Agnathia-Otocephaly Complex via the PRRX1 Gene

Agnathia-otocephaly complex (AGOTC, OMIM 202650) is a rare malformation disorder that probably occurs early in embryogenesis (Schiffer, C. et al. Am J Med Genet 112(2): 203-208, 2002). Mandibular hypoplasia or agnathia and abnormal ear position or ear fusion are the hallmark findings. Other findings include cleft palate, hypotelorism, microstomia, and the tongue can be small or absent. Variable findings include pulmonary hypoplasia and genitourinary and cardiovascular anomalies. Holoprosencephaly and situs inversus are commonly found in affected infants. Prenatal ultrasound has detected an affected fetus with polyhydramnios, micrognathia, low-set ears, and malformed feet (Schiffer, C. et al., 2002). Affected babies have been reported to die in utero or shortly after birth.

Agnathia-otocephaly complex is an autosomal dominant disorder. One case of familial recurrence due to paternal gonadal mosaicism has been reported (Dasouki, M. et al. Am J Med Genet 161(4): 803-808, 2013). De novo inheritance of a PRRX1 mutation has also been proven (Donnelly, M. et al. Prenat Diagn 32(9): 903-905, 2012).

Clinical and analytical sensitivity are unknown due to the rarity of this disorder.

This test provides full coverage of all coding exons of the PRRX1 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).