Heterotaxy, Visceral, 3, Autosomal

An autosomal form of visceral heterotaxy, designated HTX3, has been mapped to chromosome 6q21.

Description

Heterotaxy ('heter' meaning 'other' and 'taxy' meaning 'arrangement'), or situs ambiguus, is a developmental condition characterized by randomization of the placement of visceral organs, including the heart, lungs, liver, spleen, and stomach. The organs are oriented randomly with respect to the left-right axis and with respect to one another (Srivastava, 1997). Heterotaxy is a clinically and genetically heterogeneous disorder.

For a discussion of the genetic heterogeneity of visceral heterotaxy, see HTX1 (306955).

Clinical Features

Peeters et al. (2001) reported a patient in whom routine ultrasound examination at gestational age 28 weeks had shown atrioventricular septal defect and abdominal situs inversus. Postnatally, the patient was found to have mesocardia, atrioventricular septal defect with monoatrium (large atrial septal defect type I), and left atrial isomerism. The abdominal aorta was on the right side. The inferior vena cava was on the left side. The liver was on the left, the stomach and spleen on the right, and intestinal malrotation was present.

Cytogenetics

Kato et al. (1996, 1997) described heterotaxy in association with a de novo balanced translocation involving 6q21 and 18q21.3 (or q22).

In a patient with heterotaxy, Peeters et al. (2001) described a de novo, apparently balanced reciprocal translocation with breakpoints at 6q21 and 20p13. The breakpoints on 6q21 in both patients were located in the same chromosomal region spanning maximally 2 Mb. Peeters et al. (2001) speculated that the 2 breakpoints led to disruption of the function of a single gene, either directly or through long distance effects.

Molecular Genetics

Associations Pending Confirmation

In the patient with heterotaxia and a de novo reciprocal translocation, t(6;18)(q21;q21), reported by Kato et al. (1996), Peeters et al. (2003) found that the PA26 gene (SESN1; 606103) was disrupted by the 6q21 breakpoint. Northern blot analysis showed decreased expression of the PA26 gene in an Epstein-Barr virus-transformed cell line from this patient. Mutation analysis of the PA26 gene in 40 unrelated individuals with unexplained heterotaxia failed to identify mutations, indicating that PA26 mutations are not a frequent cause of heterotaxia.