GDF6 gene


Gene (OMIM No.)
Function of gene/protein
  • Protein: growth differentiation factor 6
  • Part of the TGFβ superfamily
  • Involved in regulating growth and maturation of bone, cartilage and the retina
  • Regulates apoptosis during photoreceptor development
Clinical phenotype
(OMIM phenotype no.)
  • Klippel-Feil syndrome 1, autosomal dominant (#118100)
  • LCA/EOSRD: Leber congenital amaurosis 17 (#615360)
  • Microphthalmia with coloboma 6, digenic (#613703)
  • Microphthalmia, isolated 4 (#613094)
  • Multiple synostoses syndrome 4 (#617898)
  • Autosomal dominant in most cases
  • Autosomal recessive in a patient diagnosed with LCA
Ocular features
Systemic features
  • Klippel-Feil syndrome (verterbral segmentation defects leading to a fused appearance)
  • Other skeletal anomalies (malformed ossicles, post-axial polydactyly, hemivertebrae, rib malformations)
  • Craniofacial (hemifacial hypoplasia, cleft lip and palate)
  • Genital anomalies (phimosis and single testis)
Key investigations
  • B-scan USS to measure axial length to document microphthalmia
  • Electrophysiology
  • MRI brain and orbit
  • Spine X-ray
  • 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.  Asai-Coakwell M, French CR, Ye M, et al. Incomplete penetrance and phenotypic variability characterize Gdf6-attributable oculo-skeletal phenotypes. Hum Mol Genet. 2009;18(6):1110‐1121
  2.  Asai-Coakwell M, March L, Dai XH, et al. Contribution of growth differentiation factor 6-dependent cell survival to early-onset retinal dystrophies. Hum Mol Genet. 2013;22(7):1432‐1442
  3.  Tassabehji M, Fang ZM, Hilton EN, et al. Mutations in GDF6 are associated with vertebral segmentation defects in Klippel-Feil syndrome. Hum Mutat. 2008;29(8):1017‐1027
  4.  Wang J, Yu T, Wang Z, et al. A New Subtype of Multiple Synostoses Syndrome Is Caused by a Mutation in GDF6 That Decreases Its Sensitivity to Noggin and Enhances Its Potency as a BMP Signal. J Bone Miner Res. 2016;31(4):882‐889
  5.  Zhang L, Lim SL, Du H, et al. High temperature requirement factor A1 (HTRA1) gene regulates angiogenesis through transforming growth factor-β family member growth differentiation factor 6. J Biol Chem. 2012;287(2):1520‐1526
  6.  Gonzalez-Rodriguez J, Pelcastre EL, Tovilla-Canales JL, et al. Mutational screening of CHX10, GDF6, OTX2, RAX and SOX2 genes in 50 unrelated microphthalmia-anophthalmia-coloboma (MAC) spectrum cases. Br J Ophthalmol. 2010;94(8):1100‐1104
  7.  den Hollander AI, Biyanwila J, Kovach P, et al. Genetic defects of GDF6 in the zebrafish out of sight mutant and in human eye developmental anomalies. BMC Genet. 2010;11:102

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Updated on November 30, 2020
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