Two neurologic facets of CTLA4-related haploinsufficiency
Xavier Ayrignac, Radjiv Goulabchand, Éric Jeziorski, P. Rullier, Clarissa Carra-Dallière, Claire Lozano, Pierre Portalès, Thierry Vincent, Jean‐François Viallard, Nicolas Menjot de Champfleur, Frédéric Rieux‐Laucat, Caroline Besnard, Michel Koenig, Claire Guissart, Pierre Labauge, Philippe Guilpain
Abstract
<h3>Objective</h3> To describe the clinical and radiologic neurologic characteristics of patients with cytotoxic T-lymphocyte antigen-4 (<i>CTLA4</i>) haploinsufficiency. <h3>Methods</h3> Three patients from 2 families had neurologic manifestations in the context of <i>CTLA4</i> haploinsufficiency. Their clinical and MRI findings are presented. <h3>Results</h3> A 16-year-old boy with a previous diagnosis of combined immunodeficiency presented with severe recurrent episodes of headaches, motor deficit, and seizures associated with waxing and waning gadolinium-enhancing FLAIR cortical/juxtacortical hyperintensities. His sister, who also had combined immunodeficiency, had a brain MRI when she was aged 13 years due to recent headaches and transient right hemianopsia. It revealed a gadolinium-enhancing left occipital white matter hyperintensity. Another 49-year-old woman had progressive visual loss and cerebellar ataxia in the context of recurrent pulmonary infections. All 3 patients were found to have inherited <i>CTLA4</i> haploinsufficiency. Patient 19s general condition and neurologic manifestations were completely controlled with abatacept (CTLA4-Ig). <h3>Conclusions</h3> These cases suggest that in addition to the variable clinical penetrance and wide spectrum of <i>CTLA4</i> haploinsufficiency, its neurologic spectrum is broad, ranging from recurrent tumefactive lesions to progressive deficits including cerebellar ataxia and optic atrophy with leukoencephalopathy. These phenotypes must be recognized, and should lead to a complete immunologic workup, because potentially effective targeted immunotherapy exists.