Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Sep 4:28:257-268.
eCollection 2022.

The phenotypic spectrum of ADAMTSL4- associated ectopia lentis: Additional cases, complications, and review of literature

Lachlan S W Knight  1 , Sean Mullany  1 , Deepa A Taranath  1 , Jonathan B Ruddle  2   3   4 , Christopher P Barnett  5 , Suzanne C E H Sallevelt  5 , Ella C Berry  1 , Henry N Marshall  1 , Georgina L Hollitt  1 , Emmanuelle Souzeau  1 , Jamie E Craig  1 , Owen M Siggs  1   6
Affiliations
Review

The phenotypic spectrum of ADAMTSL4- associated ectopia lentis: Additional cases, complications, and review of literature

Lachlan S W Knight et al. Mol Vis. .

Abstract

Purpose: ADAMTSL4-associated ectopia lentis is a rare autosomal recessive condition that is primarily associated with crystalline lens displacement. However, the prevalence of other ocular and systemic manifestations of this condition is poorly understood. In this study, we summarize the ocular and systemic phenotypic spectrum of this condition.

Methods: A cross-sectional case study series of four individuals with biallelic pathogenic or likely pathogenic ADAMTSL4 variants was performed alongside a literature review of individuals with ADAMTSL4-associated ectopia lentis on September 29, 2021. Ocular and systemic findings, complications, and genetic findings of all four individuals were collected and summarized.

Results: The phenotypic spectrum across 91 individuals sourced from literature and four individuals from this case study series was highly variable. The main ocular phenotypes included ectopia lentis (95/95, 100%), ectopia lentis et pupillae (18/95, 19%), iris transillumination (13/95, 14%), iridodonesis (12/95, 13%), persistent pupillary membrane (12/95, 13%), and early-onset cataract or lens opacities (12/95, 13%). Anterior segment features other than ectopia lentis appeared to be exclusively associated with biallelic loss of function variants (p<0.001). Pupillary block glaucoma had a prevalence of 1%. Post-lensectomy complications included retinal detachment (6/41, 15%), elevated intraocular pressure (4/41, 10%), and aphakic glaucoma (1/41, 2%). Most individuals were not reported to have had systemic features (69/95, 73%).

Conclusions: The clinical phenotype of ADAMTSL4-associated ectopia lentis was summarized and expanded. Clinicians should be aware of the varied ocular phenotype and the risks of retinal detachment, ocular hypertension, and glaucoma in the diagnosis and management of this condition.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Pedigrees of families A, B, and C. The filled symbols denote the affected individuals. The arrow denotes the proband.
Figure 2
Figure 2
Clinical photography. The slit lamp imaging shows A: iris transillumination defects, B: a persistent pupillary membrane, and C: posterior lentiglobus or spherophakia on the slit illumination observed in Individual A-II-2. D: Ectopia lentis seen in Individual A-II-1 OD.
Figure 3
Figure 3
Prevalence of ocular and systemic features stratified by the predicted loss of the function allele count. Other anterior segment features included: ectopia lentis et pupillae, iris transillumination defect, iridodonesis, persistent pupillary membrane, poor pupillary dilatation, spherophakia, corectopia, iris coloboma, lens coloboma, posterior synechiae, and iris processes. The posterior segment features included retinal detachment, axial length ≥ 27.0 mm, and posterior staphyloma. The anterior segment features other than ectopia lentis appeared to have been exclusively associated with biallelic loss of function variants (p < 0.001). LoF: loss of function variant; non-LoF: non-loss of function variant. The bold values indicate statistical significance. aChi-square test with continuity correction, bFisher exact test.
See this image and copyright information in PMC

References

    1. Rødahl E, Mellgren AEC, Boonstra NE, Knappskog PM. ADAMTSL4-Related Eye Disorders. GeneReviews. 2012.
    1. Cruysberg JR, Pinckers A. Ectopia lentis et pupillae syndrome in three generations. Br J Ophthalmol. 1995;79:135–8. - PMC - PubMed
    1. Neuhann TM, Stegerer A, Riess A, Blair E, Martin T, Wieser S, Kläs R, Bouman A, Kuechler A, Rittinger O. ADAMTSL4-associated isolated ectopia lentis: Further patients, novel mutations and a detailed phenotype description. Am J Med Genet A. 2015;167A:2376–81. - PubMed
    1. Sharifi Y, Tjon-Fo-Sang MJ, Cruysberg JRM, Johannes RM, Matt-Kievit AJ. Ectopia lentis et pupillae in four generations caused by novel mutations in the ADAMTSL4 gene. Br J Ophthalmol. 2013;97:583–7. - PubMed
    1. Overwater E, Floor K, van Beek D, de Boer K, van Dijk T, Hilhorst-Hofstee Y, Hoogeboom AJM, van Kaam KJ, van de Kamp JM, Kempers M, Krapels IPC, Kroes HY, Loeys B, Salemink S, Stumpel CTRM, Verhoeven VJM, Wijnands-van den Berg E, Cobben JM, van Tintelen JP, Weiss MM, Houweling AC, Maugeri A. NGS panel analysis in 24 ectopia lentis patients; a clinically relevant test with a high diagnostic yield. Eur J Med Genet. 2017;60:465–73. - PubMed

Publication types