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Labrune Syndrome

Summary

  • Rare genetic disorder characterised by leukoencephalopathy, brain calcifications, and cysts
  • Caused by mutations in the SNORD118 gene, affecting small nucleolar RNA function
  • Typically presents in childhood with neurological symptoms and progressive course1

Pathophysiology

  • Autosomal recessive inheritance pattern
  • Mutations in SNORD118 gene, encoding U8 small nucleolar RNA
  • Disruption of ribosomal RNA processing and protein synthesis
  • Leads to white matter abnormalities, calcifications, and cyst formation in the brain
  • Exact mechanism of cyst formation remains unclear

Demographics

  • Rare disorder with fewer than 50 cases reported worldwide
  • No clear gender predilection
  • Typically presents in childhood, but adult-onset cases have been described
  • Most reported cases are from consanguineous families

Diagnosis

  • Clinical presentation:
    • Developmental delay or regression
    • Seizures
    • Ataxia
    • Spasticity
    • Cognitive decline
  • Genetic testing:
    • Identification of biallelic mutations in SNORD118 gene
  • Neuroimaging findings (see Imaging section)
  • Exclusion of other leukoencephalopathies and calcifying disorders

Imaging

  • Computed Tomography (CT):
    • Bilateral calcifications in basal ganglia, thalami, and subcortical white matter
    • Hypodense cystic lesions
  • Magnetic Resonance Imaging (MRI):
    • T2-weighted and FLAIR hyperintensities in cerebral white matter
    • Cystic lesions with variable signal intensity
    • Calcifications appear as hypointense foci on T2* or susceptibility-weighted imaging
  • MR Spectroscopy:
    • Reduced N-acetylaspartate (NAA) peak
    • Elevated choline and lactate peaks in affected white matter

panels-1

  • A 30-year-old patient with known diagnosis of Labrune syndrome had a surveillance scan after surgery to drain a cyst (not shown).
  • MRI showed a diffuse leukoencephalopathy with microcalcification and punctate enhancement.

Treatment

  • The triad of leukoencephalopathy, brain calcifications and cysts (LCC) is the hallmark; management is supportive, with surgery to decompress enlarging cysts

Differential diagnosis

Differential Diagnosis Differentiating Feature
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) Absence of calcifications on brain imaging
Coats plus syndrome Presence of retinal telangiectasias and exudates
Aicardi-Goutières syndrome Earlier onset, typically in infancy
Primary familial brain calcification (Fahr's disease) Lack of white matter abnormalities
Cerebroretinal microangiopathy with calcifications and cysts (CRMCC) Presence of retinal vascular abnormalities
Mitochondrial encephalopathy Typically associated with other systemic manifestations
Multiple sclerosis Absence of calcifications and cysts on brain imaging
Cerebral amyloid angiopathy Typically affects older adults, lacks cysts
Cerebral vasculitis Absence of calcifications, different pattern of white matter changes
Leukoencephalopathy with calcifications and cysts (LCC) Considered the same entity as Labrune syndrome by some researchers

  1. Kobets et al. Surgical considerations in Labrune syndrome. 2021. Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery - Open in new tab. ↩