MRI characteristics due to gene mutations in a Chinese pedigree with Lafora disease

Abstract

Background and PurposeLafora disease (LD) is a very rare autosomal recessive disorder manifesting primarily as fatal, congenital, and neurodegenerative epilepsies. We aimed to describe the MRI characteristics due to gene mutations in a Chinese pedigree with LD.MethodsWhole‐exome sequencing, muscle biopsy, pedigree analysis, and MRI analysis were conducted. Five family members (two of whom were affected by LD) were whole‐genome sequenced. Longitudinal changes in brain MRI volumes were analyzed by Freesurfer.ResultsWe identified a new intron heterozygous mutation in the EMP2A gene c.71 (exon 1) G>A in a Chinese LD pedigree that was characterized by refractory seizures, progressive vision impairment, and declines in motor and cognitive functions. The patient suffered generalized tonic–clonic seizures since the age of 15 years and had severe forms of progressive myoclonic seizure. She eventually died after being admitted to the intensive care unit due to status epilepticus at the age of 24 years. Period acid Schiff staining showed positive polyglucosan particles in muscle biopsy specimens. Regions of atrophy in the whole brain, and especially in the hippocampus, were detected.ConclusionsWe identified a new heterozygous mutation (c.71+1G>A) in a Chinese LD pedigree, which broadens the mutation spectrum of LD genes. We found that the patient exhibited brain volumetric atrophy along with rapidly worsening symptoms. These results contribute to our understanding of LD.

Progressive Myoclonus Epilepsy: A Scoping Review of Diagnostic, Phenotypic and Therapeutic Advances

“…Several studies have looked for imaging and electroretinogram (ERG) abnormalities that could either serve as biomarkers or, at the very least, shorten the duration of the diagnostic process for patients and their families. A case report from China identified a patient with LD who was found to have non-specific global brain atrophy on MRI at the time of diagnosis [48]. This finding differs from a 2006 cohort imaging study of patients with LD, which identified minimal MRI brain volume changes but significant MRS changes in frontal cortex and basal ganglia [49].…”

Lafora Disease: A Case Report and Evolving Treatment Advancements

“…When histological features are described, (i) they refer to skin biopsy [25] or (ii) authors do not specify the analyzed tissue [39]. A single study described the muscle biopsy of a LD patient harboring a homozygous EPM2A mutation [40]: histological analysis highlighted uneven muscle fiber dimensions, with most of the fibers showing considerable sarcoplasmic vacuolization; whilePAS staining identified the presence of PAS-positive polyglucosan aggregates.…”