OTX2 gene


Gene (OMIM No.)
Function of gene/protein
  • Vital for correct brain and eye development
  • Regulates other genes by binding to specific DNA regions (transcription factor)
Clinical phenotype
(OMIM phenotype no.)
  • Microphthalmia, syndromic 5 (#610125)
  • Retinal dystrophy, early onset, with or without pituitary dysfunction (#610125)
  • Pituitary hormone deficiency, combined, 6 (#613986)
  • De novo sporadic
  • Autosomal dominant
Ocular features
Systemic featuresMicrophthalmia, syndromic 5 and retinal dystrophy, early onset, with or without pituitary dysfunction:
  • Pituitary abnormalities (hypoplasia, ectopic posterior pituitary)
  • Growth retardation
  • Psychomotor delay
  • Hypotonia
  • Seizures, cleft palate, dysgnathia/agnathia and corpus callosum agenesis in some cases
Pituitary hormone deficiency, combined, 6:
  • Growth hormone deficiency
  • Combined with impaired production of 1 or more of the other 5 anterior pituitary hormones
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.  Boncinelli E, Gulisano M, Broccoli V. Emx and Otx homeobox genes in the developing mouse brain. J Neurobiol. 1993;24(10):1356‐1366
  2.  Chassaing N, Sorrentino S, Davis EE, et al. OTX2 mutations contribute to the otocephaly-dysgnathia complex. J Med Genet. 2012;49(6):373‐379
  3.  Dateki S, Fukami M, Sato N, Muroya K, Adachi M, Ogata T. OTX2 mutation in a patient with anophthalmia, short stature, and partial growth hormone deficiency: functional studies using the IRBP, HESX1, and POU1F1 promoters. J Clin Endocrinol Metab. 2008;93(10):3697‐3702
  4.  Diaczok D, Romero C, Zunich J, Marshall I, Radovick S. A novel dominant negative mutation of OTX2 associated with combined pituitary hormone deficiency. J Clin Endocrinol Metab. 2008;93(11):4351‐4359
  5.  Florell SR, Townsend JJ, Klatt EC, et al. Aprosencephaly and cerebellar dysgenesis in sibs. Am J Med Genet. 1996;63(4):542‐548
  6.  Ragge NK, Brown AG, Poloschek CM, et al. Heterozygous mutations of OTX2 cause severe ocular malformations [published correction appears in Am J Hum Genet. 2005 Aug;77(2):334]. Am J Hum Genet. 2005;76(6):1008‐1022
  7.  Tajima T, Ohtake A, Hoshino M, et al. OTX2 loss of function mutation causes anophthalmia and combined pituitary hormone deficiency with a small anterior and ectopic posterior pituitary. J Clin Endocrinol Metab. 2009;94(1):314‐319
  8.  Vincent A, Forster N, Maynes JT, et al. OTX2 mutations cause autosomal dominant pattern dystrophy of the retinal pigment epithelium. J Med Genet. 2014;51(12):797‐805

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Updated on November 30, 2020
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