Heterotaxy, Visceral, 4, Autosomal

A number sign (#) is used with this entry because visceral heterotaxy-4 (HTX4) is caused by heterozygous mutation in the ACVR2B gene (602730).

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

Kosaki et al. (1999) reported 3 unrelated patients with left-right axis malformations. The first patient had ventricular inversion (dextrocardia), but intact ventricular septum and normally related great arteries. The patient also had a right aortic arch and a right-sided spleen, as well as anomalies of the inferior and the superior vena cava. The second patient had a complete atrial ventricular canal defect with dextro-transposed great arteries and obstruction to pulmonary outflow. Pulmonary venous return was normal, but like the first patient, there was an interrupted inferior vena cava with azygous continuation. This patient also had polysplenia and midline liver. The third patient had ventricular inversion with ventricular septal defect, inversion and transposition of the great vessels, pulmonary stenosis, total anomalous pulmonary venous return, and midline liver.

Molecular Genetics

In 3 unrelated patients with left-right axis malformations, Kosaki et al. (1999) identified heterozygous mutations in the ACVR2B gene (602730.0001-602730.0002).

Animal Model

Oh and Li (1997) found that targeted disruption of the mouse Acvr2b gene results in abnormal left-right (LR) axis development in Acvr2b -/- homozygotes. Resulting malformations include atrial and ventricular septal defects, right-sided morphology of the left atrium and left lung, and spleen hypoplasia.