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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 3: two affected brothers, affected paternal aunt. A: At one and one-half year of age, the proband developed left acute pupillary block glaucoma. Complete crystalline lens dislocation into the anterior chamber of the left eye and a large corneal diameter (14 mm horizontally) can be seen. B: The proband's six-month-old brother was tentatively scheduled for primary congenital glaucoma surgery by his physician. Megalocornea is evident (14 mm horizontal diameter without breaks or scarring). The child also had bilateral spherophakia (not shown). C: The paternal aunt of the proband had been diagnosed with glaucoma at ten years of age but never had surgery. At 20 years old, bilateral symmetric megalocornea (14 mm horizontal diameter without breaks or scarring) is evident. Both crystalline lenses were posteriorly dislocated (not shown). She had high intraocular pressure, angle synechiae, and glaucomatous optic nerve damage in her right eye (not shown).
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f4: Family 3: two affected brothers, affected paternal aunt. A: At one and one-half year of age, the proband developed left acute pupillary block glaucoma. Complete crystalline lens dislocation into the anterior chamber of the left eye and a large corneal diameter (14 mm horizontally) can be seen. B: The proband's six-month-old brother was tentatively scheduled for primary congenital glaucoma surgery by his physician. Megalocornea is evident (14 mm horizontal diameter without breaks or scarring). The child also had bilateral spherophakia (not shown). C: The paternal aunt of the proband had been diagnosed with glaucoma at ten years of age but never had surgery. At 20 years old, bilateral symmetric megalocornea (14 mm horizontal diameter without breaks or scarring) is evident. Both crystalline lenses were posteriorly dislocated (not shown). She had high intraocular pressure, angle synechiae, and glaucomatous optic nerve damage in her right eye (not shown).

Mentions: A one and one-half year old boy presented to the emergency department with a three-day history of eye pain OS and irritability. Prior to presentation he had had episodes of left red painful eye on and off over the preceding few months. He had a history of large corneas since birth and a family history for congenital glaucoma in his younger brother, his father, and three of his father's siblings. Birth history was unremarkable and the child was otherwise normal by history. Parents were first cousins. The child could not be examined while awake because of irritability and thus examination was performed under chloral hydrate sedation. He did not have dysmorphic features or habitus. Ophthalmic examination was significant OD for 13 mm horizontal corneal diameter (without breaks or scarring) and inferonasal lens subluxation. Ophthalmic examination OS was significant for conjunctival injection, a 13 mm corneal diameter, corneal edema and central scarring, and complete crystalline lens dislocation into the anterior chamber causing pupillary block (Figure 4A). By the pneumotonometer (Model 30 Classic; Mentor, Norwell, MA) IOP was 15 mmHg OD and 54 mmHg OS. The child underwent emergent bilateral lensectomy and anterior vitrectomy. Three months post-operatively the child was comfortable, Tonopen IOP was 15 mmHg in both eyes, aphakic refraction was +18 D in both eyes, and optic nerve heads were healthy without cupping in both eyes. Homocystinuria screening was negative. For one year post-operatively he has not had 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 3: two affected brothers, affected paternal aunt. A: At one and one-half year of age, the proband developed left acute pupillary block glaucoma. Complete crystalline lens dislocation into the anterior chamber of the left eye and a large corneal diameter (14 mm horizontally) can be seen. B: The proband's six-month-old brother was tentatively scheduled for primary congenital glaucoma surgery by his physician. Megalocornea is evident (14 mm horizontal diameter without breaks or scarring). The child also had bilateral spherophakia (not shown). C: The paternal aunt of the proband had been diagnosed with glaucoma at ten years of age but never had surgery. At 20 years old, bilateral symmetric megalocornea (14 mm horizontal diameter without breaks or scarring) is evident. Both crystalline lenses were posteriorly dislocated (not shown). She had high intraocular pressure, angle synechiae, and glaucomatous optic nerve damage in her right eye (not shown).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: Family 3: two affected brothers, affected paternal aunt. A: At one and one-half year of age, the proband developed left acute pupillary block glaucoma. Complete crystalline lens dislocation into the anterior chamber of the left eye and a large corneal diameter (14 mm horizontally) can be seen. B: The proband's six-month-old brother was tentatively scheduled for primary congenital glaucoma surgery by his physician. Megalocornea is evident (14 mm horizontal diameter without breaks or scarring). The child also had bilateral spherophakia (not shown). C: The paternal aunt of the proband had been diagnosed with glaucoma at ten years of age but never had surgery. At 20 years old, bilateral symmetric megalocornea (14 mm horizontal diameter without breaks or scarring) is evident. Both crystalline lenses were posteriorly dislocated (not shown). She had high intraocular pressure, angle synechiae, and glaucomatous optic nerve damage in her right eye (not shown).
Mentions: A one and one-half year old boy presented to the emergency department with a three-day history of eye pain OS and irritability. Prior to presentation he had had episodes of left red painful eye on and off over the preceding few months. He had a history of large corneas since birth and a family history for congenital glaucoma in his younger brother, his father, and three of his father's siblings. Birth history was unremarkable and the child was otherwise normal by history. Parents were first cousins. The child could not be examined while awake because of irritability and thus examination was performed under chloral hydrate sedation. He did not have dysmorphic features or habitus. Ophthalmic examination was significant OD for 13 mm horizontal corneal diameter (without breaks or scarring) and inferonasal lens subluxation. Ophthalmic examination OS was significant for conjunctival injection, a 13 mm corneal diameter, corneal edema and central scarring, and complete crystalline lens dislocation into the anterior chamber causing pupillary block (Figure 4A). By the pneumotonometer (Model 30 Classic; Mentor, Norwell, MA) IOP was 15 mmHg OD and 54 mmHg OS. The child underwent emergent bilateral lensectomy and anterior vitrectomy. Three months post-operatively the child was comfortable, Tonopen IOP was 15 mmHg in both eyes, aphakic refraction was +18 D in both eyes, and optic nerve heads were healthy without cupping in both eyes. Homocystinuria screening was negative. For one year post-operatively he has not had 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