Abstract
Abstract Objectives Agnathia-otocephaly complex (AOC) is an extremely rare, lethal disorder causing obstruction of the upper airway at birth due to absence of the mandible and hypoplasia of the oral cavity. Implications for future pregnancies need to be elucidated by parental counselling, as recurrence of AOC or associated comorbidities are possible. Very little is known on this subject, because of the rarity of the disorder and scarce data on genetic causes of this complex. The objectives of this study were to determine the recurrence risk and mode of inheritance for AOC based on current literature. Contents Recurrence of AOC or associated comorbidities within the family of an index case was reported in eight articles, describing 7 and 27 relatives, respectively. There were eight AOC cases in which the genetic cause was known. Mutations in 2 genes, orthodenticle homeobox 2 (OTX2) and paired related homeobox 1 (PRRX1), have been described. Due to its mainly sporadic appearance, recurrence risk is low. Counselling on recurrence risk is difficult, because of a broad heterogeneity with complex inheritance patterns and variability in phenotypic expression. Outlook Chromosomal analysis and exome sequencing in children with AOC will help unravel current aetiological uncertainties and could help in further reproductive decisions. We emphasize the need for timely diagnosis through ultrasound, providing parents with the opportunity to receive multidisciplinary counselling, giving them the chance to contemplate their management decisions.
Highlights
Agnathia-otocephaly complex (AOC) is an exceptionally uncommon congenital developmental defect
As a definition of AOC, we used the presence of the clinical triad of mandibular hypoplasia/ agnathia, microstomia and melotia/synotia
Results of mutation analysis for paired related homeobox 1 (PRRX1) and orthodenticle homeobox 2 (OTX2) in respectively three and four other AOC patients remained negative [12, 16,17,18]. This suggests that mutations in these two genes can only partially explain the aetiology of the pathology
Summary
Agnathia-otocephaly complex (AOC) is an exceptionally uncommon congenital developmental defect. It is marked by (1) hypoplasia or absence of the mandible (agnathia), (2) underdevelopment of the oral orifice (microstomia) and (3) ventral and horizontal positioning of the ears (melotia) with or without midline fusion (synotia). This triad results in an obstruction of the upper airway, with a high risk of mortality. Prenatal diagnosis by ultrasound is possible; often the pathology is only recognized late during pregnancy, leaving parents in pressing need of guidance in informed decision making [1]. Information on the topic of the aetiology and recurrence risk is scant, rendering counselling difficult
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