A Novel Mutation Confirms MFRP as the Gene Causing the Syndrome of Nanophthalmos–Renititis Pigmentosa–Foveoschisis–Optic Disk Drusen

Crespí, Jaume; Buil, José A.; Bassaganyas, Francisca; Segarra, José; Díaz-Cascajosa, Jesús; Ayala-Ramírez, Raúl; Zenteno, Juan Carlos

doi:10.1016/j.ajo.2008.04.029

Cited by 87 publications

(66 citation statements)

References 17 publications

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“…39 Calcium deposits within the optic nerve axonal mitochondria and the extracellular space lead to optic disc drusen. 40 Retinitis pigmentosa accompanied by optic disc drusen also has been reported in association with mutations in the MFRP gene, where it is accompanied by (posterior) microphthalmos and high hyperopia, 41,42 as well as in some reports of Usher syndrome. 43 An earlier study showed an incidence of optic disc drusen or parapapillary drusen of 9.2% in autosomal dominant, autosomal recessive, and X-linked recessive types of RP, 44 indicating that optic disc drusen are not a unique feature of CRB1-associated retinal dystrophies.…”

Section: Discussionmentioning

confidence: 99%

Genotypic and Phenotypic Characteristics of CRB1 -Associated Retinal Dystrophies

et al. 2017

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Purpose: To describe the phenotype, long-term clinical course, clinical variability, and genotype of patients with CRB1-associated retinal dystrophies.Design: Retrospective cohort study. Participants: Fifty-five patients with CRB1-associated retinal dystrophies from 16 families. Methods: A medical record review of 55 patients for age at onset, medical history, initial symptoms, bestcorrected visual acuity, ophthalmoscopy, fundus photography, full-field electroretinography (ffERG), Goldmann visual fields (VFs), and spectral-domain optical coherence tomography.Main Outcome Measures: Age at onset, visual acuity survival time, visual acuity decline rate, and electroretinography and imaging findings.Results: A retinitis pigmentosa (RP) phenotype was present in 50 patients, 34 of whom were from a Dutch genetic isolate (GI), and 5 patients had a Leber congenital amaurosis phenotype. The mean follow-up time was 15.4 years (range, 0e55.5 years). For the RP patients, the median age at symptom onset was 4.0 years. In the RP group, median ages for reaching low vision, severe visual impairment, and blindness were 18, 32, and 44 years, respectively, with a visual acuity decline rate of 0.03 logarithm of the minimum angle of resolution per year. The presence of a truncating mutation did not alter the annual decline rate significantly (P ¼ 0.75). Asymmetry in visual acuity was found in 31% of patients. The annual VF decline rate was 5% in patients from the genetic isolate, which was significantly faster than in non-GI patients (P < 0.05). Full-field electroretinography responses were extinguished in 50% of patients, were pathologically attenuated without a documented rod or cone predominance in 30% of patients, and showed a rodecone dysfunction pattern in 20% of RP patients. Cystoid fluid collections in the macula were found in 50% of RP patients.Conclusions: Mutations in the CRB1 gene are associated with a spectrum of progressive retinal degeneration. Visual acuity survival analyses indicate that the optimal intervention window for subretinal gene therapy is within the first 2 to 3 decades of life. Ophthalmology 2017;124:884-895 ª 2017 by the American Academy of Ophthalmology Supplemental material available at www.aaojournal.org.Mutations in the CRB1 gene are associated with a wide variety of severe retinal dystrophies with variable phenotypes, including panretinal dystrophies such as retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), and coneerod dystrophy, as well as central phenotypes such as isolated macular dystrophy and foveal retinoschisis. Retinitis pigmentosa is a clinically and genetically heterogeneous disorder. Mutations in the CRB1 gene have been associated with RP12, a distinct form of RP characterized by preservation of para-arteriolar retinal pigment epithelium, progressive visual field (VF) loss starting from the first decade of life, and early macular involvement. 4 Other common features are hyperopia and optic disc drusen, previously described in a Dutch genetic isolate (GI). 5Classic forms of earl...

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Section: Discussionmentioning

confidence: 99%

Genotypic and Phenotypic Characteristics of CRB1 -Associated Retinal Dystrophies

et al. 2017

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“…The association of pigmentary retinopathy with microphthalmos (both NO and PM) has been well documented in case reports and case series. 20,21 Cases of syndromes of pigmentary retinopathy, optic disk drusen, and foveoschisis with both entities of PM and NO 7,22 are also reported but were not seen in our current series of cases. Familial association of pigmentary retinopathy has been reported rarely.…”

Section: Discussionmentioning

confidence: 56%

“…Various studies published at different time points have used different and sometimes overlapping biometric criteria to define these two clinical entities. [6][7][8][9][10][11][12][13][14][15][16] We used a single measurement of horizontal corneal diameter of o11 mm for differentiating NO from PM in simple microphthalmic eyes with axial length of o20.5 mm in our high-hyperopia cohort. Detailed biometry evaluation of the two groups revealed many interesting findings.…”

Section: Discussionmentioning

confidence: 99%

“…7 Various other ocular findings reported include microcornea, a high lens/eye volume ratio, angle-closure glaucoma (ACG), 8 yellow macular pigmentation, chorioretinal folds, macular hypoplasia, retinal cysts, 9 crowded optic discs, 9 retinal striae and folds, 10 wrinkling of ILM, 11 thickened sclera with abnormal collagen fibrils, 12 recurrent or persistent choroidal effusions, 2,6 and non-rhegmatogenous retinal detachments. 11 Eyes with short axial length but normal corneal diameter were first reported in 1975 13 and the term 'PM' was introduced to differentiate these patients from NO that have small corneal diameter.…”

Section: Introductionmentioning

confidence: 99%

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High-hyperopia database, part I: clinical characterisation including morphometric (biometric) differentiation of posterior microphthalmos from nanophthalmos

Relhan

Jalali

Pehre

et al. 2015

Eye

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Purpose To characterise and differentiate posterior microphthalmos (PM) and nanophthalmos (NO) using morphometric parameters. Patients and methods Consecutive case database of patients with hyperopia 4+7.00 D sphere was analysed retrospectively for clinical and biometric characterisation. Thirtyeight consecutive high-hyperopic subjects (75 eyes) with axial lengths o20.5 mm underwent uniform comprehensive ocular evaluation. Twenty-five subjects were diagnosed as PM and 13 as NO based on the horizontal corneal diameter. Parameters analysed included visual acuity, refraction, horizontal corneal diameter, anterior chamber depth, lens thickness, axial length, fundus changes, and associated ocular pathology. Primary outcome measures: ocular biometry difference between PM and NO. Secondary outcome measures: differences in associated ocular pathologies between PM and NO. Results Hyperopia ranged from +7 to +17 D and was similar in the two groups. Lens thickness was statistically more in NO than in PM group (4.53 ± 0.75 mm vs 3.82 ± 0.48 mm, P o0.001), whereas anterior chamber depth was more in the PM than in NO group (3.26 ± 0.36 mm, vs 2.59 ± 0.37 mm, Po0.001). NO had higher association with angle-closure glaucoma (66.7% vs 0%) and pigmentary retinopathy (38.5 vs 8.0%) but lesser association with macular folds (0% vs 24%) as compared with PM. NO was associated with poorer visual acuity.Conclusion PM and NO have significant differences in lens thickness, anterior chamber depth, prevalence of glaucoma, pigmentary retinopathy, macular pathology, and visual acuity while being similar in hyperopic refraction.

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“…11 Only missense variants have been found in GDF6 (MCOP4) 10,13 and GDF3 (MCOP7), 14 and are inherited in an autosomal-dominant manner. Homozygous or compound heterozygous variants in MFRP (MCOP5) [15][16][17][18][19] or PRSS56 (MCOP6) [20][21][22][23] are associated with autosomal-recessive posterior microphthalmia, which defines a rare distinct phenotype restricted primarily to the posterior segment of the eye. Patients with MFRP variants also develop a progressive rod cone dystrophy.…”

Section: Mutational Spectrummentioning

confidence: 99%

Clinical utility gene card for: Non-Syndromic Microphthalmia Including Next-Generation Sequencing-Based Approaches

Richardson¹,

Sowden²,

Gerth‐Kahlert

et al. 2017

Eur J Hum Genet

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A Novel Mutation Confirms MFRP as the Gene Causing the Syndrome of Nanophthalmos–Renititis Pigmentosa–Foveoschisis–Optic Disk Drusen

Cited by 87 publications

References 17 publications

Genotypic and Phenotypic Characteristics of CRB1 -Associated Retinal Dystrophies

Genotypic and Phenotypic Characteristics of CRB1 -Associated Retinal Dystrophies

High-hyperopia database, part I: clinical characterisation including morphometric (biometric) differentiation of posterior microphthalmos from nanophthalmos

Clinical utility gene card for: Non-Syndromic Microphthalmia Including Next-Generation Sequencing-Based Approaches

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