Table 2.

Disorders with Ectopia Lentis and/or Iris Anomalies to Consider in the Differential Diagnosis of ADAMTSL4-Related Eye Disorders

DisorderGene(s)MOIDistinguishing Clinical Features of Disorder
Ectopia lentis (OMIM 129600)FBN1 1ADMay incl the systemic features of Marfan syndrome
Homocystinuria caused by cystathionine beta-synthase deficiency CBS AR
  • Tall, thin stature
  • High-arched feet
  • Chest anomalies
  • Intellectual disability
  • Seizures
  • Arterial atheroma formation
Isolated sulfite oxidase deficiency SUOX AR
  • Seizures
  • Ataxia
  • Dystonia
  • Choreoathetotic movements
Weill-Marchesani syndrome (WMS) ADAMTS10
FBN1
LTPBP2 		AD 2
AR 2
  • Proportionate short stature
  • Brachydactyly
  • Joint stiffness
WMS-like syndrome (OMIM 613195) ADAMTS17 ARBrachydactyly
MSPKA (OMIM 251750) LTBP2 AR
  • Megalocornea
  • Glaucoma
  • Microspherophakia
  • Axial myopia
  • Marfanoid features
Aniridia PAX6 AD
  • Iris hypoplasia
  • Foveal dysplasia
  • Optic nerve hypoplasia
  • Nystagmus
Axenfeld-Rieger syndrome type 1 (OMIM 180500) PITX2 AD
  • Embryotoxon posterior
  • Iridocorneal adhesions
  • Iris anomalies
Iridocorneal endothelial syndrome 3NA 4NA 4
  • Corneal edema
  • Corneal endothelial irregularities
  • Polycoria
  • Iris nevus
Iris coloboma>30AD
AR
XL		Variable 5
Anterior segment dysgeneses (OMIM PS107250) CPAMD8
CYP1B1
FOXC1
FOXE3
PAX6
PITX2
PITX3
PXDN 		AD
AR
  • Microphthalmia
  • Embryotoxon posterior
  • Corneal opacities
  • Sclerocornea
  • Iris hypoplasia
  • Iridocorneal adhesions
  • Glaucoma
Posterior polymorphous corneal dystrophy (OMIM PS122000) COL8A2
OVOL2
ZEB1 		AD
  • Posterior corneal opacities
  • Iridocorneal adhesions
  • Glaucoma

AD = autosomal dominant; AR = autosomal recessive; MOI = mode of inheritance; MSPKA = microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma; XL= X-linked

1.

Ectopia lentis most frequently occurs as an autosomal dominant disorder in association with pathogenic variants in FBN1 (OMIM 134797) that may (OMIM 154700) or may not (OMIM 129600) be accompanied by the systemic features of Marfan syndrome.

2.

Pathogenic variants in ADAMTS10 are known to cause autosomal recessive WMS. Biallelic pathogenic variants in LTPBP2 have been reported in one family with autosomal recessive inheritance [Haji-Seyed-Javadi et al 2012]. A heterozygous pathogenic variant in FBN1 has been identified in one family with autosomal dominant WMS [Faivre et al 2003].

3.
4.

This is an acquired disorder and rarely seen in children.

5.

There are many genes associated with iris coloboma, and accompanying features can be quite complex.

From: ADAMTSL4-Related Eye Disorders

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