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RNA Biol 2022 31;19(1):412-418. Epub 2021 Dec 31.

Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.

Small nucleolar RNAs (snoRNAs) are non-coding RNAs vital for ribosomal RNA (rRNA) maturation. The U8 snoRNA, encoded by the gene in humans, is an atypical C/D box snoRNA as it promotes rRNA cleavage rather than 2'-O-methylation and is unique to vertebrates. The U8 snoRNA is critical for cleavage events that produce the mature 5. Read More

BMC Neurol 2022 Jan 5;22(1):10. Epub 2022 Jan 5.

Division of Neurosurgery, Department of Surgery, University Health Network, Toronto, ON, USA.

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. Read More

Indian J Radiol Imaging 2021 Jul 13;31(3):772-775. Epub 2021 Nov 13.

Department of Radiology, Lokmanya Tilak Municipal Medical College and General Hospital, Mumbai, Maharashtra, India.

Leukoencephalopathy, cerebral calcifications, and cysts (LCC) form a very rare association which is named as "Labrune syndrome" after Labrune who reported the first case in 1996. To the best of our knowledge only eight to 10 cases have been reported in literature to date. We report a case of a 26-year-old male with onset of neurological symptoms in late adolescence (at 19 years of age) and presented with complains of continued seizures for 7 years, giddiness with imbalance, and slowly progressive motor symptoms. Read More

Neurol India 2021 Jul-Aug;69(4):1116-1118

Department of Neurology, Bangur Institute of Neurosciences, IPGMER and SSKM Hospital, Kolkata, West Bengal, India.

Neurol Sci 2021 Nov 5;42(11):4471-4487. Epub 2021 Sep 5.

Neuroradiology Unit, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Viale Oxford 81, 00133, Rome, Italy.

Leukoencephalopathy with cerebral calcifications and cysts (LCC) is a neurological disorder characterized by the radiological triad of white matter abnormalities, intracranial calcifications and cystic lesions variable in size resulting from a diffuse cerebral microangiopathy. Typically, progressive focal neurological deficits and seizures are the first clinical manifestation, but the severity of symptoms can vary according to the size and location of the cystic lesions holding compressive effects on the surrounding brain tissue. The most common histopathological finding is diffuse microangiopathy, which might be associated to pathogenic mutations in SNORD118 gene causing Labrune syndrome. Read More

Childs Nerv Syst 2022 03 21;38(3):643-648. Epub 2021 May 21.

Department of Neurosurgery, Great Ormond Street Hospital NHS Foundation Trust, London, UK.

Ribosomopathies are rare, recently defined entities. One of these, Labrune syndrome, is recognisable radiologically by its distinctive triad of leukoencephalopathy, intracranial calcifications and cysts (LCC). These cysts may have neurosurgical implications at different ages because of their progressive expansion and local mass effect. Read More

Nat Commun 2021 04 20;12(1):2344. Epub 2021 Apr 20.

Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA, USA.

Direct determination of RNA structures and interactions in living cells is critical for understanding their functions in normal physiology and disease states. Here, we present PARIS2, a dramatically improved method for RNA duplex determination in vivo with >4000-fold higher efficiency than previous methods. PARIS2 captures ribosome binding sites on mRNAs, reporting translation status on a transcriptome scale. Read More

Brain Sci 2020 Nov 18;10(11). Epub 2020 Nov 18.

Department of Medical Genetics, Medical University of Warsaw, 02-106 Warsaw, Poland.

Leukoencephalopathy with calcifications and cysts (LCC) is a triad of neuroradiological symptoms characteristic of Labrune syndrome, which was first described in 1996. For 20 years, the diagnosis was only based on clinical, neuroradiological and histopathological findings. Differential diagnosis included a wide spectrum of diseases. Read More

Am J Med Genet A 2021 01 7;185(1):15-25. Epub 2020 Oct 7.

Department of Paediatric Neurology, University Hospital of Wales, Cardiff, UK.

Biallelic mutations in SNORD118, encoding the small nucleolar RNA U8, cause leukoencephalopathy with calcifications and cysts (LCC). Given the difficulty in interpreting the functional consequences of variants in nonprotein encoding genes, and the high allelic polymorphism across SNORD118 in controls, we set out to provide a description of the molecular pathology and clinical spectrum observed in a cohort of patients with LCC. We identified 64 affected individuals from 56 families. Read More

J Child Neurol 2021 02 28;36(2):133-140. Epub 2020 Sep 28.

Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Leukoencephalopathy with calcifications and cysts (LCC) is a neurological syndrome recently associated with pathogenic variants in . We report autopsy neuropathological findings from an individual with genetically confirmed LCC. Histologic studies included staining of formalin-fixed paraffin-embedded tissue sections by hematoxylin and eosin, elastic van Gieson, and luxol fast blue. Read More

Pediatr Neurol 2020 11 25;112:53-55. Epub 2020 Jul 25.

Genomic Unit, Health Research Institute La Fe (IIS La Fe), Valencia, Spain.

Childs Nerv Syst 2021 05 12;37(5):1765-1770. Epub 2020 Aug 12.

Department of Neurosurgery, Division of Pediatric Neurosurgery, Johns Hopkins School of Medicine, Baltimore, MD, USA.

Purpose: Labrune syndrome (LS) is a rare white matter disease characterized by leukoencephalopathy with intracranial calcification and cysts (LCC). While the intracranial cyst characteristics of LS are for the most part stable, some may require surgical intervention when they develop associated hemorrhage and/or mass effect. To date, no review of the surgical outcomes of cyst decompression in LS has been performed. Read More

Clin Nucl Med 2020 Oct;45(10):e439-e440

From the Departments of Nuclear Medicine.

A 69-year-old woman presented with cognitive impairment related to attentive, executive, and mnemonic functions; progressive worsening of walking, speaking, writing, and reading ability; and double sphincter incontinence. Leukoencephalopathy, cystic lesions, and calcifications, suspected for Labrune syndrome, were observed at MRI and CT brain images. Generalized wave abnormalities were also visible at electroencephalogram. Read More

Eur J Neurol 2020 11 2;27(11):2329-2332. Epub 2020 Jun 2.

Neurosurgery Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.

Background And Purpose: Although Labrune syndrome is a well-known disorder characterized by a typical neuroradiological triad, namely leukoencephalopathy, intracranial calcifications and cysts, there are no reports of systemic involvement in this disorder. This paper attempts to describe a peculiar clinical manifestation related to a novel mutation in the SNORD118 gene.

Methods: Clinical examination, brain and total-body imaging, and neurophysiological and ophthalmological investigations were performed. Read More

A A Pract 2020 May;14(7):e01212

From the Department of Anesthesiology and Pain Medicine, Seattle Children's, Seattle, Washington.

A 20-year-old man with a rare neurodegenerative disease developed hypermetabolic symptoms with dyskinesia after a third ventriculostomy for hydrocephalus. The initial presentation was concerning for an acute dystonic reaction after metoclopramide was administered for nausea. He concurrently developed hypermetabolic symptoms, including hyperthermia, tachycardia, and a lactic acidosis. Read More

J Mol Neurosci 2020 Sep 2;70(9):1354-1356. Epub 2020 May 2.

Department of Neurology, Mater Misericordiae University Hospital, Dublin, Ireland.

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. Read More

Am J Hum Genet 2020 05 30;106(5):694-706. Epub 2020 Apr 30.

Division of Evolution and Genomic Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, M13 9PT, UK. Electronic address:

How mutations in the non-coding U8 snoRNA cause the neurological disorder leukoencephalopathy with calcifications and cysts (LCC) is poorly understood. Here, we report the generation of a mutant U8 animal model for interrogating LCC-associated pathology. Mutant U8 zebrafish exhibit defective central nervous system development, a disturbance of ribosomal RNA (rRNA) biogenesis and tp53 activation, which monitors ribosome biogenesis. Read More

Neurology 2020 06 1;94(22):994-999. Epub 2020 May 1.

From the Departments of Neurology (J.W., M.R.B., R.H.T.), Clinical Neurophysiology (M.R.B.), and Infectious Disease (D.A.P.), Royal Victoria Infirmary; Institute of Neuroscience (M.R.B., R.H.T.), Newcastle-Upon-Tyne, UK; Institute of Neurosciences Kolkata (S.T., H.K.), India; Division of Evolution and Genomic Sciences (G.I.R.), School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre; Centre for Genomic and Experimental Medicine (Y.C.), MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, UK; and Laboratory of Neurogenetics and Neuroinflammation (Y.C.), Institut Imagine, Paris Descartes University, France.

J Clin Neurosci 2019 Nov 22;69:276-279. Epub 2019 Aug 22.

Department of Medical Imaging, Taipei Medical University Hospital, Taiwan; Translational Imaging Research Center, College of Medicine, Taipei Medical University, Taiwan.

Leukoencephalopathy, cerebral calcifications, and cysts (LCC) is an extremely rare neurological disease, also known as Labrune syndrome. The disease more commonly affects children and young adults and the characteristic triple imaging findings are leukoencephalopathy, calcifications and multiple cysts, presenting with a variety of supra- and infratentorial symptoms but lacking for extra-neurological manifestations. Coats plus syndrome and cerebroretinal microangiopathy with calcifications and cysts (CRMCC) share similar neurological findings with LCC, but additionally involves other extra-neurological organs. Read More

Neurol India 2019 May-Jun;67(3):934-935

Department of Neuro-Imaging and Interventional Neuro-Radiology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.

World Neurosurg 2019 05 19;125:271-272. Epub 2019 Feb 19.

Atkinson Morley Neurosurgery Centre, St. George's University Hospital NHS Foundation Trust, London, United Kingdom.

Labrune syndrome is a neurologic disorder that manifests as a progressive cerebral degeneration characterized by a radiologic triad of cerebral white matter disease (leukoencephalopathy), intracranial calcification, and cysts. The associated novel genetic mutation in SNORD118 has been recently identified. However, its significance in relation to the progression and severity of the disease is yet to be clarified. Read More

Eur J Neurol 2018 08;25(8):e88-e90

Hospital Infantil Albert Sabin, Universidade estadual do Ceará, Fortaleza, Ceará, Brazil.

Eur J Neurol 2018 08;25(8):e86-e87

Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.

Eur J Paediatr Neurol 2018 Sep 25;22(5):866-869. Epub 2018 Jun 25.

Department of Neurology (Paediatric Neurology) and Amalia Children's Hospital, Donders Centre for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands.

Leukoencephalopathy with brain calcifications and cysts (LCC) is a genetic white matter disorder, which involves the brain small blood vessels. In the absence of extra-neurological symptoms, LCC has a pathognomonic radiological phenotype. Recently, biallelic mutations in the SNORD118 gene, which is a non-protein coding gene, were discovered to cause LCC. Read More

eNeurologicalSci 2017 Sep 21;8:28-30. Epub 2017 Jul 21.

Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, 1-1 Yazakokarimata, Nagakute 480-1195, Japan.

Since she was 4 years old, the patient had exhibited frequent convulsive seizures, and she experienced severe headaches and depression in adulthood. At the age of 37 years, cerebral calcifications were detected, but she exhibited no cognitive or motor problems. She suffered a cerebral haemorrhage at 49 years old and experienced cognitive dysfunction, dysarthria, dysphagia, and left-hemiparesis as sequelae. Read More

Pathol Res Pract 2017 Nov 6;213(11):1440-1444. Epub 2017 Jul 6.

Rush University Medical Center, Department of Pathology, 1653 West Congress Parkway, 570 Jelke, Chicago, IL 60612, USA.

Adult-onset leukoencephalopathies with increased cerebral volume can present a potentially challenging diagnosis for the pathologist. We present the case of a patient with a rare adult-onset disease called Leukoencephalopathy with cerebral Calcifications and Cysts (LCC). A 55-year-old woman with a history of morning headaches, mild memory loss, diabetes, and hypertension presented to the emergency department with acute onset altered mental status. Read More

Neurology 2017 03;88(12):e113-e114

From the Department of Neurology, San Carlos Institute for Health Research (IdISSC) (R.-N.V.-Q., J.M.-G., J.A.M.-G.), and Department of Radiology (N.G.-R., M.J.-M.), Hospital Clínico San Carlos, Madrid, Spain.

Ann Indian Acad Neurol 2017 Jan-Mar;20(1):59-61

Department of Neurology, St. Stephen's Hospital, New Delhi, India.

Clin Genet 2017 Aug 30;92(2):180-187. Epub 2017 Mar 30.

Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.

Background: Leukoencephalopathy with brain calcifications and cysts (LCC) is neuroradiologically characterized by leukoencephalopathy, intracranial calcification, and cysts. Coats plus syndrome is also characterized by the same neuroradiological findings together with defects in retinal vascular development. Indeed, LCC and Coats plus were originally considered to be the same clinical entity termed cerebroretinal microangiopathy with calcifications and cysts, but evidence suggests that they are genetically distinct. Read More

J Neurol Sci 2017 Feb 11;373:60-65. Epub 2016 Dec 11.

Department of Neurosurgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.

Background: Leukoencephalopathy, cerebral calcifications, and cysts (LCC) is a rare disease that was first reported by Labrune in 1996. A case of adult-onset LCC was successfully followed up for a long period.

Case Presentation: A 30-year-old female presented with visual field disturbance and seizure on several occasions. Read More