Prevalence and phenotypes associated with ALPK3 null variants in a large French multicentric cohort: Confirming its involvement in hypertrophic cardiomyopathy.

Biallelic disease-causing variants in the ALPK3 gene were first identified in children presenting with a severe cardiomyopathy. More recently, it was shown that carriers of heterozygous ALPK3 null variants are at risk of developing hypertrophic cardiomyopathy (HCM) with an adult onset. Since the number of reported ALPK3 patients is small, the mutational spectrum and clinical data are not fully described. In this multi-centric study, we described the molecular and clinical spectrum of a large cohort of ALPK3 patients. Genetic testing using targeted next generation sequencing was performed in 16 183 cardiomyopathy index cases. Thirty-six patients carried at least one null ALPK3 variant. The five paediatric patients carried two ALPK3 variants, all presented an HCM phenotype with severe outcomes (one transplantation, one heart failure and one cardiac arrest). The 31 adult patients carried heterozygous variants and the main phenotype was HCM (n = 26/31); including 15% (n = 4) presented with an apical or a concentric form of hypertrophy. Reporting a large cohort of ALPK3 patients, this collaborative work confirmed a strong association with HCM and suggesting his screening in the context of idiopathic HCM.

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.

Management and outcomes of pregnant women with cardiovascular diseases in a cardio-obstetric team.

BACKGROUND: Cardiovascular diseases (CVDs) are currently the leading cause of maternal death in Western countries. Although multidisciplinary cardio-obstetric teams are recommended to improve the management of pregnant women with CVD, data supporting this approach are scarce. AIMS: To describe the characteristics and outcomes of pregnant patients with CVD managed within the cardio-obstetric programme of a tertiary centre. METHODS: We included every pregnant patient with history of CVD managed by our cardio-obstetric team between June 2017 and December 2019, and collected all major cardiovascular events (death, heart failure, acute coronary syndromes, stroke, endocarditis and aortic dissection) that occurred during pregnancy, peripartum and the following year. RESULTS: We included 209 consecutive pregnancies in 202 patients. CVDs were predominantly valvular heart diseases (37.8%), rhythm disorders (26.8%), and adult congenital heart diseases (22.5%). Altogether, 47.4% were classified modified World Health Organization (mWHO)>II, 66.5% had CARdiac disease in PREGnancy score (CARPREG II)≥2 and 80 pregnancies (38.3%) were delivered by caesarean section. Major cardiovascular events occurred in 16 pregnancies (7.7%, 95% confidence interval [CI] 4.5-12.2) during pregnancy and in three others (1.5%, 95% CI 0.3-4.1) during 1-year follow-up. Most events (63.1%) occurred in the 16.3% of patients with unknown CVD before pregnancy. CONCLUSIONS: The management of pregnant patients with CVD within a cardio-obstetric team seems encouraging as we found a relatively low rate of cardiovascular events compared to the high-risk profile of our population. However, most of the remaining events occurred in patients without cardiac monitoring before pregnancy.