FrontorhinyQ75.-

Frontorhiny is one of the two forms of midface malformations characterized by ocular hypertelorism, broad and short nasal root, split nasal tip, broad nasal bridge, widely spaced slit-like nostrils, long broad philtrum, a notch in the midline of the upper lip and alveolus, and a V-shaped hairline(widow`s peak). Other recurrent features that occur in a minority of affected individuals are ptosis of the upper eyelid and dermoid cysts in the midline of the craniofacial structures. Frontorhinia syndrome is inherited in an autosomal recessive manner.

This is caused by sequence variants in the ALX3 gene (Aristaless-like homeobox 3). Numerous homozygous pathogenic mutations have now been identified. These mutations include missense substitutions at critical positions within the conserved homeodomain as well as nonsense, frameshift and splice site mutations, all of which lead to severe or complete loss of function.

ALX3 is essential for normal facial development in humans. A deficiency of ALX3 causes the clinically recognizable phenotype known as frontorhinia.

1. Twigg SR et al. (2009) Frontorhiny, a distinctive presentation of frontonasal dysplasia caused by recessive mutations in the ALX3 homeobox gene. Am J Hum Genet 84:698-705.
2. Ullah A et al. (2018) Exome sequencing revealed a novel nonsense variant in ALX3 gene underlying frontorhiny. J Hum Genet 63:97-100.