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Congenital megalocornea with zonular weakness and childhood lens-related secondary glaucoma - a distinct phenotype caused by recessive LTBP2 mutations.

Khan AO, Aldahmesh MA, Alkuraya FS - Mol. Vis. (2011)

Bottom Line: One member from each family developed spontaneous complete crystalline lens dislocation into the anterior chamber with associated acute glaucoma during early childhood.LTBP2 sequencing in the third family revealed a third novel homozygous mutation (p.C1438Y [c.4313G>A]).Complete dislocation of the crystalline lens into the anterior chamber during early childhood can occur in young children with this unique phenotype.

View Article: PubMed Central - PubMed

Affiliation: Division of Pediatric Ophthalmology, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia. arif.khan@mssm.edu

ABSTRACT

Purpose: To clinically and genetically characterize a distinct phenotype of congenital megalocornea (horizontal corneal diameter ≥13 mm) with secondary glaucoma from spherophakia and/or ectopia lentis during childhood in affected Saudi families.

Methods: Clinical exam, homozygosity scan, and candidate gene analysis.

Results: From 2005 to 2010, eight affected individuals from three consanguineous families were identified. In addition to congenital megalocornea, affected children presented with secondary glaucoma from spherophakia and/or ectopia lentis. One member from each family developed spontaneous complete crystalline lens dislocation into the anterior chamber with associated acute glaucoma during early childhood. Older individuals had phenotypes that would have suggested prior uncontrolled primary congenital/infantile glaucoma had past ophthalmic and/or family histories not been available. Homozygosity mapping performed for the first two families suggested the candidate gene latent transforming growth factor-beta-binding protein 2 (LTBP2), which when sequenced revealed a novel homozgyous mutation that segregated with the phenotype in each family (p.S338PfsX4 [c.1012delT], p.Q1619X[(c.4855C>T]). LTBP2 sequencing in the third family revealed a third novel homozygous mutation (p.C1438Y [c.4313G>A]).

Conclusions: Congenital megalocornea with childhood secondary glaucoma from spherophakia and/or ectopia lentis is a distinct condition caused by recessive LTBP2 mutations that needs to be distinguished from buphthalmos secondary to primary congenital/infantile glaucoma because typical initial surgical treatment is lens removal in the former and angle surgery in the latter. Complete dislocation of the crystalline lens into the anterior chamber during early childhood can occur in young children with this unique phenotype.

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Related in: MedlinePlus

Family 1: cousin of the proband. A: At one year of age, large corneas are evident (14 mm horizontal diameters) but without corneal haze/scarring or Descemet breaks. B: After primary Ahmed valve implantation in both eyes, the crystalline lens dislocated into the posterior chamber and retinal tears developed bilaterally. The right eye is shown.
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f2: Family 1: cousin of the proband. A: At one year of age, large corneas are evident (14 mm horizontal diameters) but without corneal haze/scarring or Descemet breaks. B: After primary Ahmed valve implantation in both eyes, the crystalline lens dislocated into the posterior chamber and retinal tears developed bilaterally. The right eye is shown.

Mentions: The proband's cousin with a history of congenital glaucoma was recalled and examined. He was a 14-year-old boy with pre-phthisical eyes and a history of multiple intraocular surgeries. His parents were cousins. He was tall and thin with a relatively high arched palate, but had no other features to suggest Marfan syndrome (no arachnodactyly, no chest depression, no relatively increased arm span, no electrocardiographic abnormalities). A review of the records revealed that at one year of age he underwent his first ocular surgery, bilateral primary Ahmed valve implantation for presumed primary congenital/infantile glaucoma. However, although megalocornea (horizontal corneal diameters of 14 mm) was documented preoperatively, other expected phenotypic features for buphthalmos from primary congenital/infantile glaucoma were not (e.g., corneal haze/scarring, Descemet breaks, optic disc cupping; Figure 2A). Despite uncomplicated surgery, post-operatively the child developed complete posterior dislocation of the crystalline lenses into the posterior vitreous cavities with giant retinal tears bilaterally (Figure 2B).


Congenital megalocornea with zonular weakness and childhood lens-related secondary glaucoma - a distinct phenotype caused by recessive LTBP2 mutations.

Khan AO, Aldahmesh MA, Alkuraya FS - Mol. Vis. (2011)

Family 1: cousin of the proband. A: At one year of age, large corneas are evident (14 mm horizontal diameters) but without corneal haze/scarring or Descemet breaks. B: After primary Ahmed valve implantation in both eyes, the crystalline lens dislocated into the posterior chamber and retinal tears developed bilaterally. The right eye is shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3198484&req=5

f2: Family 1: cousin of the proband. A: At one year of age, large corneas are evident (14 mm horizontal diameters) but without corneal haze/scarring or Descemet breaks. B: After primary Ahmed valve implantation in both eyes, the crystalline lens dislocated into the posterior chamber and retinal tears developed bilaterally. The right eye is shown.
Mentions: The proband's cousin with a history of congenital glaucoma was recalled and examined. He was a 14-year-old boy with pre-phthisical eyes and a history of multiple intraocular surgeries. His parents were cousins. He was tall and thin with a relatively high arched palate, but had no other features to suggest Marfan syndrome (no arachnodactyly, no chest depression, no relatively increased arm span, no electrocardiographic abnormalities). A review of the records revealed that at one year of age he underwent his first ocular surgery, bilateral primary Ahmed valve implantation for presumed primary congenital/infantile glaucoma. However, although megalocornea (horizontal corneal diameters of 14 mm) was documented preoperatively, other expected phenotypic features for buphthalmos from primary congenital/infantile glaucoma were not (e.g., corneal haze/scarring, Descemet breaks, optic disc cupping; Figure 2A). Despite uncomplicated surgery, post-operatively the child developed complete posterior dislocation of the crystalline lenses into the posterior vitreous cavities with giant retinal tears bilaterally (Figure 2B).

Bottom Line: One member from each family developed spontaneous complete crystalline lens dislocation into the anterior chamber with associated acute glaucoma during early childhood.LTBP2 sequencing in the third family revealed a third novel homozygous mutation (p.C1438Y [c.4313G>A]).Complete dislocation of the crystalline lens into the anterior chamber during early childhood can occur in young children with this unique phenotype.

View Article: PubMed Central - PubMed

Affiliation: Division of Pediatric Ophthalmology, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia. arif.khan@mssm.edu

ABSTRACT

Purpose: To clinically and genetically characterize a distinct phenotype of congenital megalocornea (horizontal corneal diameter ≥13 mm) with secondary glaucoma from spherophakia and/or ectopia lentis during childhood in affected Saudi families.

Methods: Clinical exam, homozygosity scan, and candidate gene analysis.

Results: From 2005 to 2010, eight affected individuals from three consanguineous families were identified. In addition to congenital megalocornea, affected children presented with secondary glaucoma from spherophakia and/or ectopia lentis. One member from each family developed spontaneous complete crystalline lens dislocation into the anterior chamber with associated acute glaucoma during early childhood. Older individuals had phenotypes that would have suggested prior uncontrolled primary congenital/infantile glaucoma had past ophthalmic and/or family histories not been available. Homozygosity mapping performed for the first two families suggested the candidate gene latent transforming growth factor-beta-binding protein 2 (LTBP2), which when sequenced revealed a novel homozgyous mutation that segregated with the phenotype in each family (p.S338PfsX4 [c.1012delT], p.Q1619X[(c.4855C>T]). LTBP2 sequencing in the third family revealed a third novel homozygous mutation (p.C1438Y [c.4313G>A]).

Conclusions: Congenital megalocornea with childhood secondary glaucoma from spherophakia and/or ectopia lentis is a distinct condition caused by recessive LTBP2 mutations that needs to be distinguished from buphthalmos secondary to primary congenital/infantile glaucoma because typical initial surgical treatment is lens removal in the former and angle surgery in the latter. Complete dislocation of the crystalline lens into the anterior chamber during early childhood can occur in young children with this unique phenotype.

Show MeSH
Related in: MedlinePlus