediatric burn clinic population. METHODS: The literature search for this integrative review was conducted using the databases of PubMed, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Cochrane, and Embase from 2011 to 2023. Quality and relevance were appraised using the Johns Hopkins Nursing Evidence-Based Practice Model. Reporting was done according to a Preferred Reporting Items for Systemic Reviews and Meta-Analysis checklist. RESULTS: Fourteen articles and two clinical practice guidelines met inclusion criteria and were included in this review. CONCLUSION: The Pain Observation Scale for Young Children and the COMFORT Behavior Scale tools have shown good reliability and construct validity and can be safely used to measure background and procedural pain in daily burn practice. Further research on reliable, validated pain assessment techniques in the pediatric burn population is needed.

Primary Failure of Dental Eruption Due to Variants Parathyroid Hormone Receptor 1: Retrospective Study and Proposal of Guidelines Treatment.

OBJECTIVE: Primary failure of eruption is characterized by a nonsyndromic defect in tooth eruption in the absence of mechanical obstruction. It is correlated to rare heterozygous variants in the parathyroid hormone receptor 1 gene. The management of primary failure of eruption is complex because many therapies are ineffective. The present study aimed to compare the clinical outcomes of our patients with the findings reported in the literature, and to propose a treatment guideline based on the literature and our experience. METHODS: Retrospective study of patients affected by primary dental eruption failure in the department and analyse of the results and compare with those of the litterature. RESULTS: Twelve patients belonging to 5 families (9 males, 3 females; 13-52 y old) diagnosed and treated in the maxillofacial surgery and stomatology department of the Lille University Hospital were included. All patients showed posterior tooth involvement, and most patients showed bilateral defects. None of the affected teeth had coronal alveolar bone, whereas 6 patients showed root resorption in the affected teeth. Genetic analyses, performed on 11 patients, identified a parathyroid hormone receptor 1 disease-causing variant in 7 of them (63%). Multidisciplinary treatment was required to rehabilitate these patients. Orthodontic interventions, even at an early age, are difficult in affected teeth, which are often blocked or have internal resorption. Moreover, retention of these affected teeth during growth leads to dentoskeletal malocclusions, requiring difficult surgical management in the long term. Therefore, early extraction of these teeth is frequently recommended once the diagnosis has been confirmed. An implant-borne prosthetic rehabilitation can then be achieved at the end of growth after correction of the jaw discrepancy. In case of a late diagnosis, other surgical or noninvasive techniques may be used depending on the clinical situation. Distraction osteogenesis or segmental osteotomy could be discussed for patients with mild phenotypes. CONCLUSIONS: Early diagnosis of primary eruption defects is crucial to offer appropriate management as early as possible, and so to avoid late complicated treatments.

Delineation of the adult phenotype of Coffin-Siris syndrome in 35 individuals.

Coffin-Siris syndrome (CSS) is a rare multisystemic autosomal dominant disorder. Since 2012, alterations in genes of the SWI/SNF complex were identified as the molecular basis of CSS, studying largely pediatric cohorts. Therefore, there is a lack of information on the phenotype in adulthood, particularly on the clinical outcome in adulthood and associated risks. In an international collaborative effort, data from 35 individuals ≥ 18 years with a molecularly ascertained CSS diagnosis (variants in ARID1B, ARID2, SMARCA4, SMARCB1, SMARCC2, SMARCE1, SOX11, BICRA) using a comprehensive questionnaire was collected. Our results indicate that overweight and obesity are frequent in adults with CSS. Visual impairment, scoliosis, and behavioral anomalies are more prevalent than in published pediatric or mixed cohorts. Cognitive outcomes range from profound intellectual disability (ID) to low normal IQ, with most individuals having moderate ID. The present study describes the first exclusively adult cohort of CSS individuals. We were able to delineate some features of CSS that develop over time and have therefore been underrepresented in previously reported largely pediatric cohorts, and provide recommendations for follow-up.