O Osman1, P Labrune2, P Reiner1, M Sarov3, G Nasser4, F Riant5, E Tournier-Lasserve5, H Chabriat1, C Denier6. 1. Department of neurology, Lariboisière hospital, Assistance publique-Hôpitaux de Paris (AP-HP), 75010 Paris, France. 2. Department of pediatrics (PL), Béclère hospital, AP-HP, 92140 Clamart, France. 3. Department of neurology, Bicêtre hospital, AP-HP, 94270 Le Kremlin-Bicêtre, France. 4. Department of neuroradiology, Bicêtre hospital, AP-HP, 94270 Le Kremlin-Bicêtre, France. 5. Department of molecular genetics, Lariboisière hospital, AP-HP, 75010 Paris, France. 6. Department of neurology, Bicêtre hospital, AP-HP, 94270 Le Kremlin-Bicêtre, France; Paris-Sud university, Paris Saclay, 91400 Orsay, France. Electronic address: christian.denier@aphp.fr.
Abstract
INTRODUCTION: Leukoencephalopathy with calcifications and cysts (LCC) is a rare autosomal recessive cerebral angiomatous-like microangiopathy characterized by diffuse and asymmetric white-matter lesions associated with multiple calcifications and cysts. The disease is caused by SNORD118 mutations. The entire clinical spectrum of LCC is not yet fully determined. MATERIAL AND METHODS: To define the clinical spectrum of LCC, we analyzed data from recently diagnosed cases and from the litterature. Both clinical and imaging features from our five LCC cases harboring compound heterozygous SNORD118 mutations were presented and all cases reported in the litterature reviewed. RESULTS: Ninety-two LCC cases including our five patients were identified. Consanguinity was rare (4%), and 97% of cases were symptomatic. Mean age of first clinical manifestations was 16.1±16.1 years (range 1 month-71 years) and was earlier in men (10.3±14.3 years) than in women (20.2±22.8 years) (P=0.02). The main inaugural symptoms were seizures (36%; mean age at onset: 5.2±9.5 years) and progressive neurological symptoms including ataxia, dystonia and spasticity (26%; 27.8±23.6 years). Intracranial hypertension was less frequently observed (14%), mostly in adults (mean age 31.5±13.2 years). Ischemic or hemorrhagic strokes were inaugural symptoms in two adults (2%). During follow-up, most patients developed progressive extrapyramidal, cerebellar and pyramidal signs (83%), cognitive decline (56%), seizures (37%), intracranial hypertension (30%) or stroke (2%). CONCLUSION: In LCC, the clinical spectrum is largely heterogeneous and the course of the disease appears highly variable in contrast to other hereditary cerebral small vessel diseases.
INTRODUCTION:Leukoencephalopathy with calcifications and cysts (LCC) is a rare autosomal recessive cerebral angiomatous-like microangiopathy characterized by diffuse and asymmetric white-matter lesions associated with multiple calcifications and cysts. The disease is caused by SNORD118 mutations. The entire clinical spectrum of LCC is not yet fully determined. MATERIAL AND METHODS: To define the clinical spectrum of LCC, we analyzed data from recently diagnosed cases and from the litterature. Both clinical and imaging features from our five LCC cases harboring compound heterozygous SNORD118 mutations were presented and all cases reported in the litterature reviewed. RESULTS: Ninety-two LCC cases including our five patients were identified. Consanguinity was rare (4%), and 97% of cases were symptomatic. Mean age of first clinical manifestations was 16.1±16.1 years (range 1 month-71 years) and was earlier in men (10.3±14.3 years) than in women (20.2±22.8 years) (P=0.02). The main inaugural symptoms were seizures (36%; mean age at onset: 5.2±9.5 years) and progressive neurological symptoms including ataxia, dystonia and spasticity (26%; 27.8±23.6 years). Intracranial hypertension was less frequently observed (14%), mostly in adults (mean age 31.5±13.2 years). Ischemic or hemorrhagic strokes were inaugural symptoms in two adults (2%). During follow-up, most patients developed progressive extrapyramidal, cerebellar and pyramidal signs (83%), cognitive decline (56%), seizures (37%), intracranial hypertension (30%) or stroke (2%). CONCLUSION: In LCC, the clinical spectrum is largely heterogeneous and the course of the disease appears highly variable in contrast to other hereditary cerebral small vessel diseases.
Authors: Michelle Paff; Nardin Samuel; Andrew F Gao; Andres M Lozano; Noor Alsafwani; Darcia Paul; Phedias Diamandis; Seth A Climans; Walter Kucharczyk; Mandy Yi Rong Ding Journal: BMC Neurol Date: 2022-01-05 Impact factor: 2.474