Pulmonary Arterial Hypertension With Moyamoya Disease Harboring the RNF213 p.Arg4810Lys Variant Presenting a Favorable Response to Monotherapy: A Case Report.

Pulmonary arterial hypertension (PAH) harboring the heterozygous ring finger protein 213 (RNF213) p.Arg4810Lys variant responds poorly to PAH treatment and has a poor prognosis. Here, we present a case of severe PAH and moyamoya disease (MMD) harboring a heterozygous RNF213 p.Arg4810Lys variant that responded well to PAH monotherapy. A 23-year-old woman with cerebral infarction due to MMD was referred to our center for MMD bypass surgery and treatment of severe PAH. Genetic analysis revealed a heterozygous RNF213 p.Arg4810Lys variant. We initiated PAH-targeted therapy before MMD bypass surgery, as bypass surgery was considered high-risk in the presence of severe PAH. Despite a positive response to acute vasoreactivity testing with nitric oxide (NO) inhalation, calcium channel blockers were avoided due to the risk of hypotension-induced cerebral ischemia. We initiated endothelin receptor antagonist (macitentan, 10 mg/day) monotherapy because upfront combination therapy may also cause hypotension. Endothelin receptor antagonist monotherapy improved symptoms and pulmonary hemodynamics, reducing vascular resistance from 11.4 to 7.1 Wood Units after 1 month. Bilateral cerebral bypass surgery was performed after hemodynamic improvement. The clinical spectrum of RNF213-associated PAH may be broader than previously reported. This case highlights the importance of personalized medicine that considers patient conditions and comorbidities when selecting treatment options for patients with PAH harboring the RNF213 p.Arg4810Lys variant.