Glaucoma Genetics

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There are many inheritable forms of glaucoma, both primary and secondary. While inheritance patterns and genetics are not perfectly mapped out for glaucoma, there are some basic observations that can help us screen for glaucoma among family members:

  • Many cases have an autosomal dominant inheritance pattern.
  • There is incomplete penetrance.
  • Environmental factors play a large role in the expression of glaucoma.
  • Family history is a risk factor for the development of primary open angle glaucoma (POAG).
  • 10% of glaucoma patients have siblings with glaucoma.

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Glaucoma Genes

There are many genes that have been identified in various forms of glaucoma. While genetic testing for glaucoma is not commonplace, many of these genetic markers do provide some insight into the different mechanisms and components that affect the phenotype we call glaucoma.

While this list is not comprehensive, it highlights a few of the key genotypes that we know contribute to the formation of glaucoma.

Open Angle Glaucomas (GLC1)

Many of the open angle glaucoma genes carry the GLC1 designation, with subtypes lettered following GLC1: GLC1A, GLC1B, etc. This nomenclature may help make it a bit easier to remember what type of glaucoma a particular gene encodes for. As of the American Academy of Ophthalmology’s 2016-2017 Basic and Clinical Science Course publication, there are genes listed for GLC1A-GLC1K.

Primary Open Angle Glaucoma


The GLC1A gene, which is also called the Trabecular meshwork Inducible Glucocorticoid Response/MYOCillin gene (TIGR/MYOC), encodes the TIGR/myocillin protein, which is found within the trabecular meshwork. It was the first gene identified for POAG, and is located on chromosome 1 (“first gene discovered, first subtype [GLC1A], found on chromosome 1″).

3% of POAG patients carry the GLC1A gene, and it is transmitted in an autosomal dominant fashion.


The GLC1C gene is found on chromosome 3 (“C is the 3rd letter of the English alphabet, chromosome 3”). It is associated with a late-onset primary open angle glaucoma that causes high pressure and is only moderately responsive to medications.


The GLC1G gene is found on chromosome 5. It is also known as the WDR36 gene.

Normal Tension Glaucoma

There are 2 genes that have been described in normal-tension (low pressure) glaucoma: GLC1B and GLC1E. A helpful mnemonic for remembering these genes is “BE normal,” which refers to the subtypes of the two genes, B and E.


The GLC1B gene is located on chromosome 2 (“B is the second letter of the English alphabet, chromosome 2”).


The GLC1E gene is located on chromosome 10. It encodes for the optineurin protein, which is why the other designation for this gene is OPTN (“op-ten-neurin” is a way to help remember the chromosome for this gene).

Secondary Open Angle Glaucomas

Pseudoexfoliation glaucoma (LOXL1)

Pseudoexfoliation syndrome (PXE) is a systemic condition in which there is deposition of a fibrillar material throughout the body, especially in the anterior segment, and is the most common secondary open angle glaucoma. It is associated with the LOXL1 gene, located on chromosome 15.

Pigment Dispersion Syndrome (GPDS1)

Pigment dispersion syndrome (PDS) is another fairly common cause of secondary open angle glaucoma most typically found in young myopic males. The GPDS1 gene, located on chromosome 7, is associated with PDS.

Angle Closure Glaucoma (GLC2)

There is a gene associated with primary angle closure glaucoma, termed GLC2. It is found on chromosome 11, and there are several different mutations, resulting in both autosomal dominant and autosomal recessive forms.

Congenital and Pediatric Glaucomas

Congenital Glaucomas (GLC3)

There are many causes of congenital glaucoma, with currently 4 genes identified. These genes all start with GLC3 and are lettered A-D (GLC3A, etc.). Unlike almost all of the rest of the glaucoma genes, which are inherited in an autosomal dominant pattern, congenital glaucoma genes are inherited in an autosomal recessive pattern.

One way to help remember that congenital glaucoma is GLC3 is by remembering that congenital glaucoma presents in a triad of blepharospasm, epiphora, and photophobia.


GLC3A has been identified as encoding the CYP1B1 gene and is found on chromosome 2.


GLC3B is found on chromosome 1.


GLC3C and GLC3D are found on chromosome 14.

Pediatric Glaucomas

There are several syndromes that are associated with the presentation of glaucoma in childhood. While many of these conditions are associated with anterior segment dysgenesis, this is not the only pathogenesis for glaucoma in childhood. A few of these conditions are listed here.

Nanophthalmos (NNO1, VMD2, MFRP)

There are several genes associated with the formation of nanophthalmos, all of which are found on chromosome 11. NNO1 and VMD2 are inherited in an autosomal dominant pattern, and MFRP is inherited in an autosomal recessive pattern.

I need to do some more digging, but I believe that the VMD2 gene on chromosome 11 is the same gene associated with Best vitelliform dystrophy of the retina. If so, it’s an interesting connection.

Axenfeld-Rieger Syndrome (RIEG1/PITX2, RIEG2, IRID1/FOXC1)

Axenfeld-Rieger syndrome is a spectrum of anterior segment dysgenesis that can be caused by many different genes, all inherited in an autosomal dominant pattern. RIEG1, or PITX2, is found on chromosome 4, RIEG2 is found on chromosome 13, and IRID1, or FOXC1, is found on chromosome 6.

Nail-Patella Syndrome (NPS/LMXB1)

Nail-patella syndrome (NPS) is a rare condition that primarily affects the nails, knees, elbows, and pelvis. However, it has been implicated in childhood glaucoma, and thus has been on the list of conditions associated with glaucoma. The gene associated with nail-patella syndrome is LMX1B, and is found on chromosome 9.

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Essentials To Know

Here are some key points to remember:

  • Almost all of the glaucoma genes, with the noted exception of congenital glaucomas, are inherited in an autosomal dominant pattern.
  • Congenital glaucomas (GLC3) and the MFRP variant of nanophthalmos are inherited in an autosomal recessive pattern.
  • Normal tension glaucoma genes are GLC1B and GLC1E (“BE normal”).
  • The first gene identified in open angle glaucoma, GLC1A, is located on chromosome 1 and encodes the TIGR/myocillin protein (“TIGR is number 1”).

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Summary Table

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References and Additional Reading

  1. American Academy of Ophthalmology. Basic and Clinical Science Course, Section 10: Glaucoma. 2016-2017 ed. San Francisco: American Academy of Ophthalmology, 2016:10-11.
  2. Nail-Patella Syndrome. Genetics Home Reference, National Library of Medicine, National Institutes of Health. Website.
  3. Allingham RR, Liu Y, Rhee DJ. The genetics of primary open-angle glaucoma: a review. Exp Eye Res. 2009;88(4):837-844.
  4. Stone EM, Fingert JH, Alward WL, et al. Identification of a gene that causes primary open angle glaucoma. Science. 1997;275(5300):668-670.
  5. Wolfs RC, Klaver CC, Ramrattan RS, van Duijn CM, Hofman A, de Jong PT. Genetic risk of primary open-angle glaucoma: population-based familial aggregation study. Arch Ophthalmol. 1998;116(112):1640-1645.

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Do you have any other tips on how to remember glaucoma genetics? Leave a comment or e-mail us at!


BCSC Reading: Week 3

Week 3 Reading Assignment and Statistics

Reading Plan Book/Chapters Topics Pages Total Pages Pages/Day
AAO* Fundamentals 14-End RPE, ocular pharmacology 271-389 118 17
Ophthalmology Review** Fundamentals 4-6 Embryology, genetics 111-232 122 18

*The AAO reading schedule is based off the 2016-2017 BCSC series, available starting June 15, 2016.

**My reading schedule is based off the 2012-2013 BCSC series, as I do not own the new editions.


Since there are multiple ways to read through the BCSC, I decided to format the reading schedule based on weeks, rather than post multiple reading events.  This also allows me to reuse these events every year, instead of creating this again next year.

The two featured reading schedules are adapted from Dr. Brian T. Chan-Kai’s article on the American Academy of Ophthalmology’s website, and the reading schedule my colleagues and I used in residency.  While my reading schedule may typically seem a bit lighter, keep in mind that Dr. Chan-Kai’s schedule takes less time (31 weeks vs. 34 weeks), and goes through 12 of the 13 texts (mine covers 11 of 13).

Additionally, Dr. Chan-Kai starts the reading two weeks into the new residency year (presumably to allow for orientation and such).  I am going to start the reading schedule on this site on July 1 for simplicity, and also to allow for a few weeks of review at the end before the OKAP.  Obviously, these are all guidelines, and you can adapt the schedule however you see fit.

For someone wanting to read through the BCSC in a year to study for the ABO Written Qualifying Exam, this reading schedule should be modified, in that the written board exam doesn’t test on Section 1:  Update on General Medicine or Section 2:  Fundamentals and Principles of Ophthalmology.

Week 3 Overview

This week finishes up Section 2:  Fundamentals and Principles of Ophthalmology.  Dr. Chan-Kai’s plan completely finishes the book with this week’s reading.  The reading schedule I followed reserved some of the physiology chapters for their respective major sections.

The AAO Plan:

This week’s reading assignment covers the RPE and ocular pharmacology, and the page count includes the study questions in the back of the book.  I highly recommend that you quiz yourself with those questions at the end of each book – though they are typically pretty basic questions, they (like other practice questions) help you get a better sense of what information you really need to know and understand.

Ophthalmology Review Plan:

In my opinion, this week was a fairly light reading assignment.  Understanding ocular development in embryology is very important, but like I mentioned in week 2, the genetics of each individual disease will be revisited in subsequent books.  For this reason, if you wanted to move this reading assignment to a different week where you’re far busier or on vacation or something, this would be a good reading block to move.

Week 3 Tips and Helpful Resources

For tips on reading these sections, please check out the following pages (I will be working on developing more content for this section):

Review, Pediatric Ophthalmology: Phakomatoses (An Overview)

Phakomatoses are a multidisciplinary category of systemic diseases that is often tested for a multitude of reasons.  Although the incidence of these conditions is fairly low (though chances are you will see at least 1 case of many of these conditions), there are many ocular findings that need to be considered.

I’ve been debating how to organize this information in a useful manner for review for quite some time.  The subject material is pretty massive, and each condition could easily take several articles (and probably eventually will).  But I wanted to make sure there was a useful review out there on this subject before the written board exam, in case the test covers one of these conditions.

For this article, I’m going to organize the phakomatoses in a series of different tables/lists that can be used as quick references.  If you all have any suggestions or requests for putting this information together, I’d be happy to add to this resource! Continue reading “Review, Pediatric Ophthalmology: Phakomatoses (An Overview)”

OKAP Review, Pediatric Ophthalmology: Aniridia

As you can probably tell, I’m starting to skip around a little bit while I put together these OKAP review articles.  I have a fairly large list of topics to cover, but hopefully these will all be helpful pieces of information.  I decided to skip to aniridia, because it is one of those conditions that seems to be very popular in practice questions.


Image from AAPOS.

As the figure states, aniridia refers to the absence of the iris.  In most cases, there can be a residual stump or only partial aniridia; complete absence of the iris is actually less common.

Inheritance and Genetics

  • PAX6:  PAX6 is a transcription factor for eye development.  It is inherited in an autosomal dominant pattern, and its disruption is the most common cause of aniridia.
  • PAX6 gene mutations are an example of haploinsufficiency – for some proteins, both genes need to be functioning normally to produce a normal result.
  • In rare cases, aniridia can also be inherited in a sporadic or autosomal recessive fashion.  De novo mutations are associated with Wilms tumor (see below).

Continue reading “OKAP Review, Pediatric Ophthalmology: Aniridia”

Jeopardy Review: Fundamentals of Ophthalmology (Round 1)

For those of you who might enjoy a Jeopardy!-style review format, I created one for some of the fundamental topics.  I admit, some of the questions may not be easily answered until you’ve studied the whole of ophthalmology, but hopefully this will be a useful review.

I created this Jeopardy!-style review at, which lets you create Jeopardy! boards for free!  The full-frame web version of this review can be found here.