Genetic Disturbances in Patients with Bodily Isomerism from a Single Center: Clinical Implications of Affected Genes and Potential Impact of Ciliary Dyskinesia

Abstract

So-called heterotaxy or isomerism is characterized by abnormal lateralization and malformations of the bodily organs. The mechanism is unclear, although there is growing evidence that ciliary dyskinesia is involved. We reviewed genetic findings from patients with isomerism to determine if affected genes were known to be associated with isomerism and ciliary dyskinesia and determine associations between genotype and clinical findings. We identified patients with isomerism cared for over a 16-year period. Characteristics were compared between those with and without identified mutations. A total of 83 patients with isomerism were identified. Of those who had genotyping, 14/27 had mutations identified, most frequently involving the CFC1 and NODAL genes. Specific mutations were associated with clinical findings, with NODAL mutations often portending need for increased clinical support. Genes associated with isomerism and/or ciliary dyskinesia were identified in the cohort. Specific gene mutations may help predict clinical course.

A Rare Case of Polysplenia Syndrome Associated with Severe Cardiac Malformations and Congenital Alveolar Dysplasia in a One-Month-Old Infant: A Complete Macroscopic and Histopathologic Study

“…Mutation in the CFC1 gene, encoding a component of the multi-subunit receptor for NODAL , is a particularly good candidate for the broad spectrum of phenotypic changes, such as polysplenia, complex cardiac anomalies, left isomerism of lungs, bilateral superior vena cava, midline liver, right-sided stomach, and intestinal malrotation, as we have described here [ 30 ]. CFC1 mutation have also been found in 80% of cases with left isomerism according to Loomba et al, while NODAL mutation was more consistent with right isomerism [ 31 ]. Overall, the exact genetic mechanism that triggers polysplenia syndrome is still largely unknown, requiring more frequent diagnosis of ante- or post-mortem cases.…”

Heterotaxy – Res ipsos loquitur

“…6,7 Involvement of specific genes also has been demonstrated, clinically, to be implicated more often in either right or left isomerism. 8 Thus, the genetic underpinnings seem to indicate that isomerism, and not heterotaxy, better discriminates the entities by their potential genetic perturbations. It is these genetic cues that seem to be responsible for the production of isomeric as opposed to lateralised features.…”