ADAMTS18 gene

Overview

Gene (OMIM No.)
Function of gene/protein
  • Protein: A disintegrin and metalloproteinase with thrombospondin motifs 18
  • Exact function in ocular development is still not known
  • Highly expressed in brain
Clinical phenotype
(OMIM phenotype no.)
  • Microcornea, myopic chorioretinal atrophy and telecanthus; MMCAT (#615458)
Inheritance
  • Autosomal recessive
Ocular features
  • Telecanthus
  • Anterior segment dysgenesis (microcornea, ectopic pupils, ectopia lentis and childhood cataract)
  • Microcornea is a consistent feature
  • Range of refractive error ranging from high myopia (<-6.00D) to hypermetropia (up to +6.25D)
  • Early onset severe retinal degeneration (cone-rod phenotype)
  • Peripheral retinal and macular pigmentation
  • Rhegmatogenous retinal detachment
  • Chorioretinal atrophy
Systemic features
  • Craniofacial anomalies (Posteriorly rotated ears, broad nasal tip)
Key investigations
  • Scheimpflug imaging (Pentacam) and anterior segment OCT to assess corneal diameter, shape, thickness and anterior segment structures
  • B-scan USS to measure axial length to document microphthalmia if present
  • Measurement of intraocular pressure
  • Gonioscopy
  • Full field ERG: Mild depression and delay in rod and cone responses, cone-rod dystrophy
  • Pattern ERG: Reduction in amplitude if macular involvement
  • MRI brain and orbit
  • Systemic assessment by a paediatrician for any extraocular involvement
Molecular diagnosisNext generation sequencing
  • Targeted gene panels (retinal/ASD)
  • Whole exome sequencing
  • Whole genome sequencing
ManagementOcularSystemic
  • Multidisciplinary approach
Therapies under research
  • None at present
Further information

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Additional information

The ADAMTS18 phenotype has overlapping features with Knobloch syndrome due to pathogenic mutations in the COL18A1 gene. It is characterised by anterior segment dysgenesis (cryptless iridies and ectopia lentis), high myopia, vitreoretinal degeneration (leading to an increased risk of retinal detachment) and occipital skull malformation.[1,2] The latter feature has not been associated with mutations in ADAMTS18.[3]

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References

  1.  Khan AO, Aldahmesh MA, Mohamed JY, Al-Mesfer S, Alkuraya FS. The distinct ophthalmic phenotype of Knobloch syndrome in children. Br J Ophthalmol. 2012;96(6):890-895
  2.  Seaver LH, Joffe L, Spark RP, Smith BL, Hoyme HE. Congenital scalp defects and vitreoretinal degeneration: redefining the Knobloch syndrome. Am J Med Genet. 1993;46(2):203-208
  3.  Chandra A, Arno G, Williamson K, et al. Expansion of ocular phenotypic features associated with mutations in ADAMTS18 [published correction appears in JAMA Ophthalmol. 2014 Sep;132(9):1153]. JAMA Ophthalmol. 2014;132(8):996-1001
  4.  Khan AO. Microcornea with myopic chorioretinal atrophy, telecanthus and posteriorly-rotated ears: a distinct clinical syndrome [published correction appears in Ophthalmic Genet. 2013 Sep;34(3):182]. Ophthalmic Genet. 2012;33(4):196-199
  5.  Aldahmesh MA, Alshammari MJ, Khan AO, Mohamed JY, Alhabib FA, Alkuraya FS. The syndrome of microcornea, myopic chorioretinal atrophy, and telecanthus (MMCAT) is caused by mutations in ADAMTS18. Hum Mutat. 2013;34(9):1195-1199

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Updated on November 30, 2020
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