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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 2: two affected brothers. A: At six years of age, the proband developed right acute pupillary block glaucoma. Complete crystalline lens dislocation into the anterior chamber of the right eye can be seen. In the left eye, inferotemporal crystalline lens subluxation can be appreciated. Both corneas are symmetrically enlarged (14 mm horizontal diameter). B, C: The proband's brother had lens-related pupillary block glaucoma in the left eye for which he had bilateral lensectomy and anterior vitrectomy at four years of age. At ten years of age, glaucomatous cupping in the left eye (C) as opposed to the right eye (B) can be appreciated. Megalocornea (not shown) was symmetric (14 mm horizontal corneal diameters without scars or breaks).
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f3: Family 2: two affected brothers. A: At six years of age, the proband developed right acute pupillary block glaucoma. Complete crystalline lens dislocation into the anterior chamber of the right eye can be seen. In the left eye, inferotemporal crystalline lens subluxation can be appreciated. Both corneas are symmetrically enlarged (14 mm horizontal diameter). B, C: The proband's brother had lens-related pupillary block glaucoma in the left eye for which he had bilateral lensectomy and anterior vitrectomy at four years of age. At ten years of age, glaucomatous cupping in the left eye (C) as opposed to the right eye (B) can be appreciated. Megalocornea (not shown) was symmetric (14 mm horizontal corneal diameters without scars or breaks).

Mentions: A four-month old boy was referred for congenital glaucoma surgery. He had a history of large corneas since birth and a family history for childhood glaucoma in one of his two older brothers. Birth history was unremarkable and the child was otherwise normal without dysmorphic features or habitus. Parents were first cousins. The child could fixate well with either eye and there was no strabismus. There was occasional fine pendular low-amplitude high-frequency nystagmus. Ophthalmic examination was significant for megalocornea (14 mm horizontal diameter without breaks or scarring), bilateral iridonesis, and bilateral forward iris tenting by the lens (bilateral spherophakia). By the Tonopen IOP while the child was sleeping was 22 mmHg OD and 23 mmHg OS. Fundus examination was unremarkable; optic nerve heads were healthy without cupping. Retinoscopy was −22 D in both eyes and was prescribed as glasses. Homocystinuria urine screening was negative. At four years of age the child had bilateral lens subluxation within the pupil (inferotemporally OD and inferonasally OS) for which the refraction through the aphakic portion of the pupil of +16 D in both eyes. By the Tonopen IOP was 16 mmHg in both eyes. At six years of age the child presented with eye pain and redness OD, which the father complained was increasingly occurring on and off over the previous year. There was complete crystalline lens dislocation into the anterior chamber OD causing pupillary-block glaucoma (Figure 3A). The ectopic left crystalline lens was tenting the iris anteriorly. By the Tonopen IOP was 50 mmHg OD and 26 mmHg OS. Bilateral lensectomy with anterior vitrectomy was performed. Post-operatively the aphakic refraction was +15 D OD and +18 D OS and vertical cup-to-disc ratio was 0.4 OD and 0.3 OS. The child was fitted with aphakic glasses and was prescribed timolol 0.5% twice daily OD. Tonopen IOP has ranged in the low twenties for both eyes over a four-year post-operative period without evidence for glaucoma.


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 2: two affected brothers. A: At six years of age, the proband developed right acute pupillary block glaucoma. Complete crystalline lens dislocation into the anterior chamber of the right eye can be seen. In the left eye, inferotemporal crystalline lens subluxation can be appreciated. Both corneas are symmetrically enlarged (14 mm horizontal diameter). B, C: The proband's brother had lens-related pupillary block glaucoma in the left eye for which he had bilateral lensectomy and anterior vitrectomy at four years of age. At ten years of age, glaucomatous cupping in the left eye (C) as opposed to the right eye (B) can be appreciated. Megalocornea (not shown) was symmetric (14 mm horizontal corneal diameters without scars or breaks).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3: Family 2: two affected brothers. A: At six years of age, the proband developed right acute pupillary block glaucoma. Complete crystalline lens dislocation into the anterior chamber of the right eye can be seen. In the left eye, inferotemporal crystalline lens subluxation can be appreciated. Both corneas are symmetrically enlarged (14 mm horizontal diameter). B, C: The proband's brother had lens-related pupillary block glaucoma in the left eye for which he had bilateral lensectomy and anterior vitrectomy at four years of age. At ten years of age, glaucomatous cupping in the left eye (C) as opposed to the right eye (B) can be appreciated. Megalocornea (not shown) was symmetric (14 mm horizontal corneal diameters without scars or breaks).
Mentions: A four-month old boy was referred for congenital glaucoma surgery. He had a history of large corneas since birth and a family history for childhood glaucoma in one of his two older brothers. Birth history was unremarkable and the child was otherwise normal without dysmorphic features or habitus. Parents were first cousins. The child could fixate well with either eye and there was no strabismus. There was occasional fine pendular low-amplitude high-frequency nystagmus. Ophthalmic examination was significant for megalocornea (14 mm horizontal diameter without breaks or scarring), bilateral iridonesis, and bilateral forward iris tenting by the lens (bilateral spherophakia). By the Tonopen IOP while the child was sleeping was 22 mmHg OD and 23 mmHg OS. Fundus examination was unremarkable; optic nerve heads were healthy without cupping. Retinoscopy was −22 D in both eyes and was prescribed as glasses. Homocystinuria urine screening was negative. At four years of age the child had bilateral lens subluxation within the pupil (inferotemporally OD and inferonasally OS) for which the refraction through the aphakic portion of the pupil of +16 D in both eyes. By the Tonopen IOP was 16 mmHg in both eyes. At six years of age the child presented with eye pain and redness OD, which the father complained was increasingly occurring on and off over the previous year. There was complete crystalline lens dislocation into the anterior chamber OD causing pupillary-block glaucoma (Figure 3A). The ectopic left crystalline lens was tenting the iris anteriorly. By the Tonopen IOP was 50 mmHg OD and 26 mmHg OS. Bilateral lensectomy with anterior vitrectomy was performed. Post-operatively the aphakic refraction was +15 D OD and +18 D OS and vertical cup-to-disc ratio was 0.4 OD and 0.3 OS. The child was fitted with aphakic glasses and was prescribed timolol 0.5% twice daily OD. Tonopen IOP has ranged in the low twenties for both eyes over a four-year post-operative period without evidence for glaucoma.

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