Frontonasal Dysplasia (Frontorhiny) via the ALX3 Gene

ALX3-related frontonasal Dysplasia is inherited in an autosomal recessive inheritance pattern. The ALX3 protein is a member of homeobox 3 transcription factor family and particularly plays a critical role during facial development in humans. Only 7 homozygous pathogenic ALX3 variants have been reported in 7 families. They are: 4 missense (4), nonsense (1), splicing (1) and small deletion (1) (Twigg et al. 2009). All these variants are in the DNA binding domain of the ALX3 protein (Twigg et al. 2009).

Frontonasal Dysplasia, a malformation disorder of head and face, is mainly characterized by the combination of hypertelorism, corpus callosum, and malformed nose and lip palate. Malformed nose includes broad nasal root, lack of formation of the nasal tip and nasal cleft. Patients may also present ophthalmofrontonasal dysplsia with ear tags, anterior cranium bifidum occultum, and a V-shaped or widow's peak frontal hairline (Guion-Almeida et al. 1996; Twigg et al. 2009).

To date, in the only published study, ALX3 pathogenic variants were detected in all 7 studied families affected with Frontonasal Dysplasia (Twigg et al. 2009).

This test provides full coverage of all coding exons of the ALX3 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).