Home > D. Systemic pathology > Genetic and developmental anomalies > familial heterotaxy
familial heterotaxy
Wednesday 25 July 2007
Familial presentation of Left–Right anomalies (heterotaxies) occurs in less than 5% of cases. However one should also take into account the familial occurrence of isolated congenital heart defects not associated with other features of a situs defect. For instance, isolated TGA or DORV can result from mutations in the CRYPTIC gene.
Types
autosomal dominant heterotaxy
In all pedigrees with dominant inheritance, there is evidence for variable expression and non-penetrance. Non-penetrance was further illustrated in some families by the presence of the same mutation in one of the unaffected parents of patients with mutations in the ACVR2B gene or the CRYPTIC gene. For this reason, the risk of laterality defects appears to be less than the risk of transmission of the mutant allele. This probably also reflects a multifactorial or polygenic cause in most cases of sporadic heterotaxia.
autosomal recessive heterotaxy
X-linked heterotaxy
If an X-linked inheritance is suspected, mutation analysis for the ZIC3 gene is recommended. In half of the families with X-linked inheritance of heterotaxia, a ZIC3 mutation can be identified.ZIC3 has been identified by linkage analysis of a large family with X-linked heterotaxia. The cloning of the ZIC3 gene was facilitated through the finding of a small 0.6–1.1 Mb deletion on Xq26.2 in a familial case. Final proof for its role in heterotaxia was obtained by mutation analysis in other patients.
See also
heterotaxies
- sporadic heterotaxy
References
Peeters H, Devriendt K. Human laterality disorders. Eur J Med Genet. 2006 Sep-Oct;49(5):349-62. PMID: 16461029