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Glaucoma, Congenital Primary D

OMIM ID:

autosomal recessive

Glaucoma, Congenital Primary D

Alternate Names

congenital glaucoma plus

Defective Genes

LTBP2

Clinical Characteristics

Ocular Features

Evidence of glaucoma can appear in early childhood but may appear much later.  However, typical signs such as enlarged corneas or frank buphthalmos, cloudiness of the corneas, tearing and photophobia are present only when the pressure is elevated due to pupillary block or when the lens migrates into the anterior chamber.  Most patients have additional signs such as ectopia lentis and spherophakia.

Systemic Features

Some patients have osteopenia, a high arched palate, and a marfanoid habitus.

Genetics

Inheritance

This form of congenital glaucoma has been described primarily in Middle Eastern and Asian as well as Roma/Gypsy families and is inherited in an autosomal recessive pattern.  The mutations occur in the LTBP2 gene (14q24) which is in close proximity to GLC3C, another putative gene with mutations causing congenital glaucoma. 

Mutations in other genes are also associated with primary congenital glaucoma such as in CYP1B1 causing type A (231300) and in GLC3B causing type B (600975).

THIS IS NOT A PRIMARY GLAUCOMA DISORDER.  Microspherophakia and ectopia lentis are not features of primary congenital glaucoma.  Elevated pressures in these patients are found only when there is a pupillary block or when the lens dislocates into the anterior chamber.  The enlarged cornea is clear and has no breaks in the Descemet membrane.  THIS CONDITION IS THEREFORE RECLASSIFIED AS “MEGALOCORNEA, ECTOPIA LENTIS, AND SPHEROPHAKIA”.     

Pedigree

Autosomal recessive

In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent.  Carriers with only one mutation, such as the parents, do not have clinical disease.  Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.

Image
Sample pedigree of autosomal recessive inheritance

In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.

Treatment & Management

The usual surgical and pharmacological treatments for glaucoma apply but vision preservation is a challenge.  The spherophakic or dislocated lenses may need to be removed.

Selected Resources

Publications

Displaying 1 - 2 of 2

LTBP2 and CYP1B1 mutations and associated ocular phenotypes in the Roma/Gypsy founder population

PubMedID: 21081970

Null Mutations in LTBP2 Cause Primary Congenital Glaucoma

PubMedID: 19361779