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

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

doi:10.1186/s12883-021-02531-y

Cited by 9 publications

(6 citation statements)

References 37 publications

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“…The primary pathological change seems to be an occlusive small cerebrovascular disease. Chronic ischemic necrosis of brain tissue leads to dystrophic calcification, which eventually forms cysts and leukoencephalopathy (Kleinschmidt‐Demasters et al, 2009 ; Nagae‐Poetscher et al, 2004 ; Paff et al, 2022 ). Therefore, the two diseases could be considered hereditary cerebral small vessel diseases (HCSVD).…”

Section: Discussionmentioning

confidence: 99%

Complex cerebrovascular diseases in Roberts syndrome caused by novel biallelic ESCO2 variations

Chen

et al. 2023

Molec Gen & Gen Med

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Objective Roberts syndrome (RBS), also known as Roberts‐SC phocomelia syndrome, is a rare autosomal recessive developmental disorder caused by mutations in the ESCO2 gene. Cardinal clinical manifestations are pre‐ and postnatal growth retardation and craniofacial and limb malformations. Here, we report RBS in a Chinese adolescent with novel biallelic ESCO2 variations and complex cerebrovascular diseases. Methods Medical history, neurological examinations, neuroimaging, and pathology were collected in the proband and the family. Whole exome sequencing (WES) with copy number variation analysis was performed to screen for genetic variations. Results The clinical features of the proband were craniofacial and limb malformations together with complex cerebrovascular diseases. She suffered ischemic stroke at 6 years old and died of cerebellar hemorrhage secondary to an aneurysm at 13 years old. Besides, neuroimaging showed the triad of leukoencephalopathy, calcifications, and cysts. Brain histopathology revealed angiomatous changes and perivascular cysts suggesting chronic small cerebral vasculopathy. Whole exome sequencing (WES) identified novel biallelic variations in the ESCO2 gene (c.1220A>T, p.H407L and c.1562delC, p.A521fs). Conclusions We describe complex cerebrovascular diseases in Roberts syndrome caused by novel ESCO2 biallelic variations. This case expands not only the cerebral involvement in Roberts syndrome but also the disease spectrum of the neuroimaging triad with leukoencephalopathy, calcifications, and cysts.

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Section: Discussionmentioning

confidence: 99%

Complex cerebrovascular diseases in Roberts syndrome caused by novel biallelic ESCO2 variations

Chen

et al. 2023

Molec Gen & Gen Med

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“…The age at which symptoms appear varies greatly, and symptom onset as late as age 70 has been described, though most affected individuals manifest with some symptoms by adolescence or early adulthood. Clinical manifestations are seizures, progressive pyramidal, extrapyramidal, cerebellar signs, increased intracranial pressure, ischemic, and hemorrhagic strokes ( 87 , 88 ). Acute or subacute worsening due to hemorrhage and mass effect due to enlargement of cysts can occur rarely, warranting surgical intervention ( 88 ).…”

Section: Imaging Presentations: Difference From Childhood Leukodystro...mentioning

confidence: 99%

Adult-onset leukodystrophies: a practical guide, recent treatment updates, and future directions

Muthusamy¹,

Sivadasan²,

Dixon³

et al. 2023

Front. Neurol.

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Adult-onset leukodystrophies though individually rare are not uncommon. This group includes several disorders with isolated adult presentations, as well as several childhood leukodystrophies with attenuated phenotypes that present at a later age. Misdiagnoses often occur due to the clinical and radiological overlap with common acquired disorders such as infectious, immune, inflammatory, vascular, metabolic, and toxic etiologies. Increased prevalence of non-specific white matter changes in adult population poses challenges during diagnostic considerations. Clinico-radiological spectrum and molecular landscape of adult-onset leukodystrophies have not been completely elucidated at this time. Diagnostic approach is less well-standardized when compared to the childhood counterpart. Absence of family history and reduced penetrance in certain disorders frequently create a dilemma. Comprehensive evaluation and molecular confirmation when available helps in prognostication, early initiation of treatment in certain disorders, enrollment in clinical trials, and provides valuable information for the family for reproductive counseling. In this review article, we aimed to formulate an approach to adult-onset leukodystrophies that will be useful in routine practice, discuss common adult-onset leukodystrophies with usual and unusual presentations, neuroimaging findings, recent advances in treatment, acquired mimics, and provide an algorithm for comprehensive clinical, radiological, and genetic evaluation that will facilitate early diagnosis and consider active treatment options when available. A high index of suspicion, awareness of the clinico-radiological presentations, and comprehensive genetic evaluation are paramount because treatment options are available for several disorders when diagnosed early in the disease course.

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“…Leukoencephalopathy with calcifications and cysts (LCC), first described by P. Labrune in 1996 (Labrune syndrome), is an extremely rare disease caused by biallelic mutations in the SNORD118 gene, with more than 100 recorded cases worldwide [1-3]. The disease is characterized by the neuroradiological triad of oedematous leukoencephalopathy, cerebral calcifications, and parenchymal cyst formation [4].…”

Section: Figurementioning

confidence: 99%

Leukoencephalopathy with calcifications and cysts: a case study with long‐term follow‐up

Lomidze¹,

Chutkerashvili²,

Tskhvaradze

et al. 2022

Epileptic Disorders

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

Cited by 9 publications

References 37 publications

Complex cerebrovascular diseases in Roberts syndrome caused by novel biallelic ESCO2 variations

Complex cerebrovascular diseases in Roberts syndrome caused by novel biallelic ESCO2 variations

Adult-onset leukodystrophies: a practical guide, recent treatment updates, and future directions

Leukoencephalopathy with calcifications and cysts: a case study with long‐term follow‐up

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