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

Abstract

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.

Keywords: Asplenia; Congenital heart disease; Heterotaxy; Laterality disorder.

Fig. 1

Variations of atrial appendage isomerism. Adapted from Jacobs et al. [8]. LA left atrium, LAA left atrial appendage, RA right atrium, RAA right atrial appendage. Four possible variations of right (triangular) and left (tubular) atrial appendages including the usual arrangement (A), mirror-imaged arrangement (B), right atrial appendage isomerism (C), and left atrial appendage isomerism (D)

Fig. 2

Classification of genetic etiologies of heterotaxy. AD autosomal dominant, AR autosomal recessive, BBS Bardet Biedl syndrome, PCD primary ciliary dyskinesia, XL X-linked

Fig. 3

Algorithm for management of fever in a patient with asplenia or functional hyposplenism. Modified from Loomba et al. [56]. IV intravenous, IM intramuscular

Fig. 4

Variations of intestinal rotation. Three variations of intestinal rotation including normal fixation of the duodenojejunal junction (DJ) in the left upper quadrant and cecum (Ce) in the right lower quadrant (A), complete malrotation with duodenojejunal junction and cecum in close proximity leading to a narrow mesentery (B) and heterotaxy in which the location of the duodenojenunal junction and cecum is not normal but the mesentery is not as narrow as complete malrotation (C)