Re-focusing on Agnathia-Otocephaly complex

Dubucs, Charlotte; Chassaing, Nicolas; Sergi, Consolato; Aubert-Mucca, Marion; Attié‐Bitach, Tania; Lacombe, Didier; Thauvin‐Robinet, Christel; Arpin, Stéphanie; Perez, Marie José; Cabrol, Christelle; Chen, C.P.; Aziza, Jacqueline; Colin, Estelle; Martinovic, Jéléna; Calvas, Patrick; Plaisancie, Julie

doi:10.1007/s00784-020-03443-w

Cited by 8 publications

(9 citation statements)

References 59 publications

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“…In this research, a new PRRX1 loss-of-function variation was identified to give rise to AF and PDA, therefore expanding the phenotypic spectrum linked to PRRX1 and supporting PRRX1 as a causative gene for AF and CHD. Notably, heterozygous loss-of-function variations in PRRX1 have already been described in patients with agnathia-otocephaly complex, a rare condition characterized by mandibular hypoplasia or agnathia, ear anomalies (melotia/synotia) and microstomia with aglossia ( Dubucs et al , 2021 ). It is interesting that the same kind of variation has been associated with a quite different phenotype (AF) in the present study, which may be explained in part by the distinct genetic backgrounds.…”

Section: Discussionmentioning

confidence: 99%

A novel PRRX1 loss-of-function variation contributing to familial atrial fibrillation and congenital patent ductus arteriosus

Zhang

Guo

et al. 2022

Genet. Mol. Biol.

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Atrial fibrillation (AF) represents the most common type of sustained cardiac arrhythmia in humans and confers a significantly increased risk for thromboembolic stroke, congestive heart failure and premature death. Aggregating evidence emphasizes the predominant genetic defects underpinning AF and an increasing number of deleterious variations in more than 50 genes have been involved in the pathogenesis of AF. Nevertheless, the genetic basis underlying AF remains incompletely understood. In the current research, by whole-exome sequencing and Sanger sequencing analysis in a family with autosomal-dominant AF and congenital patent ductus arteriosus (PDA), a novel heterozygous variation in the PRRX1 gene encoding a homeobox transcription factor critical for cardiovascular development, NM_022716.4:c.373G>T;p.(Glu125 * ), was identified to be in co-segregation with AF and PDA in the whole family. The truncating variation was not detected in 306 unrelated healthy individuals employed as controls. Quantitative biological measurements with a reporter gene analysis system revealed that the Glu125 * -mutant PRRX1 protein failed to transactivate its downstream target genes SHOX2 and ISL1 , two genes that have been causally linked to AF. Conclusively, the present study firstly links PRRX1 loss-of-function variation to AF and PDA, suggesting that AF and PDA share a common abnormal developmental basis in a proportion of cases.

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Section: Discussionmentioning

confidence: 99%

A novel PRRX1 loss-of-function variation contributing to familial atrial fibrillation and congenital patent ductus arteriosus

Zhang

Guo

et al. 2022

Genet. Mol. Biol.

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“…This is why early prenatal diagnosis and patient information are so important, as termination of pregnancy could be an option. An additional difficulty in making the diagnosis of fetal otocephaly is the fact that it often cannot be confirmed by a genetic abnormality 2…”

Section: Discussionmentioning

confidence: 99%

“…It affects less than 1 in 70 000 newborns 1. About one-third of all genetically tested cases carry a mutation or deletion in the OTX2 or PRRX1 genes 2. In individual cases, the use of beclomethasone, theophylline and salicylates during pregnancy has been associated with otocephaly 3 4…”

Section: Introductionmentioning

confidence: 99%

Advances in prenatal diagnosis of fetal otocephaly by 3D imaging

Kinkel

Rduch²,

Abgottspon³

et al. 2022

BMJ Case Rep

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The case presented here shows the rare diagnosis of fetal otocephaly with lethal prognosis due to impossible airway management after birth. Otocephaly is characterised by fetal agnathia, microstomia and synotia. As in our case, otocephaly is usually not recognised until the third trimester and leads to challenging clinical situations and decision making.A woman in her 30s presented to our tertiary hospital at 27 weeks of gestation because of an unexplained polyhydramnios. 3D imaging illustrated the complex syndrome of otocephaly and helped understand the present disease patterns. After premature birth, palliative care was agreed on and the newborn was able to pass away peacefully in the arms of his parents.We recommend the implementation of 3D imaging into routine scans for the assessment of the fetal face and ears, especially in situations of unexplained polyhydramnios.

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“…The need for medical, catheterbased, or surgical therapy depends on the underlying anatomy, and a substantial proportion of morbidity and mortality among HTX patients is from cardiac disease [6]. [104] Bardet-Biedl Syndrome [105] Cardiac Urogenital Syndrome [106] Cardiofacioneurodevelopmental Syndrome [107] Carpenter Syndrome [108] DK Phocomelia Syndrome Ellis-Van Creveld Syndrome [109] Galactosialidosis Hennekam Lymphangiectasia-Lymphedema Syndrome [110] Johanssen-Blizzard Syndrome Cardiac anatomic assessment requires a detailed examination of thoraco-abdominal situs, cardiac position, atrial situs, ventricular looping, atrioventricular alignments and connections, ventricular-arterial alignments, infundibular anatomy, relationships between the semilunar valves and great arteries, septal defects, and anomalies of venous return and/or arterial exit, and atrial and ventricular septal defects [29,30]. The myocardial architecture should be assessed for non-compaction, which may predispose toward early or late cardiomyopathy [31].…”

Section: Cardiac Anatomymentioning

confidence: 99%

A multi-disciplinary, comprehensive approach to management of children with heterotaxy

Saba

Geddes

Ware

et al. 2022

Orphanet J Rare Dis

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Heterotaxy (HTX) is a rare condition of abnormal thoraco-abdominal organ arrangement across the left–right axis of the body. The pathogenesis of HTX includes a derangement of the complex signaling at the left–right organizer early in embryogenesis involving motile and non-motile cilia. It can be inherited as a single-gene disorder, a phenotypic feature of a known genetic syndrome or without any clear genetic etiology. Most patients with HTX have complex cardiovascular malformations requiring surgical intervention. Surgical risks are relatively high due to several serious comorbidities often seen in patients with HTX. Asplenia or functional hyposplenism significantly increase the risk for sepsis and therefore require antimicrobial prophylaxis and immediate medical attention with fever. Intestinal rotation abnormalities are common among patients with HTX, although volvulus is rare and surgical correction carries substantial risk. While routine screening for intestinal malrotation is not recommended, providers and families should promptly address symptoms concerning for volvulus and biliary atresia, another serious morbidity more common among patients with HTX. Many patients with HTX have chronic lung disease and should be screened for primary ciliary dyskinesia, a condition of respiratory cilia impairment leading to bronchiectasis. Mental health and neurodevelopmental conditions need to be carefully considered among this population of patients living with a substantial medical burden. Optimal care of children with HTX requires a cohesive team of primary care providers and experienced subspecialists collaborating to provide compassionate, standardized and evidence-based care. In this statement, subspecialty experts experienced in HTX care and research collaborated to provide expert- and evidence-based suggestions addressing the numerous medical issues affecting children living with HTX.

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Re-focusing on Agnathia-Otocephaly complex

Cited by 8 publications

References 59 publications

A novel PRRX1 loss-of-function variation contributing to familial atrial fibrillation and congenital patent ductus arteriosus

A novel PRRX1 loss-of-function variation contributing to familial atrial fibrillation and congenital patent ductus arteriosus

Advances in prenatal diagnosis of fetal otocephaly by 3D imaging

A multi-disciplinary, comprehensive approach to management of children with heterotaxy

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