Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Neurology
Published in: BMC Neurology 1/2022

Open Access 01-12-2022 | Case report

Leukoencephalopathy with brain calcifications and cysts (Labrune syndrome) case report: diagnosis and management of a rare neurological disease

Authors: Michelle Paff, Nardin Samuel, Noor Alsafwani, Darcia Paul, Phedias Diamandis, Seth A. Climans, Walter Kucharczyk, Mandy Yi Rong Ding, Andrew F. Gao, Andres M. Lozano

Published in: BMC Neurology | Issue 1/2022

Login to get access

Abstract

Background

Leukoencephalopathy with brain calcifications and cysts (LCC; also known as Labrune syndrome) is a rare genetic microangiopathy caused by biallelic mutations in SNORD118. The mechanisms by which loss-of-function mutations in SNORD118 lead to the phenotype of leukoencephalopathy, calcifications and intracranial cysts is unknown.

Case presentation

We present the histopathology of a 36-year-old woman with ataxia and neuroimaging findings of diffuse white matter abnormalities, cerebral calcifications, and parenchymal cysts, in whom the diagnosis of LCC was confirmed with genetic testing. Biopsy of frontal white matter revealed microangiopathy with small vessel occlusion and sclerosis associated with axonal loss within the white matter.

Conclusions

These findings support that the white matter changes seen in LCC arise as a consequence of ischemia rather than demyelination.
Literature
1.
Labrune P, Lacroix C, Goutieres F, De Laveaucoupet J, Chevalier P, Zerah M, et al. Extensive brain calcifications, leukodystrophy, and formation of parenchymal cysts: a new progressive disorder due to diffuse cerebral microangiopathy. Neurology. 1996;46:1297–301.CrossRef
2.
Jenkinson EM, Rodero MP, Kasher PR, Uggenti C, Oojageer A, Goosey LC, et al. Mutations in SNORD118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts. Nat Genet. 2016;48:1185–92.CrossRef
3.
Corboy JR, Gault J, Kleinschmidt-Demasters BK. An adult case of leukoencephalopathy with intracranial calcifications and cysts. Neurology. 2006;67:1890–2.CrossRef
4.
Armstrong MJ, Hacein-Bey L, Brown H. Cerebroretinal microangiopathy with calcifications and cysts: demonstration of radiological progression. J Comput Assist Tomogr. 2009;33:571–2.CrossRef
5.
Chiang Y, Wang HJ, Chen CY. Adult-onset leukoencephalopathy, cerebral calcifications, and cysts: An 8-year neuroimaging follow-up of disease progression and histopathological correlation. J Clin Neurosci. 2019;69:276–9.CrossRef
6.
Marelli C, Savoiardo M, Fini N, Bartolomei I, Marliani AF, De Gonda F, et al. Late presentation of leucoencephalopathy with calcifications and cysts: report of two cases. J Neurol Neurosurg Psychiatry. 2008;79:1303–4.CrossRef
7.
Kaffenberger T, Valko PO, Von Meyenburg J, Barath K, Hewer E, Heppner FL, et al. A case of late onset leukoencephalopathy with cerebral calcifications and cysts in a 59-year-old woman. Eur J Neurol. 2009;16:278–81.CrossRef
8.
Ummer K, Salam KA, Noone ML, Pradeep Kumar VG, Mampilly N, Sivakumar S. Leukoencephalopathy with intracranial calcifications and cysts in an adult: Case report and review of literature. Ann Indian Acad Neurol. 2010;13:299–301.CrossRef
9.
Coeytaux A, Lobrinus JA, Horvath J, Kurian M, Vargas MI. Late onset of leucoencephalopathy with cerebral calcifications and cysts. J Neuroradiol. 2011;38:319–20.CrossRef
10.
Shtaya A, Elmslie F, Crow Y, Hettige S. Leukoencephalopathy, Intracranial Calcifications, Cysts, and SNORD118 Mutation (Labrune Syndrome) with Obstructive Hydrocephalus. World Neurosurg. 2019;125:271–2.CrossRef
11.
Stephani C, Pfeifenbring S, Mohr A, Stadelmann C. Late-onset leukoencephalopathy with cerebral calcifications and cysts: case report and review of the literature. BMC Neurol. 2016;16:19.CrossRef
12.
Crow YJ, Marshall H, Rice GI, Seabra L, Jenkinson EM, Baranano K, et al. Leukoencephalopathy with calcifications and cysts: genetic and phenotypic spectrum. Am J Med Genet A. 2021;185(1):15–25.CrossRef
13.
Osman O, Labrune P, Reiner P, Sarov M, Nasser G, Riant F, et al. Leukoencephalopathy with calcifications and cysts (LCC): 5 cases and literature review. Rev Neurol (Paris). 2020;176:170–9.CrossRef
14.
Briggs TA, Abdel-Salam GM, Balicki M, Baxter P, Bertini E, Bishop N, et al. Cerebroretinal microangiopathy with calcifications and cysts (CRMCC). Am J Med Genet A. 2008;146A:182–90.CrossRef
15.
Livingston JH, Mayer J, Jenkinson E, Kasher P, Stivaros S, Berger A, et al. Leukoencephalopathy with calcifications and cysts: a purely neurological disorder distinct from coats plus. Neuropediatric. 2014;45:175–82.CrossRef
16.
Tolmie JL, Browne BH, Mcgettrick PM, Stephenson JB. A familial syndrome with coats’ reaction retinal angiomas, hair and nail defects and intracranial calcification. Eye (Lond). 1998;2(3):297–303.CrossRef
17.
Polvi A, Linnankivi T, Kivela T, Herva R, Keating JP, Makitie O, et al. Mutations in CTC1, encoding the CTS telomere maintenance complex component 1, cause cerebroretinal microangiopathy with calcifications and cysts. Am J Hum Genet. 2012;90:540–9.CrossRef
18.
Livingston J, Mayer J, Jenkinson E, Kasher P, Stivaros S, Berger A, et al. Leukoencephalopathy with Calcifications and Cysts: A Purely Neurological Disorder Distinct from Coats Plus. Neuropediatrics. 2014;45:175–82.CrossRef
19.
Peculis BA. The sequence of the 5’ end of the U8 small nucleolar RNA is critical for 5.8S and 28S rRNA maturation. Mol Cell Biol. 1997;17:3702–13.CrossRef
20.
Badrock AP, Uggenti C, Wacheul L, Crilly S, Jenkinson EM, Rice GI, et al. Analysis of U8 snoRNA Variants in Zebrafish Reveals How Bi-allelic Variants Cause Leukoencephalopathy with Calcifications and Cysts. American journal of human genetic. 2020;106:694–706.CrossRef
21.
Sener U, Zorlu Y, Men S, Bayol U, Zanapalioglu U. Leukoencephalopathy, cerebral calcifications, and cysts. Am J Neuroradiol. 2006;27:200–3.PubMedPubMedCentral
22.
Ma Y, Zhang X, Cheng C, Xu Q, Di H, Zhao J, et al. Leukoencephalopathy with calcifications and cysts: A case report. Medicine. 2017;96:e7597.CrossRef
23.
Bonomo G, Monfrini E, Borellini L, Bonomo R, Arienti F, Saetti MC, et al. Systemic involvement in adult‐onset leukoencephalopathy with intracranial calcifications and cysts (Labrune syndrome) with a novel mutation of SNORD118 gene. Eur J Neurol. 2020;27(11):2329–32.CrossRef
24.
Nagae-Poetscher LM, Bibat G, Philippart M, Rosemberg S, Fatemi A, Lacerda MT, et al. Leukoencephalopathy, cerebral calcifications, and cysts: new observations. Neurology. 2004;62:1206–9.CrossRef
25.
Linnankivi T, Valanne L, Paetau A, Alafuzoff I, Hakumaki JM, Kivela T, et al. Cerebroretinal microangiopathy with calcifications and cysts. Neurology. 2006;67:1437–43.CrossRef
26.
Daglioglu E, Ergungor F, Hatipoglu HG, Okay O, Dalgic A, Orhan G, et al. Cerebral leukoencephalopathy with calcifications and cysts operated for signs of increased intracranial pressure: case report. Surg Neurol. 2009;72:177–81.CrossRef
27.
Kleinschmidt-Demasters BK, Cummings TJ, Hulette CM, Morgenlander JC, Corboy JR. Adult Cases of Leukoencephalopathy, Cerebral Calcifications, and Cysts: Expanding the Spectrum of the Disorder. J Neuropathol Exp Neurol. 2009;68:432–9.CrossRef
28.
Berry-Candelario J, Kasper E, Eskandar E, Chen CC. Neurosurgical management of leukoencephalopathy, cerebral calcifications, and cysts: A case report and review of literature. Surg Neurol Int. 2011;2:160.CrossRef
29.
Bertotti MM, Linhares MN, Ferreira R, Santos DS, Athayde AT Jr, Mussi ACM, et al. Leukoencephalopathy, cerebral calcifications, and cysts: entity that can mimic a neoplasm. Arq Neuropsiquiatr. 2011;69:717–22.CrossRef
30.
Pessoa AL, Monteiro Ado V, Queiroz RF, Malveira GL, Kok F. Leukoencephalopathy with cerebral calcifications and cyst: Labrune syndrome. Arq Neuropsiquiatr. 2012;70:230–1.CrossRef
31.
Banks GP, Weiss SA, Pisapia D, Willey JZ. A case of late-onset leukoencephalopathy, calcifications, and cysts presenting with intracerebral hemorrhage resembling a neoplasm. Cerebrovasc Dis. 2013;35:396–7.CrossRef
32.
Ooba H, Abe T, Hisamitsu Y, Fujiki M. Repeated cyst formation in a patient with leukoencephalopathy, cerebral calcifications, and cysts: effectiveness of stereotactic aspiration with Ommaya reservoir placement. J Neurosurg Pediatr. 2013;12:155–9.CrossRef
33.
Wang Y, Cheng G, Dong C, Zhang J, Meng Y. Adult-onset leukoencephalopathy, brain calcifications and cysts: a case report. J Med Case Rep. 2013;7:151.CrossRef
34.
Ogles RL, Joshi CL, Miller DC, Litofsky NS, Travis MD. Leukoencephalopathy, Cerebral Calcifications, and Cysts in Two Sisters. Pediatr Neurol. 2014;51:576–9.CrossRef
35.
Li Z, Han K, Yao W, Wei W, Li Y, Lan X. Adult-Onset Leukoencephalopathy with Calcifications and Cysts: Focusing on Hemorrhagic Propensity and Cysts Development. World Neurosurg. 2006;85(366):e9-13.
36.
Liu X, Zheng X, Sui Q, Xu W, Zee CS. Leukoencephalopathy with cerebral calcifications and cysts: clinical and pathological features in two adults. Acta Neurol Belg. 2016;116:47–52.CrossRef
37.
Wang M, Zhang M, Wu L, Dong Z, Yu S. Leukoencephalopathy with cerebral calcification and cysts: Cases report and literature review. J Neurol Sci. 2016;370:173–9.CrossRef
38.
Novo J, Lin D, Shanks M, Kocak M, Arvanitis L. A 55-year-old female with leukoencephalopathy with cerebral calcifications and cysts: Case report and radiopathologic description. Pathology - Research and Practice. 2017;213:1440–4.CrossRef
39.
Tamura R, Ohira T, Emoto K, Fujiwara H, Horikoshi T, Yoshida K. Leukoencephalopathy, cerebral calcifications, and cysts: A clinical case involving a long-term follow-up and literature review. J Neurol Sci. 2017;373:60–5.CrossRef
40.
Cullinane PW, Lynch SA, 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. Journal of Molecular Neuroscience. 2020;1–3.
Metadata
Title
Leukoencephalopathy with brain calcifications and cysts (Labrune syndrome) case report: diagnosis and management of a rare neurological disease
Authors
Michelle Paff
Nardin Samuel
Noor Alsafwani
Darcia Paul
Phedias Diamandis
Seth A. Climans
Walter Kucharczyk
Mandy Yi Rong Ding
Andrew F. Gao
Andres M. Lozano
Publication date
01-12-2022
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2022
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-021-02531-y

Other articles of this Issue 1/2022

BMC Neurology 1/2022 Go to the issue

Research

Endovascular recanalization of acute ischemic stroke patients exhibiting large vessel occlusion after pulmonary lobectomy: case series

Research

Development of a patient decision aid for discharge planning of hospitalized patients with stroke

Case report

Caspr2 antibodies in herpes simplex encephalitis: an extension of the spectrum of virus induced autoimmunity? – A case report

Case report

Opsoclonus-myoclonus syndrome associated with pancreatic neuroendocrine tumor: a case report

Case report

A case of ischemic stroke with hemorrhagic transformation associated with essential thrombocythemia and JAK-2 V617F mutation

Study protocol

Ipsilesional arm training in severe stroke to improve functional independence (IPSI): phase II protocol