Optic nerve sheath distention in Leber's optic neuropathy and the significance of the "Wallace mutation"

Abstract

We recently encountered a 27-year-old man who presented an atypical clinical picture of Leber's hereditary optic neuropathy: His family history was negative, visual loss continued steadily for over 8 months, circumpapillary microangiopathy was equivocal, the optic discs showed large physiologic cups, and both optic nerve sheaths were notably distended with increased subarachnoid fluid. The latter was confirmed by ultrasonography, computed tomography, and magnetic resonance imaging. The patient's asymptomatic brother also showed unimpressive circumpapillary microangiopathy in the fundi. The asymptomatic mother from France was then seen, and she showed classic circumpapillary microangiopathy in the fundi. Studies of mitochondrial DNA showed the classic point mutation at position 11778 as reported by Wallace in all three family members. Another patient previously seen with classic Leber's hereditary optic neuropathy recently had mitochondrial DNA studies along with three other affected family members and five unaffected family members in the maternal lineage. All nine of these individuals were completely normal at the Wallace locus. In fact, sequencing of the entire ND-4 gene from one affected individual revealed it to be perfectly normal at the amino acid level. The importance of obtaining quantitative ultrasonography and the 30 degrees test, and studying mitochondrial DNA in patients suspected of having Leber's optic nerve disease is emphasized.