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CASE REPORT
Year : 2021 | Volume
: 28
| Issue : 4 | Page : 257-259
Electrophysiological evaluation of fleck retina and temporal macular thinning in X-Linked alport's syndrome
Adel Al Akeely1, Patrik Schatz2, Amro Alhazimi3
1 Vitreoretinal Division, King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia
2 Vitreoretinal Division, King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia; Department of Ophthalmology, Clinical Sciences, Skane University Hospital, Lund University, Lund, Sweden
3 Department of Ophthalmology, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Kingdom of Saudi Arabia
Correspondence Address:
Dr. Adel Al Akeely
Vitreoretinal Division, King Khaled Eye Specialist Hospital, P.O. Box 7191, Riyadh 11462
Kingdom of Saudi Arabia
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/meajo.meajo_7_21
Abstract
We report a 39-year-old with Alport's syndrome. The patient presented with anterior lenticonus, cataract, and a corrected distance visual acuity of 20/25 and 20/60 in the right and left eyes, respectively. Fundus examination revealed generalized retinal flecks sparing the fovea in both eyes. Optical coherence topography showed temporal macular thinning. Normal fundus autofluorescence was observed in both eyes. Full-field electroretinography (ERG) demonstrated normal photopic and scotopic responses, while multifocal ERG showed no reduction of amplitudes generated from the temporal thinned macula, compared to the nasal macula, indicating preserved functional integrity of the retina.
Keywords: Alport's syndrome, COL4A5, fleck retina, full field electroretinography, multifocal electroretinography
Introduction 
Alport's syndrome is an inherited disease caused by mutations in the COL4A5 (X-linked, MIM# 303630) and/or COL4A3 or COL4A4 (autosomal recessive, MIM# 120070 and 120131, respectively) genes. This results in the absence of the type IV collagen α3α4α5 network.[1]
In the X-linked form, affected males develop renal failure and hearing loss. Ocular features include anterior and posterior lenticonus, posterior polymorphous corneal dystrophy, giant macular holes, temporal macular thinning, and dot-and-fleck retinopathy. The dot-and-fleck retinopathy tends to spare the perifoveal area and typically does not affect vision.[2] One study found that temporal macular thinning is more common than dot-and-fleck retinopathy, dull macular reflex, and anterior lenticonus in X-linked Alport's syndrome. In addition, this study considered an abnormal temporal thinning index in optical coherence topography (OCT) to be a potential biomarker of severe disease that culminates in early-onset renal failure.[2] Furthermore, OCT abnormalities revealed thinning of inner limiting membrane (ILM) and nerve fiber layer (NFL) and retinal pigment epithelium basement membrane of Bruch's membrane.[3]
Case Report We report a 39-year-old male kidney-transplant recipient secondary to Alport's syndrome. Three of the patient's brothers were affected by history, and all had received kidney transplants. The study was approved by the hospital institutional review board, and written informed consent was obtained.
The patient presented with anterior lenticonus, cataract, and a corrected distance visual acuity of 20/25 and 20/60 in the right and left eyes, respectively. His fundus examination revealed generalized retinal flecks sparing the fovea and dull foveal reflex in both eyes. The flecks did not appear on fundus autofluorescence imaging [Figure 1].
Figure 1: Photographs of the right eye of a male patient with X-linked Alport's syndrome and fleck retinopathy. (Top) Normal fundus autofluorescence. (Bottom) Wide-field imaging showing fleck retinopathyOCT showed temporal macular thinning. Full-field electroretinography (ffERG) demonstrated normal photopic and scotopic responses, while multifocal electroretinography (mfERG) showed a general reduction of amplitudes, but there was no significant reduction of amplitudes generated from the temporal thinned macula, compared to the nasal macula [Figure 2].
Figure 2: Testing of the right eye of a male patient with X-linked Alport's syndrome and fleck retinopathy. (Top) Optical coherence tomography showing temporal retinal thinning and a step-ladder macula. (Bottom) Multifocal electroretinographys amplitude plot (retinal view) demonstrates that there was a general reduction of amplitudes, but there was no significant reduction of amplitudes generated from the temporal thinned macula, compared to the nasal maculaNext-generation sequencing of known Alport's genes (COL4A3, COL4A4, and COL4A5) by Illumina HiSeq 1500 system (Bioscientia, Ingelheim, Germany) was performed, revealing a hemizygous deletion of one nucleotide at position c. 4177 in the exon 45 of COL4A5 (c. 4177delC). This leads to a frame shift and subsequent formation of a premature stop codon (p.Gln1393Lysfs*155). The frame shift mutation most probably results either in mRNA degradation by nonsense-mediated mRNA decay or the expression of a truncated and C-terminally highly anomalous collagen type IV alpha-5 chain. This mutation has been described in patients with Alport's syndrome and could be considered pathogenic.[4] The sequence change was validated with Sanger sequencing. Unfortunately, we were not able to obtain a medical report detailing the patient's auditory and renal functions, and his siblings were not available for ophthalmic evaluation.
Discussion Dot-and-fleck retinopathy in Alport's syndrome has been associated with COL4A5 mutation.[5] Temporal macular structural abnormalities have been described by OCT and electron microscopy.[3] To the best of our knowledge, no studies have described the functional effects produced by those structural changes. We report the functional effects of dot-and-fleck and temporal macular thinning in X-linked Alport's syndrome by means of ffERG and mfERG.
The normal ffERG response which measures the outer retinal function of the whole retina is in keeping with structural studies with OCT and electron microscopy which report abnormalities in the ILM and NFL with intact outer retinal layers and Bruch's membrane. Furthermore, mfERG showed no significant reduction of responses from the thinned temporal macula, compared to the nasal macula [Figure 2].
The normal fundus autofluorescence observed in the wide-field images in both eyes furthermore supports the overall preserved integrity of the outer retinal layers in this condition.
In X-linked Alport's syndrome, dot-and-fleck retinopathy and temporal macular thinning do not appear to affect the functional integrity of the retina.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References 
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