Lissencephaly: Expanded imaging and clinical classification

Nataliya Di Donato, Sara Chiari, Ghayda M. Mirzaa, Kimberly A. Aldinger, Elena Parrini, Carissa Olds, A. James Barkovich, Renzo Guerrini, William B. Dobyns

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Lissencephaly (“smooth brain,” LIS) is a malformation of cortical development associated with deficient neuronal migration and abnormal formation of cerebral convolutions or gyri. The LIS spectrum includes agyria, pachygyria, and subcortical band heterotopia. Our first classification of LIS and subcortical band heterotopia (SBH) was developed to distinguish between the first two genetic causes of LIS—LIS1 (PAFAH1B1) and DCX. However, progress in molecular genetics has led to identification of 19 LIS-associated genes, leaving the existing classification system insufficient to distinguish the increasingly diverse patterns of LIS. To address this challenge, we reviewed clinical, imaging and molecular data on 188 patients with LIS-SBH ascertained during the last 5 years, and reviewed selected archival data on another ∼1,400 patients. Using these data plus published reports, we constructed a new imaging based classification system with 21 recognizable patterns that reliably predict the most likely causative genes. These patterns do not correlate consistently with the clinical outcome, leading us to also develop a new scale useful for predicting clinical severity and outcome. Taken together, our work provides new tools that should prove useful for clinical management and genetic counselling of patients with LIS-SBH (imaging and severity based classifications), and guidance for prioritizing and interpreting genetic testing results (imaging based- classification).

Original languageEnglish
Pages (from-to)1473-1488
Number of pages16
JournalAmerican Journal of Medical Genetics, Part A
Volume173
Issue number6
DOIs
Publication statusPublished - Jun 1 2017

Fingerprint

Lissencephaly
Classical Lissencephalies and Subcortical Band Heterotopias
Malformations of Cortical Development
Molecular Imaging
Genetic Counseling
Genetic Testing
Genes
Molecular Biology
Brain

Keywords

  • agyria
  • classification
  • lissencephaly
  • pachygyria
  • subcortical band heterotopia
  • tubulinopathy

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Di Donato, N., Chiari, S., Mirzaa, G. M., Aldinger, K. A., Parrini, E., Olds, C., ... Dobyns, W. B. (2017). Lissencephaly: Expanded imaging and clinical classification. American Journal of Medical Genetics, Part A, 173(6), 1473-1488. https://doi.org/10.1002/ajmg.a.38245

Lissencephaly : Expanded imaging and clinical classification. / Di Donato, Nataliya; Chiari, Sara; Mirzaa, Ghayda M.; Aldinger, Kimberly A.; Parrini, Elena; Olds, Carissa; Barkovich, A. James; Guerrini, Renzo; Dobyns, William B.

In: American Journal of Medical Genetics, Part A, Vol. 173, No. 6, 01.06.2017, p. 1473-1488.

Research output: Contribution to journalArticle

Di Donato, N, Chiari, S, Mirzaa, GM, Aldinger, KA, Parrini, E, Olds, C, Barkovich, AJ, Guerrini, R & Dobyns, WB 2017, 'Lissencephaly: Expanded imaging and clinical classification', American Journal of Medical Genetics, Part A, vol. 173, no. 6, pp. 1473-1488. https://doi.org/10.1002/ajmg.a.38245
Di Donato N, Chiari S, Mirzaa GM, Aldinger KA, Parrini E, Olds C et al. Lissencephaly: Expanded imaging and clinical classification. American Journal of Medical Genetics, Part A. 2017 Jun 1;173(6):1473-1488. https://doi.org/10.1002/ajmg.a.38245
Di Donato, Nataliya ; Chiari, Sara ; Mirzaa, Ghayda M. ; Aldinger, Kimberly A. ; Parrini, Elena ; Olds, Carissa ; Barkovich, A. James ; Guerrini, Renzo ; Dobyns, William B. / Lissencephaly : Expanded imaging and clinical classification. In: American Journal of Medical Genetics, Part A. 2017 ; Vol. 173, No. 6. pp. 1473-1488.
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