Abstract
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.
References
Gilbert E, Carmi S, Ennis S, Wilson JF, Cavalleri GL (2017) Genomic insights into the population structure and history of the Irish travellers. Sci Rep 7:1–12
Jenkinson EM, Rodero MP, Kasher PR, Uggenti C, Oojageer A, Goosey LC, Rose Y, Kershaw CJ, Urquhart JE, Williams SG, Bhaskar SS, O’Sullivan J, Baerlocher GM, Haubitz M, Aubert G, Barañano KW, Barnicoat AJ, Battini R, Berger A, Blair EM, Brunstrom-Hernandez JE, Buckard JA, Cassiman DM, Caumes R, Cordelli DM, De Waele LM, Fay AJ, Ferreira P, Fletcher NA, Fryer AE, Goel H, Hemingway CA, Henneke M, Hughes I, Jefferson RJ, Kumar R, Lagae L, Landrieu PG, Lourenço CM, Malpas TJ, Mehta SG, Metz I, Naidu S, Õunap K, Panzer A, Prabhakar P, Quaghebeur G, Schiffmann R, Sherr EH, Sinnathuray KR, Soh C, Stewart HS, Stone J, Van Esch H, Van Mol CEG, Vanderver A, Wakeling EL, Whitney A, Pavitt GD, Griffiths-Jones S, Rice GI, Revy P, Van Der Knaap MS, Livingston JH, O’Keefe RT, Crow YJ (2016) Mutations in SNORD118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts. Nat Genet 48:1185–1192
Livingston J, Mayer J, Jenkinson E, Kasher P, Stivaros S, Berger A, Cordelli D, Ferreira P, Jefferson R, Kutschke G, Lundberg S, Ounap K, Prabhakar P, Soh C, Stewart H, Stone J, van der Knaap M, van Esch H, van Mol C, Wakeling E, Whitney A, Rice G, Crow Y (2014) Leukoencephalopathy with calcifications and cysts: a purely neurological disorder distinct from coats plus. Neuropediatrics 45:175–182
Lynch SA, Crushell E, Lambert DM, Byrne N, Gorman K, King MD, Green A, O’Sullivan S, Browne F, Hughes J, Knerr I, Monavari AA, Cotter M, McConnell VPM, Kerr B, Jones SA, Keenan C, Murphy N, Cody D, Ennis S, Turner J, Irvine AD, Casey J (2018) Catalogue of inherited disorders found among the Irish Traveller population. J Med Genet 55:233–239
Ma Y, Zhang X, Cheng C, Xu Q, Di H, Zhao J, Huang D, Yu S (2017) Leukoencephalopathy with calcifications and cysts: a case report. Medicine (Baltimore) 96:e7597
McGovern M, Flanagan O, Lynch B, Lynch SA, Allen NM (2017) Novel COL4A2 variant in a large pedigree: consequences and dilemmas. Clin Genet 92:447–448
Wang M, Zhang M, Wu L, Dong Z, Yu S (2016) Leukoencephalopathy with cerebral calcification and cysts: cases report and literature review. J Neurol Sci 370:173–179
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All authors contributed to the study conception and design. Patrick Cullinane wrote the first draft of the manuscript, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Cullinane, P.W., Lynch, S.A. & Marnane, M. Phenotypic Variability in Leukoencephalopathy with Brain Calcifications and Cysts: Case Report of Siblings from an Irish Traveller Family with a Homozygous SNORD118 Mutation. J Mol Neurosci 70, 1354–1356 (2020). https://doi.org/10.1007/s12031-020-01550-7
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DOI: https://doi.org/10.1007/s12031-020-01550-7