ALX1 gene


Gene (OMIM No.)
Function of gene/protein
  • Protein: Aristaless-like homeobox 1
  • Regulates other genes by binding to specific DNA regions (transcription factor)
  • Controls cell growth, division and movement during early development
  • Important for early development of the head and face, particularly the eyes, nose and mouth
Clinical phenotype
(OMIM phenotype no.)
  • Autosomal recessive
Ocular features
Systemic features
  • Craniofacial clefting (cleft palate, cleft lip, cranial cleft)
  • Dysmorphic facial features (prominent glabella, broad nasal bridge with hypoplasia of the ala nasi, low-set posteriorly rotated ears, smooth philtrum, mouth protrusion accompanied by teeth protrusion, brachycephaly)
  • Brain defects (delayed myelinisation, thin corpus callosum and asymmetric cerebellar vermis configuration)
  • Caudal appendage in the sacral region
  • Learning difficulties
Key investigations
  • B-scan USS to measure axial length to document microphthalmia
  • Electrophysiology
  • MRI brain and orbit
  • Systemic assessment with a paediatrician and other relevant specialists
Molecular diagnosisNext generation sequencing
  • Targeted gene panels (MAC)
  • Whole genome sequencing
  • Multidisciplinary approach
Therapies under research
  • None at present
Further information

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  1.  Uz E, Alanay Y, Aktas D, et al. Disruption of ALX1 Causes Extreme Microphthalmia and Severe Facial Clefting: Expanding the Spectrum of Autosomal-Recessive ALX-Related Frontonasal Dysplasia. Am J Hum Genet 2010; 86: 789–796
  2.  Ullah A, Kalsoom UE, Umair M, et al. Exome sequencing revealed a novel splice site variant in the ALX1 gene underlying frontonasal dysplasia. Clin Genet. 2017;91(3):494-498

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Updated on November 30, 2020

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