AI Article Synopsis

  • Heterozygous mutations in the ALX4 and MSX2 genes lead to skull defects known as enlarged parietal foramina (PFM) and cranium bifidum (CB), with their specific contributions to these conditions not fully understood.
  • In a study analyzing 11 new PFM/CB cases, 181 craniosynostosis (CRS) cases, and a family with a deletion affecting ALX4, researchers identified mutations in ALX4 and MSX2 in several patients, particularly in familial instances.
  • Although mutations in ALX4 and MSX2 have similar prevalence rates and result in indistinguishable clinical features, specific mutations like ALX4 p.R218Q are linked

Article Abstract

Heterozygous mutations of the homeobox genes ALX4 and MSX2 cause skull defects termed enlarged parietal foramina (PFM) and cranium bifidum (CB); a single MSX2 mutation has been documented in a unique craniosynostosis (CRS) family. However, the relative mutational contribution of these genes to PFM/CB and CRS is not known and information on genotype-phenotype correlations is incomplete. We analysed ALX4 and MSX2 in 11 new unrelated cases or families with PFM/CB, 181 cases of CRS, and a single family segregating a submicroscopic deletion of 11p11.2, including ALX4. We explored the correlations between skull defect size and age, gene, and mutation type, and reviewed additional phenotypic manifestations. Four PFM cases had mutations in either ALX4 or MSX2; including previous families, we have identified six ALX4 and six MSX2 mutations, accounting for 11/13 familial, but only 1/6 sporadic cases. The deletion family confirms the delineation of a mental retardation locus to within 1.1 Mb region of 11p11.2. Overall, no significant size difference was found between ALX4- and MSX2-related skull defects, but the ALX4 mutation p.R218Q tends to result in persistent CB and is associated with anatomical abnormalities of the posterior fossa. We conclude that PFM caused by mutations in ALX4 and MSX2 have a similar prevalence and are usually clinically indistinguishable. Mutation screening has a high pickup rate in PFM, especially in familial cases, but is not indicated in CRS.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1477589PMC
http://dx.doi.org/10.1038/sj.ejhg.5201526DOI Listing

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