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. 2026 Sep 28;12(13):CASE26650. doi: 10.3171/CASE26650

The first reported case of Labrune syndrome in Vietnam with 4-year longitudinal follow-up: illustrative case

Duy Pham 1,2, Hung Manh Ngo 1,2,✉, Quang Dung Doan 3, Duc Thuong Ho 4, Son Tung Tran 1,2, Mai Phuong Nguyen 5, Trong Hiep Nguyen 1
PMCID: PMC13618014  PMID: 42804799

Abstract

BACKGROUND

Labrune syndrome, also known as leukoencephalopathy with cerebral calcifications and cysts (LCC), is a rare autosomal recessive cerebral microangiopathy. Because of its rarity and microangiopathic pathology of recurrent cysts, no curative treatment is available, which makes long-term management challenging for clinicians.

OBSERVATIONS

A 34-year-old woman born to consanguineous parents presented in 2022 with chronic headache and blurred vision. Imaging revealed diffuse leukoencephalopathy, intracranial calcifications, and multiple parenchymal cysts, with a dominant left hemispheric lesion causing mass effect. She underwent left-sided cyst decompression with good symptomatic relief, followed-up by imaging surveillance. Three years later, she developed recurrent headache and worsening vision. Imaging demonstrated enlargement of a right-sided cyst with significant midline shift. Right-sided decompression surgery again improved her symptoms. Histopathological specimens from both surgeries showed no neoplasia; additionally, the second specimen demonstrated gliosis and hyalinized microvasculature. Subsequent genetic testing identified a novel homozygous SNORD118 variant, supporting the LCC diagnosis.

LESSONS

This case highlights that LCC diagnosis is supported by radiological findings, pathological features, and SNORD118 genetic findings. Additionally, long-term follow-up is essential due to metachronous enlargement of cysts, and repeat decompressions could provide symptomatic relief.

https://thejns.org/doi/10.3171/CASE26650

Keywords: Labrune syndrome, leukoencephalopathy, cyst, calcification, case report

ABBREVIATIONS: ICP = intracranial pressure, LCC = leukoencephalopathy with cerebral calcifications and cysts, TSE = turbo spin echo, WGS = whole-genome sequencing

Labrune syndrome is a rare inherited disorder of the CNS that is caused by autosomal mutations in the SNORD118 gene.1 It is characterized by a radiological triad consisting of diffuse leukoencephalopathy, intracranial calcifications, and parenchymal brain cysts.2 Since its first description in 1996, fewer than 100 cases have been reported worldwide.2–5

Clinically, Labrune syndrome, also known as leukoencephalopathy with cerebral calcifications and cysts (LCC), often presents with varied and nonspecific neurological signs. Symptoms include headache, seizures, cognitive impairment, and focal neurological deficits. They are frequently related to cyst enlargement or increased intracranial pressure (ICP).6 Neuroimaging plays a crucial role in diagnosis, with MRI demonstrating diffuse white matter abnormalities and parenchymal cysts, and CT revealing bilateral intracranial calcifications.2,7 Management of Labrune syndrome remains challenging because no curative therapy is currently available.5 Surgical intervention is primarily indicated for symptomatic cysts to relieve mass effect and increased ICP.5 However, cyst recurrence is common because of the underlying cerebral microangiopathy, and therefore repeated surgical procedures may be required.8

We herein report the first surgically treated case of Labrune syndrome in Vietnam, involving an adult patient with recurrent symptomatic parenchymal brain cysts. The patient underwent operations for separated cysts in opposite hemispheres. We describe the clinical course, imaging characteristics, surgical management, and follow-up and highlight practical implications for diagnosis and long-term care.

Illustrative Case

A 34-year-old woman of San Chay ethnicity, an ethnic minority group in Vietnam, presented with a history of intermittent headache. The patient was born to consanguineous parents (within three generations). She had no significant past medical history and no known family history of neurological disorders.

The patient was first admitted in August 2022 with progressively worsening headache and blurred vision. She denied seizures, limb weakness, or sensory disturbances. Neurological examination revealed no focal motor deficits. Ophthalmological examination demonstrated bilateral blurred optic disc margins consistent with early papilledema, with mildly reduced visual acuity. No other clinically apparent extra-neurological manifestations were identified. Brain MRI performed at the initial admission confirmed numerous parenchymal cysts of variable size (Fig. 1A). The largest cyst was located in the left hemisphere (Fig. 1A–C), causing mass effect with midline shift. The cysts were hypointense on T1-weighted images without contrast enhancement (Fig. 1A) and hyperintense on T2-weighted turbo spin echo (TSE) images (Fig. 1C). T2*-weighted imaging revealed marked blooming artifacts corresponding to parenchymal calcification (Fig. 1B). Routine laboratory tests, including complete blood count, inflammatory markers, metabolic panel, parasitic screening, and infectious workup, were within normal limits. Based on the significant mass effect from the left-sided cyst, surgical decompression was indicated. Intraoperatively, there was no clear dissection plane between the cyst wall and the surrounding brain parenchyma. Frozen-section examination demonstrated only reactive gliotic brain tissue without evidence of neoplasia. Therefore, to minimize the risk of neurological injury, we left the cyst wall in place.

FIG. 1.

FIG. 1.

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Neuroimaging and intraoperative findings. A–C: Preoperative images obtained at the first admission before the first surgery in 2022, demonstrating the characteristic radiological features of LCC. A: Axial postcontrast T1-weighted MR image showing multiple bilateral parenchymal cysts without contrast enhancement (arrowheads), including a dominant left hemispheric cyst (asterisk). B: Axial T2*-weighted MR image showing blooming artifacts within the bilateral white matter, suggestive of parenchymal calcifications (arrowheads). The asterisk indicates the left hemispheric cyst. C: Coronal T2-weighted TSE image showing a large left-sided hyperintense cyst (asterisk) causing midline shift. D–F: Preoperative images obtained before the second surgery in 2025, demonstrating progressive enlargement of a contralateral cyst. D: Axial postcontrast T1-weighted MR image showing an enlarged right hemispheric cyst (asterisk) without contrast enhancement. E: Axial FLAIR image demonstrating diffuse periventricular and deep white matter hyperintensity, consistent with leukoencephalopathy (arrowheads) surrounding the enlarged right-sided cyst (asterisk). F: Axial noncontrast CT scan demonstrating extensive intracranial calcifications involving the basal ganglia (arrowheads) and a large hypodense right hemispheric cyst (asterisk) causing mass effect. Intraoperative findings during the second surgery. G: Thin cyst wall encountered after corticectomy, adherent to the surrounding brain parenchyma without a clear dissection plane. H: Xanthochromic cyst fluid (arrow). I: Microhemorrhages in the cyst cavity (arrow).

Following the first surgery in 2022, the patient experienced marked improvement in headache and partial recovery of vision. She was subsequently followed up regularly at 1 month, 3 months, 6 months, and annually. MRI demonstrated stable postoperative changes in the left hemisphere but interval development and gradual enlargement of a cyst in the right hemisphere. In November 2025, the patient returned with progressive headache and visual decline over 1 month. Neurological examination again revealed no motor deficits. Ophthalmological evaluation showed papilledema. MRI demonstrated significant enlargement of the right hemispheric cyst, causing mass effect and midline shift (Fig. 1D–F). The patient therefore underwent right-sided cyst decompression. Intraoperatively, the cyst walls were thin but firmly adherent to the surrounding brain parenchyma, with evidence of abnormal, fragile microvasculature (Fig. 1G and I). The cyst fluid appeared xanthochromic (suggestive of hemoglobin degradation) and was collected for laboratory analysis (Fig. 1H). No solid tumor component was identified.

Histopathological examination performed after the first surgery in 2022 revealed no evidence of neoplasia. Tissue obtained in the second surgery demonstrated hyalinized small vessels with dystrophic calcifications embedded within gliotic brain tissue (Fig. 2A). Reactive gliosis with scattered microcalcifications was also observed (Fig. 2B). No evidence of neoplasia, granulomatous inflammation, or signs of parasitic infection was observed. Analysis of the cyst fluid revealed elevated protein (38.0 g/L), a glucose level of 3.89 mmol/L, and low cellularity with minimal red blood cells.

FIG. 2.

FIG. 2.

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Histopathological findings from the cyst wall specimen. A: H&E stain (original magnification ×40) demonstrating hyalinized small vessels with prominent calcifications (arrow) within gliotic brain tissue. B: H&E stain (original magnification ×200) demonstrating scattered microcalcifications (arrow) within reactive glial tissue.

Given the radiological triad and the absence of neoplastic, infectious, or inflammatory evidence on histopathological findings, several diagnoses were suspected, including Labrune syndrome and Coats plus syndrome. Genetic testing was therefore indicated for the patient. A novel homozygous SNORD118 variant was identified, which was subsequently confirmed by Sanger sequencing (Fig. 3).

FIG. 3.

FIG. 3.

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Sanger sequencing confirmed the homozygous SNORD118 variant NR_033294.2:n.31C>G, which was initially identified by WGS. The chromatogram is shown in the reverse-strand orientation and demonstrates a single nucleotide peak at the variant position, consistent with homozygosity. The arrow indicates the mutation site.

The postoperative course after both surgeries was favorable. Headache improved substantially and visual symptoms lessened. Additionally, no new neurological deficits occurred. MRI confirmed adequate decompression with relief of mass effect. At the most recent follow-up, the patient remained clinically and radiologically stable (Fig. 4). Long-term clinical and radiological surveillance was planned.

FIG. 4.

FIG. 4.

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Longitudinal observation with contrast-enhanced axial (A), sagittal (B), and coronal (C) T1-weighted MR images from 2022 to 2026. Serial imaging demonstrates stability of the left-sided cyst following the first surgery in 2022 (red asterisk). A new right hemispheric cyst became evident in 2024 and showed progressive enlargement through 2025 (yellow asterisk). After the second surgical decompression in 2025, both cysts remained stable on 2026 follow-up imaging.

Informed Consent

The necessary informed consent was obtained in this study.

Discussion

Observations

This report describes a 34-year-old woman who was followed longitudinally for 4 years after initial cyst decompressive surgery in 2022. At presentation, MRI showed multiple intracranial cysts, calcifications, and leukoencephalopathy (Figs. 1 and 4), although LCC was not initially suspected because of its rarity. During follow-up, the patient required another decompressive surgery for enlargement of a contralateral cyst. Histopathological sampling of cyst wall from both surgeries demonstrated nonneoplastic features, while the second specimen demonstrated gliosis, hyalinized microvasculature, and calcifications consistent with an underlying microangiopathic process (Fig. 2). Subsequent genetic testing identified a novel homozygous SNORD118 variant (Fig. 3). All of these findings supported the diagnosis of LCC. Surgical management was directed toward relief of mass effect rather than cure of the disease process. To our knowledge, 13 genetically confirmed LCC cases that required surgical intervention have been reported in the literature (Table 1).

TABLE 1.

Reported SNORD118 mutation–confirmed cases of LCC requiring surgical intervention

Authors & Year Age (yrs)/Sex SNORD118 Variant(s) Surgical Intervention Outcome/Follow-Up
Shtaya et al., 201925 12/M n.72A>G; n.*10G>T Endoscopic cerebellar cyst aspiration & Ommaya reservoir placement Symptomatic improvement
Osman et al., 20206 11–12/F (patient 3) n.72A>G; n.92C>T Multiple cyst resections (6 procedures) Recurrent hemorrhage & cyst enlargement
Kobets et al., 202124 16/F SNORD118 mutation Stereotactic aspiration & Ommaya reservoir Improved hemiparesis
Osman et al., 20206 18/F (patient 4) n.72A>G; n.39_40insT Repeated cyst aspiration/resection (3 procedures) Recurrent cyst formation
Guan et al., 202628 22/M n.3C>T; n.74G>A Bilat frontal cyst resection & lat parietal cyst resection Recurrent cyst formation
Pessoa, 201829 24/M n.*1C>T; n.61A>G Cyst resection & cyst ventricular shunt Clinical stabilization
Novegno et al., 20245 24/M n.3C>T; n.20C>T 2 craniotomies for cyst aspiration & endoscopic cyst fenestration w/ Ommaya reservoir Recurrent cyst formation
Wilson et al., 202430 26/F n.-6G>A; n.131C>G Ommaya reservoir later converted to Rickham reservoir Reservoir obstruction
Osman et al., 20206 28/F (patient 2) n.74G>T; n.*9C>T Repeated cyst aspiration (5 procedures) Recurrent cyst enlargement
Cullinane et al., 202031 32/F Homozygous n.*5C>G Multiple craniotomies & ventriculoperitoneal shunt Recurrent cyst formation
Paff et al., 202232 36/F n.*9C>T; n.59T>C Stereotactic white matter biopsy Diagnosis established
Wang et al., 202233 53/M n.3C>T; n.24C>T Ommaya reservoir placement Decompression of large frontal cyst
Osman et al., 20206 60/F (patient 5) n.131C>T; n.*9C>T Repeated cerebellar cyst resection (2 procedures) Recurrent cyst formation
Present case 34/F Homozygous NR_033294.2:n.31C>G (VUS) Lt cyst decompression (2022) & contralat cyst decompression (2025) Stable after 2nd surgery w/ 4-yr follow-up
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VUS = variant of uncertain significance.

First, neuroimaging plays a crucial role in establishing the diagnosis of Labrune syndrome, particularly when genetic testing is unavailable. The LCC characteristic triad includes intracranial calcifications, diffuse leukoencephalopathy, and parenchymal cysts.2 Calcifications can be detected on CT and typically involve the basal ganglia, thalami, and dentate nuclei, while T2*-weighted MRI sequences may demonstrate corresponding blooming.3,5,9–12 MRI also reveals bilateral T2/FLAIR hyperintensity signals within the periventricular and deep white matter, with relative preservation of the corpus callosum, which helps distinguish Labrune syndrome from primary demyelinating conditions.8,11–13 Parenchymal cysts may occur in both supratentorial and infratentorial locations, show rim enhancement, and enlarge progressively.5,9,12,14 Increasing cyst volume may result in mass effect, which is the main indication for decompressive surgery.

Second, the progressive enlargement of parenchymal cysts in Labrune syndrome is considered to primarily result from diffuse cerebral microangiopathy.2 Chronic vascular occlusion causes progressive ischemic injury of the brain parenchyma, leading to the formation and gradual coalescence of multiple microcysts into larger cystic lesions.13,15,16 In addition, blood-brain barrier disruption with increased vascular permeability may contribute to progressive cyst enlargement through continuous leakage of protein-rich fluid into the brain parenchyma.8,17,18 Recurrent microhemorrhages from fragile vessels, with angiogenesis and increased vascular permeability, may further drive progressive cyst enlargement.5,14,19 Together, these mechanisms explain the progressive cyst growth in Labrune syndrome.

Third, genetic testing has become an important tool for confirming the diagnosis of LCC since it rules out Coats plus syndrome caused by CTC1 gene mutation or other phenotypically similar disorders. In our case, whole-genome sequencing (WGS) identified a novel homozygous SNORD118 variant, NR_033294.2:n.31C>G, which was validated by Sanger sequencing (Fig. 3). According to the American College of Medical Genetics and Genomics and Association for Molecular Pathology ClinGen Sequence Variant Interpretation guidelines, the variant is currently classified as a variant of uncertain significance (which met PM2, PP4, and PM3 supporting criteria).20,21 The n.31C>G variant is located within the mature U8 snoRNA sequence, a functionally important region in which pathogenic variants have been shown to impair U8 maturation, stability, or function, resulting in defective ribosome assembly and cerebral microangiopathy.22,23 Although the clinical phenotype and neuroimaging findings in our patient are highly consistent with LCC, the contribution of this novel variant to the disease remains uncertain. Nevertheless, its absence from population databases, homozygous occurrence in an individual with clinical features compatible with LCC, and location within a functionally important region of SNORD118 suggest that it represents a plausible candidate variant. This report expands the spectrum of reported SNORD118 variants and provides additional evidence for future variant interpretation. Further functional studies and familial segregation analysis will be necessary to clarify the pathogenicity and clinical significance of this variant.

From a therapeutic perspective, surgery remains the main symptomatic management in Labrune syndrome, particularly when enlarging parenchymal cysts cause mass effect or neurological decline.5 The main objective is relief of compression rather than cure of the underlying microangiopathy.5,24 Various strategies have been described, ranging from stereotactic aspiration, Ommaya reservoir placement, and neuroendoscopy to open procedures.5,24,25 These strategies strongly depend on cyst location, accessibility, and local resources. In our patient, craniotomy with cyst decompression improved the patient’s headache and visual symptoms on both occasions. However, surgical treatment has several limitations. Because of the underlying microangiopathy, cysts frequently recur or new lesions may develop at different sites (Fig. 4), which could lead to several surgeries during follow-up. Radical excision of the cyst wall is usually avoided, as it is often adherent to surrounding parenchyma and contains fragile abnormal vessels that increase the risk of hemorrhage (Fig. 1I) and permanent deficit. Consequently, surgeries are mostly palliative. These challenges highlight the need for radiological surveillance and individualized decision-making.

Lastly, long-term surveillance is a critical component of care in Labrune syndrome because of the progressive and unpredictable microangiopathy and high recurrence rate.5 Serial imaging commonly demonstrates gradual expansion of calcifications and white matter abnormalities, while parenchymal cysts may enlarge or newly appear during follow-up.8,26 Importantly, cyst size can change gradually, and neurological deterioration might occur once mass effect or increased ICP develops.4,5,27 Therefore, regular follow-up allows clinicians to recognize the transition from a stable stage to an active phase that needs intervention. Furthermore, monitoring is particularly essential after surgery, as recurrence or formation of new cysts is around 50% in several weeks to 2 years.5 Early radiological detection allows treatment to be timed before severe complications arise.5,27 It helps guide individualized decisions regarding repeat decompression versus continued observation.

Lessons

In Labrune syndrome, radiological findings, pathological features, and SNORD118 genetic findings are important for establishing the diagnosis. Cysts are the main cause of clinical deterioration when mass effect develops. Surgical decompression can provide symptomatic relief, but it does not halt the underlying progressive microangiopathy that drives continued cyst enlargement. Therefore, timely recognition of mass effect and long-term neuroimaging surveillance are essential for optimal management.

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author Contributions

Conception and design: Ngo, Pham, Doan, TH Nguyen. Acquisition of data: all authors. Analysis and interpretation of data: Ngo, Pham, Doan, Ho, MP Nguyen, TH Nguyen. Drafting the article: Ngo, Pham, Doan, Ho, MP Nguyen, TH Nguyen. Critically revising the article: Ngo, Pham, Ho, Tran, TH Nguyen. Reviewed submitted version of manuscript: Ngo, Pham, Doan, Tran, MP Nguyen, TH Nguyen. Approved the final version of the manuscript on behalf of all authors: Ngo. Statistical analysis: Pham, Ho, MP Nguyen, TH Nguyen. Administrative/technical/material support: Ngo, Pham, Doan, TH Nguyen. Study supervision: Ngo, Pham.

Correspondence

Hung Manh Ngo: Faculty of Medicine, University of Medicine and Pharmacy, Vietnam National University, Cau Giay, Hanoi, Vietnam. ngomanhhung2000@gmail.com.

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