Cobblestone malformation in LAMA2 congenital muscular dystrophy (MDC1A)

Himali Jayakody, Sanam Zarei, Huy Nguyen, Joline Dalton, Kelly Chen, Louanne Hudgins, John Day, Kara Withrow, Arti Pandya, Jean Teasley, William B. Dobyns, Katherine D. Mathews, Steven A. Moore

Research output: Contribution to journalArticlepeer-review

Abstract

Congenital muscular dystrophy type 1A (MDC1A) is caused by recessive variants in laminin α2(LAMA2). Patients have been found to have white matter signal abnormalities on magnetic resonance imaging (MRI) but rarely structural brain abnormalities. We describe the autopsy neuropathology in a 17-year-old with white matter signal abnormalities on brain MRI. Dystrophic pathology was observed in skeletal muscle, and the sural nerve manifested a mild degree of segmental demyelination and remyelination. A diffuse, bilateral cobblestone appearance, and numerous points of fusion between adjacent gyri were apparent on gross examination of the cerebrum. Brain histopathology included focal disruptions of the glia limitans associated with abnormal cerebral cortical lamination or arrested cerebellar granule cell migration. Subcortical nodular heterotopia was present within the cerebellar hemispheres. Sampling of the centrum semiovale revealed no light microscopic evidence of leukoencephalopathy. Three additional MDC1A patients were diagnosed with cobblestone malformation on brain MRI. Unlike the autopsied patient whose brain had a symmetric distribution of cobblestone pathology, the latter patients had asymmetric involvement, most severe in the occipital lobes. These cases demonstrate that cobblestone malformation may be an important manifestation of the brain pathology in MDC1A and can be present even when patients have a structurally normal brain MRI.

Original languageEnglish (US)
Pages (from-to)998-1010
Number of pages13
JournalJournal of neuropathology and experimental neurology
Volume79
Issue number9
DOIs
StatePublished - 2021
Externally publishedYes

Bibliographical note

Funding Information:
This study was funded by the Iowa Wellstone Muscular Dystrophy Coopera-tive Research Center, NINDS (U54-NS053672 to K.D.M. and S.A.M.).

Publisher Copyright:
© 2020 Oxford University Press. All rights reserved.

Keywords

  • Cobblestone malformation
  • MDC1A
  • Merosin deficiency
  • Neuropathology

PubMed: MeSH publication types

  • Case Reports
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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