Craniosynostosis and Dental Anomalies, Autosomal Recessive Crouzon-like Craniosynostosis via the IL11RA Gene

Craniosynostosis is a primary abnormality of skull growth involving premature fusion of the cranial sutures causing skull deformity. IL11RA pathogenic variants cause craniosynostosis, maxillary hypoplasia, and dental anomalies, including malocclusion, delayed and ectopic tooth eruption, and/or supernumerary teeth (Nieminen et al. 2011). IL11RA variants also cause autosomal recessive Crouzon-like craniosynostosis or Pansynostosis (Keupp et al. 2013).

IL11RA related disorders are inherited in an autosomal recessive manner. The IL11RA protein encoded by the IL11RA gene is a stromal cell-derived cytokine that belongs to a family of pleiotropic and redundant cytokines. Approximately 10 unique IL11RA pathogenic variants have been reported in two unrelated studies (Nieminen et al. 2011; Keupp et al. 2013). They include missense, splicing, truncation, and small deletion/insertion (Nieminen et al. 2011; Keupp et al. 2013, Human Gene Mutation Database). No large deletions/duplications have been reported to date.

Due to limited cases and publications, the clinical sensitivity related to IL11RA testing is hard to predict. Pathogenic IL11RA variants were reported in five families with an initial clinical diagnosis of Crouzon syndrome, pansynostosis, or unclassified syndromic craniosynostosis (Keupp et al. 2013).

To date, no large deletions or duplications have been reported in IL11RA.

This test provides full coverage of all coding exons of the IL11RA gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).