Heterotaxy: Associated conditions and hospital-based prevalence in newborns

Abstract

Purpose: To provide insight into the possible etiology and prevalence of heterotaxy, we studied conditions associated with heterotaxy in a consecutive hospital population of newborns. Methods: From 1972 to March, 1999 (except February 16, 1972 to December 31, 1978, 5 8 cases of heterotaxy were ascertained from a cohort of 201,084 births in the ongoing Active Malformation Surveillance Program at the Brigham and Women's Hospital.This registry includes livebirths, stillbirths, and elective abortions. Prevalence among nontransfers (i.e., patients whose mothers had planned delivery at this hospital) was calculated as approximately 1 per 10,000 total births (20 of 201,084). Results: We analyzed a total of 5 8 patients consisting of 20 (34%) nontransfers and 3 8 (66%) transfers. Patients were categorized by spleen status as having asplenia (7 nontransfers, 25 total), polysplenia (8,20), right spleen (4, l l ) , normal left (0, I ) , and unknown (1, 0). Among the 20 nontransfer and 5 9 total heterotaxy patients, the following associated medical conditions were present: chromosome abnormality ( 1 nontransfer, 2 total), suspected Mendelian or chromosome microdeletion disorder (1 nontransfer, 6 total), and maternal insulindependent diabetes mellitus ( 1 nontransfer, 2 total). There were 6 twins ( 1 member each from 6 twin pairs including 1 dizygous, 4 monozygous, 1 conjoined; 2 were nontransfers). An associated condition occurred in 5 (25%) nontransfer and 1 6 (28%) total patients, or among 1 0 of 53 singleton births (19%). Conclusions: Although most cases of heterotaxy in this series were sporadic events, an associated condition was present in about one-fourth of the cases. Not all of these conditions would be considered causative etiologies. Based on this small series alone, maternal insulin-dependent diabetes cannot be viewed as a risk factor for heterotaxy. However, the specific association of diabetes with polysplenia with/without left atrial isomerism is noteworthy, and adds weight to animal and epidemiologic case-control data. Genetics in Medicine, 2000:2(3):157-172.Key Words: Asplenia, cardiovascular malformations, congenital heart defects, defects of right, left determination, genetic epidemiology, heterotaxy, isomerism, laterality defects, maternal diabetes, polysplenia, prevalence, situs ambiguous, situs inversus Errors in the development o f the normal right-left axis in humans can produce a variety o f laterality defects. The classification o f these complexes is most meaningful when information about the heart, lungs, cilia, spleen, and abdominal organs is combined. Classical heterotaxy refers t o abnormal abdominal and thoracic visceral situs, which may include the presence o f symmetry (i.e., right or left isomerism), ambiguous or inFront the 'Departrrrmt ofNpwborn klnircrnc, tlr~. Brtglrottr olld l\'otrrcn', Hosprml; tlrc-'Gcnetrcs and Terntolory Urrir, IJ~diatric Servrce, and 'Dn,rsrotr ufPediatrr<-Gtrdrolug) verted situs, abnormalities o f the spleen and complex cardiovascular malformations (CVM...

Heterotaxy syndrome: a case report

“…The loss of such orderly arrangement may characterize situs inversus or a disordered and variable arrangement (heterotaxy syndrome). Heterotaxy syndrome presents an approximate incidence of 1:10,000 births and is slightly more prevalent in men, at a ratio of 2:1 (3,5) .…”

Nodal Signaling and Congenital Heart Defects

“…Conditional deletion of Nodal in the lateral plate mesoderm in mice circumvents the early requirement for Nodal signaling during gastrulation and results in heterotaxy, a condition characterized by left-right ambiguity of thoracic and abdominal visceral organs [24]. These mice exhibit transposition of the great arteries of the heart, right-sided isomerism of the lungs, and right-sided stomach [25].…”

Molecular Genetic Analysis of CRELD1 in Patients with Heterotaxy Disorder

“…Heterotaxy accounts for approximately 3% of all congenital heart defects (CHD) with an approximate prevalence of 1:10,000 live births (Lin et al, 2000), most frequently diagnosed in the newborn mainly due to cyanotic congenital heart disease (Sutherland and Ware, 2009). In individuals with heterotaxy any internal organ that is asymmetrically positioned can be abnormal and the midline defect, which results from disclosure of neural tube, occurs in approximately 40% of patients (Zhu et al, 2006).…”

“…Situs ambiguous, which refers to abnormal arrangement of internal organs with discordance of thoracic and visceral anatomy is mainly characterized by congenital anomalies and is estimated to take place in 1:10,000 live births (Lin et al, 2000). Most cases of situs ambiguous occur sporadically and do not follow obvious Mendelian inheritance patterns, although phenotypic characterization of families suggests both autosomal recessive and dominant patterns with incomplete penetrance due to evidence of familial clustering.…”