Further delineation of the oculoauricular syndrome phenotype: A new family with a novel truncating HMX1 mutation

Ophthalmic Genet. 2018 Apr;39(2):215-220. doi: 10.1080/13816810.2017.1401089. Epub 2017 Nov 15.


Biallelic HMX1 mutations cause a very rare autosomal recessive genetic disorder termed as oculoauricular syndrome (OAS) because it is characterized only by the combination of eye and ear anomalies. We identified a new family bringing to three the total families reported with this disorder. Our proband presented with anteriorly protruded ears and malformed ear pinnae in association with microphthalmia, congenital cataract, microcornea, and iris and optic disc colobomata. Additionally, he had high and broad forehead with asymmetry giving a recognizable facial gestalt. Further, short left mandibular ramus and bifid cingulum in the boy and short right mandibular ramus in his father were observed. Mutation analysis revealed a novel homozygous nonsense mutation c.487G>T in the second exon of the HMX1 that predicted to introduce a premature stop codon at position 163 (p.E163*). Parents showed the heterozygous state of the detected mutation. Investigations in a process as complex as craniofacial development suggest that there are still additional, as yet unidentified, genes that play in orchestrate to determine the final phenotype.

Keywords: HMX1 mutation; dysmorphic ear; enhancers; misplaced ear; oculoauricular syndrome; oro-dental abnormalities.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Cataract / genetics
  • Codon, Nonsense / genetics*
  • Coloboma / diagnosis
  • Consanguinity
  • Cornea / abnormalities
  • DNA Mutational Analysis
  • Ear / abnormalities*
  • Exons / genetics
  • Eye Abnormalities / diagnosis
  • Eye Abnormalities / genetics*
  • Female
  • Homeodomain Proteins / genetics*
  • Homozygote
  • Humans
  • Infant
  • Iris / abnormalities
  • Male
  • Microphthalmos / diagnosis
  • Optic Nerve / abnormalities
  • Pedigree
  • Phenotype
  • Transcription Factors / genetics*


  • Codon, Nonsense
  • Homeodomain Proteins
  • Transcription Factors

Supplementary concepts

  • Coloboma of optic nerve
  • Oculoauricular Syndrome