Erik Massenzio, MD
Wills Eye Hospital, Philadelphia, PA
Dr. Raziyeh Mahmoudzadeh, MD from Virginia Commonwealth University presented a patient with bilateral optic nerve pallor, severely hypoattenuated vessels, featureless fundus, and a hypopigmented ring in the macula of both eyes with thinning of the outer nuclear layer. Genetic testing revealed a pathogenic mitochondrial gene usually associated with non-syndromic hearing loss. Dr. Mahmoudzadeh then discussed the emerging classifications for mitochondrial diseases affecting the retina.
Dr. Efrat Naaman, MD from Harvard Medical School presented a patient with cerebral palsy who presented with left homonymous inferior quadrantanopia. The fundus autofluorescence showed abnormal hyperautofluorescence in the perimacular area. On family history, the patient’s mother had osteoarthritis, diabetes, and hearing loss. The patient’s mother was examined and found to have similar fundoscopic findings. Genetic testing revealed a point mutation in the MT-TL1 gene with 50% heteroplasmy, confirming the diagnosis of Maternally Inherited Diabetes and Deafness (MIDD) syndrome. Dr. Naaman discussed the significant challenges to making a diagnosis when retinal findings are the presenting signs.
Roselind L. Ni, BS, from Sidney Kimmel Medical College presented a patient with hyperpigmentation of the peripheral retina and underdeveloped foveal contour on OCT. The patient’s father was also examined in clinic with similar findings. Genetic testing revealed BEST1 deletion in exons 10 and 11. Diagnosis of autosomal dominant vitreoretinochoriodopathy was made, also known as ADVIRC. The hallmark features are circumferential well demarcated pigmentation of the peripheral retina. Dr. Pulido discussed that ADVIRC is a unique condition because the genetic variant is actually a gain of function mutation where the phagocytosis functionality of the RPE is enhanced, unlike in autosomal recessive Best disease where the RPE has poor phagocytosis. The discussion continued further to discuss whether gene therapy should be performed in a patient with Best disease who sees well currently but is expected to progress in the future, certainly an interesting topic in today’s day and age.
Nathalie Perez, MD from Wills Eye presented a patient with minimal fundus findings except for isolated thinning of the ONL and EZ in the foveal region without loss of the RPE. Dr. Perez shared that these OCT findings are highly suspicious for a cone photoreceptor dystrophy, and the panelists shared their differential diagnosis. The patient’s broad based gait abnormality helped narrow the differential. Genetic testing revealed a mutation in ATXN7 which confirmed the diagnosis of Cerebellar Ataxia type 7. Dr. Perez noted that this is a disease which exhibits anticipation phenomena, which describes successive generations showing earlier symptom onset and more disease progression due to continuous trinucleotide repeat expansions.
Vikram E. Ponnusamy, MD from NJ Retina presented a case of ciliopathy in Jeune syndrome, also known as asphyxiating thoracic dystrophy. Jeune syndrome is an osteogenic malformation causing a small, narrow chest. Respiratory distress leads to up to 80% infant mortality. If the patient survives, they will end up developing ciliopathy problems, including renal, hepatic, pancreatic, and ocular complications. For this reason, it usually presents as a rod-cone dystrophy. This case highlighted the embryonic origins of the retina and how it relates to systemic ciliopathy.
Haroon Rasheed, MD from the University of Southern California presented a 17 year old male with coordination difficulties, sensory loss, gastroparesis, and decompensation after a viral illness. Multimodal imaging revealed RPE atrophy around the arcades. MRI brain showed restricted diffusion in the bilateral cerebellar hemispheres, and conduction studies showed findings consistent with a peripheral neuropathy.
Initial genetic testing found a variant in SPTLC2, but whole genome sequencing found a mitochondrial variant leading to a diagnosis of NARP/MILS overlap syndrome (Neuropathy, Ataxia, RP)/ (Maternally Inherited Leigh syndrome). The mitochondrial component explained the decompensation after illness. The case highlights that initial genetic testing sometimes is not enough, and to consider further genetic testing if an overlap syndrome is suspected.
