Glaucoma Syndromes: Insights into Glaucoma Genetics and Pathogenesis from Monogenic Syndromic Disorders

Genes (Basel). 2021 Sep 11;12(9):1403. doi: 10.3390/genes12091403.

Abstract

Monogenic syndromic disorders frequently feature ocular manifestations, one of which is glaucoma. In many cases, glaucoma in children may go undetected, especially in those that have other severe systemic conditions that affect other parts of the eye and the body. Similarly, glaucoma may be the first presenting sign of a systemic syndrome. Awareness of syndromes associated with glaucoma is thus critical both for medical geneticists and ophthalmologists. In this review, we highlight six categories of disorders that feature glaucoma and other ocular or systemic manifestations: anterior segment dysgenesis syndromes, aniridia, metabolic disorders, collagen/vascular disorders, immunogenetic disorders, and nanophthalmos. The genetics, ocular and systemic features, and current and future treatment strategies are discussed. Findings from rare diseases also uncover important genes and pathways that may be involved in more common forms of glaucoma, and potential novel therapeutic strategies to target these pathways.

Keywords: Aicardi–Goutieres syndrome; Axenfeld–Rieger syndrome; Peter’s anomaly; Singleton–Merten syndrome; Stickler syndrome; aniridia; anterior segment dysgenesis; juvenile open-angle glaucoma; mucopolysaccharidosis; nanophthalmos; osteogenesis imperfecta; pediatric glaucoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aniridia / genetics
  • Aniridia / pathology
  • Collagen Diseases / complications
  • Collagen Diseases / genetics
  • Collagen Diseases / pathology
  • Eye Abnormalities / genetics
  • Eye Abnormalities / pathology
  • Eye Diseases, Hereditary / genetics*
  • Eye Diseases, Hereditary / pathology
  • Glaucoma / etiology*
  • Glaucoma / genetics*
  • Glaucoma / pathology
  • Glaucoma, Angle-Closure / complications
  • Glaucoma, Angle-Closure / genetics
  • Glaucoma, Angle-Closure / pathology
  • Humans
  • Hyperopia / complications
  • Hyperopia / genetics
  • Hyperopia / pathology
  • Immune System Diseases / complications
  • Immune System Diseases / genetics
  • Immune System Diseases / pathology
  • Metabolic Diseases / complications
  • Metabolic Diseases / genetics
  • Metabolic Diseases / pathology
  • Microphthalmos / complications
  • Microphthalmos / genetics
  • Microphthalmos / pathology
  • Syndrome
  • Vascular Diseases / complications
  • Vascular Diseases / genetics
  • Vascular Diseases / pathology

Supplementary concepts

  • Anterior segment mesenchymal dysgenesis
  • Nanophthalmos 1