Phenotypic Variability in Leukoencephalopathy with Brain Calcifications and Cysts: Case Report of Siblings from an Irish Traveller Family with a Homozygous SNORD118 Mutation

• Published in: Journal of molecular neuroscience Vol. 70; no. 9; pp. 1354 - 1356
• Main Authors: Cullinane, Patrick W., Lynch, Sally Ann, Marnane, Michael
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.09.2020; Springer Nature B.V
• Subjects: 3' Untranslated regions; Biomedical and Life Sciences; Biomedical materials; Biomedicine; Brain; Case reports; Cell Biology; Cysts; Emergency medical care; Emergency medical services; Epilepsy; Genetic screening; Genetic variability; Headache; Leukoencephalopathy; Medical imaging; Migraine; Mutation; Neurochemistry; Neuroimaging; Neurology; Neurosciences; Osteosarcoma; Patients; Phenotypes; Population genetics; Proteomics; Sarcoma; Siblings; Substantia alba; Variability; SNORD118; Cysts; Calcifications; Leukoencephalopathy
• ISSN: 0895-8696; 1559-1166
• DOI: 10.1007/s12031-020-01550-7

Leukoencephalopathy with brain calcifications and cysts (LCC) is a rare cerebral microangiopathy, the cause of which was recently determined to be recessively inherited mutations in the SNORD118 gene. We report the case of a 32-year-old Irish Traveller woman who presented to the emergency department in convulsive status epilepticus with abnormal neuroimaging features characteristic of LCC. Her medical history consisted of epilepsy, intellectual impairment, previous craniotomies for excision of cerebral cysts and resection of a tibial osteogenic sarcoma. Whole exome sequencing identified a previously described homozygous variant, NR_033294.1 n.*5C>G, in the 3′ UTR of the SNORD118 gene. Her sister was subsequently found to be homozygous for the same variant but with a significantly milder clinical phenotype consisting of migraine without aura and mild, non-specific, cerebral white matter changes on neuroimaging. Knowledge of the existence of LCC within this population means that targeted genetic testing for this specific mutation should be considered in Irish Traveller patients presenting with the characteristic clinical and radiological features. Given the striking phenotypic variability seen within this family, LCC should also be considered in Irish Traveller patients even in the absence of the complete radiological triad.