Novel CHRLD1 Mutation and Secondary Glaucoma in Patient with X-Linked Megalocornea

Abstract

 

Purpose

 

X-linked megalocornea (MGC1) is a bilateral developmental disorder of the anterior segment with enlarged, thin corneas,extremely deep anterior chambers (AC), and normal intraocular pressures (IOPs). Associated ocular features include mosaic corneal degeneration, iris atrophy/pigment dispersion, lens dislocation, and cataract. MGC1 has been recently been mapped to the Chordin-like 1 gene (CHRDL1) encoding for ventropin. A 63 year-old male with MGC1 presented to the Cornea Service 5 months after secondary placement of iris fixated posterior chamber intraocular lens (IOL). Our purpose is to present the clinical course of this patient with MGC1 and genotyping results in his family.

 

Methods

 

We performed a retrospective chart review to describe ocular findings and clinical course of subject with MGC1. PCR amplification and traditional Sanger sequencing the 11 coding exons of CHRDL1 were performed on genomic DNA from proband and siblings.

 

Results

 

Slit lamp findings of our subject included bilateral, enlarged corneas with mosaic degeneration, extremely deep AC, iris trans-illumination defects, and increased pigment in irido-corneal angles. Central corneal pachymetery measured 498 µm OD and 517 µm OS. The patient had had cataract extraction 20 years previously and had been left aphakic OU. Five months before presentation, the patient underwent secondary placement of an iris-fixated IOL in OS. IOPs were 13 mmHg OD and 24 mmHg OS despite 3 glaucoma medications. Right optic nerve had a 0.15 and left had 0.8 cup/disc ratios respectively. Four months after explantation of IOL, the patient underwent placement of a Baerveldt glaucoma implant for refractory glaucoma. A novel CHRDL1 mutation was found in exon 10 of proband (chrX 109,811,419 (hg19), c.1097delT, p.Leu366ArgfsX7). This single nucleotide deletion is predicted to result in a frameshift mutation and premature stop codon.

 

Conclusions

 

Although elevated IOP is not a feature of MGC1, these eyes may be more prone to secondary glaucoma. Our reported novel mutation in CHRLD1 expands the mutational spectrum of this disorder. Our family further establishes that the disorder is genetically homogenous as the seven other families recently reported also all had mutations in CHRDL1.

 

 

Slit lamp photo of aphakic right eye with enlarged corneal diameter and patchy iris stromal defects.

 

 

Left eye with iris fixated IOL. Note corneal mosaic degeneration centrally.

 

Keywords: 479 cornea: clinical science • 494 degenerations/dystrophies • 539 genetics