Systemic involvement in adult‐onset leukoencephalopathy with intracranial calcifications and cysts (Labrune syndrome) with a novel mutation of the SNORD118 gene

Abstract

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. Amplification of the SNORD118 gene and Sanger sequencing were integrated to investigate potential causative mutations. Results: A 69-year-old woman, with a long history of episodes of vertigo and gait imbalance, was referred to our hospital for progressive cognitive and motor deterioration. Computed tomography and magnetic resonance imaging disclosed diffuse bilateral leukoencephalopathy in periventricular and deep white matter, widespread calcifications and numerous cysts in the brain, liver, pancreas and kidneys. The genetic analysis revealed two biallelic variants in the SNORD118 gene, one of which is novel (n.60G>C). Conclusions: This is the first report of adult-onset Labrune syndrome with an unusual systemic involvement presenting a novel mutation in the SNORD118 gene.

Paediatric neurosurgical implications of a ribosomopathy: illustrative case and literature review

“…A 69-year-old woman began to show symptoms at age 37 and demonstrated diffuse bilateral leukoencephalopathy on MRI [6]. A gradual decline in both cognition and motor ability occurred over the next 32 years [6]. In another patient, MRI scans at the age of six showed bilateral cysts in the cerebral hemispheres.…”

“…The cysts exert mass effect and are directly related to the neurological manifestations of the disease [24]. LCC is restricted to the central nervous system; extra- N/A AEDs helped relieve symptoms neurologic manifestations have only been described in three patients, with two having café au lait spots and a third demonstrating cysts in the liver, kidney and pancreas [6,29]. A related condition, Coats syndrome, is also caused by a microangiopathy; in addition to the cerebral changes, patients with Coats syndrome also have retinal angiopathy, causing bleeding and exudative retinopathy [29].…”

“…These symptoms may present suddenly or at a slow, insidious rate. A 69-year-old woman began to show symptoms at age 37 and demonstrated diffuse bilateral leukoencephalopathy on MRI [6]. A gradual decline in both cognition and motor ability occurred over the next 32 years [6].…”

Case report: Moderate therapeutic response to Bevacizumab in late-onset Labrune syndrome

“…Labrune syndrome is caused by the mutation of the SNORD118 gene encoding the box C/D snoRNA U8, first described by Labrune et al ( 1 , 2 ). LS was presented with wide neurological dysfunctions like progressive cognitive impairments, gait disturbance, and seizures but on rare occasions, LS might have systemic involvements such as multiple hepatic and renal cysts ( 4 ). Our patient presented with seizures, cognitive impairments, and right hemiparesis.…”

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

“…Neuroimaging features commonly described include diffuse bilateral cerebral white matter T2 hyperintensity, particularly surrounding cysts [21]. Relative sparing of the corpus callosum and subcortical U-fibres has been reported while the posterior fossa white matter is variably affected [22,23]. Cerebral calcifications are commonly asymmetrically scattered within the cerebral white matter or deep gray nuclei, rarely in the cerebellum, either as small punctate foci or larger confluent areas [11].…”