A Case of Concurrent ADOA and HNPP: A Clinical Reminder of Hickam’s Dictum
Carlos Santos1, Jason Schick2, Aileen Antonio2, Paul Twydell3
1Department of Biomedical Engineering, College of Engineering, Wayne State University, 2Trinity Health Saint Mary's Hauenstein Neurosciences, 3Corewell Health
Objective:
To present a case of autosomal dominant optic atrophy (ADOA) in a patient with co-occurring hereditary neuropathy with liability to pressure palsy (HNPP).
Background:
ADOA is the most common hereditary optic neuropathy and is caused by mutations in the Optic Atrophy-1 (OPA1) gene. HNPP is a hereditary neuropathy caused by deletions in the peripheral myelin protein-22 (PMP22) gene.
Results:
A 46-year-old male presented with acute onset of left foot drop. History was significant for prior bilateral carpal tunnel syndrome and cubital tunnel syndrome. EMG was completed and suggestive of left peroneal neuropathy and an underlying diffuse sensorimotor polyneuropathy. Genetic testing revealed a deletion on chromosome 17p12, including the PMP22 gene, consistent with HNPP.
2 years later he presented with 4 years of slowly progressive bilateral vision loss. Neuro-ophthalmologic exam revealed dyschromatopsia and bilateral optic disc pallor. Optical coherence tomography showed severe retinal nerve fiber layer thinning of bilateral optic nerves (61 µm OD, 57 µm OS). MRI orbits confirmed symmetric optic nerve atrophy without compressive a compressive lesion, abnormal signal, or enhancement. Referral was placed to genetics, with exome sequencing showing a point mutation in the OPA1 gene (983 A>G), consistent with ADOA.
Conclusions:
ADOA and HNPP are among the most common heritable causes of optic atrophy and peripheral neuropathy, respectively. Neither condition has any significant phenotypic overlap; however, several conditions do exist where a single genetic mutation results in a phenotype of both optic atrophy and peripheral neuropathy (CMT2A, Familial Dysautonomia, etc.). To our knowledge, this is the first case reported of a patient presenting with peripheral neuropathy and bilateral optic atrophy due to both PMP22 and OPA1 genetic mutations, rather than possessing a single mutation known to cause both conditions. This case illustrates the counterargument to Occam’s razor, Hickam’s dictum.
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