Rod bipolar cell dysfunction in POLG retinopathy

Objective To report the clinical and novel electrophysiological features in a child withPOLG-related sensory ataxic neuropathy, dysarthria and ophthalmoparesis (SANDO). Methods The proband, a male child of Indian descent, underwent serial systemic and ophthalmological evaluations from birth until 14 years of age. Eye examinations included visual acuity and extraocular movement assessments, fundus photography, spectral domain optical coherence tomography and full-field electroretinography (ERG). Detailed genetic testing was also performed. Results The child carried a homozygous mutation inPOLG(c.911T > G/p.Leu304Arg) and manifested systemic features such as seizures, headaches, areflexia, hypotonia, myopathy and vomiting. The child's distance visual acuity was 0.50 and 0.40 LogMAR in the right and left eyes, respectively. Bilateral ophthalmoplegia and ptosis were observed at 5 years of age. The dark-adapted (DA) ERG responses to 2.29 cd s m(-2)and 7.6 cd s m(-2)stimuli showed a markedly reducedb/aratio; an electronegative configuration was noted to a DA 7.6 ERG. Conclusion This is the first documented case of an electronegative ERG in aPOLG-related disorder consistent with generalized rod ON-bipolar dysfunction. The rest of the proband's systemic and ophthalmological features were consistent with SANDO but some features overlapped with otherPOLG-related disorders such as Alpers-Huttenlocher syndrome and autosomal dominant progressive external ophthalmoplegia demonstrating the wide phenotypic overlap expected due toPOLGmutations.

Automated summary

This is the first documented case of an electronegative ERG in a POLG-related disorder, demonstrating wide phenotypic overlap. The patient exhibited systemic symptoms in addition to ophthalmological features and carried a homozygous mutation in POLG.