Abstract 11- 1445-1500
At the end of the session,
participants will be able to:
- Cite the most common etiologies of HPE.
- Appreciate the occurrence and origin of aberrant white mater tracts in HPE.
- Discuss the preferred location and etiology of ischemic-like white matter damage in HPE.
Dr. Christopher Dunham was born and raised in Edmonton, Alberta, Canada, Dr. Chris Dunham received his B.Sc. in Science Psychology at the University of Alberta (1996) after which he obtained his MD from the University of Ottawa in 2001. His interest in Neuropathology was peaked by an early mentor, Dr. Vital Montpetit, Neuropathologist at Ottawa General Hospital. After medical school, Dr. Dunham completed his residency training in Neuropathology at the University of Calgary. Upon graduation in 2006, Dr. Dunham spent a year of fellowship training in Molecular Neuropathology under the guidance of Dr. Arie Perry at Washington University in St. Louis, MO, USA. After a summer locum at the University of Saskatchewan in 2007, Dr. Dunham joined the Department of Pathology and Laboratory Medicine, Division of Anatomical Pathology, at BC Children’s Hospital in October of 2007. Dr. Dunham was Program Director of the UBC Neuropathology Residency Training Program from 2010-2014 and was Head of the Division of Anatomical Pathology from 2013-2017. He is a full time Neuropathologist with interest in all areas of neuropathology including neuro-oncology and developmental neuropathology.
Sumit Das1, Jessica Saunders2, Sarah Nikkel3, Lindsay Brown4, Christopher Dunham2
1Department of Pathology and Lab Medicine, University Hospital, Edmonton
2Division of Anatomical Pathology, BC Children’s Hospital
3Department of Medical Genetics, BC Children’s Hospital
4Division of Genome Diagnostics, BC Children’s Hospital
Pathologists, Residents, Medical Students
Medical Expert (the integrating role), Communicator, Collaborator, Scholar, Professional
Ischemic-like pathology in aberrant white matter tracts of fetal holoprosencephaly: a case series.
Holoprosencephaly (HPE) is due to defective early forebrain induction resulting in a “lack of cleavage” of the primitive prosencephalon into paired cerebral hemispheres. HPE is generally considered sporadic, although clear environmental and genetic factors have been recognized. From a genetic perspective, an autosomal dominant inheritance pattern is most commonly noted. Chromosomal abnormalities are common in HPE, seen in 25-50% of affected individuals, with Trisomy 13 being the most frequent. A number of structural chromosomal abnormalities (e.g., 21q22.3 deletion) and pathogenic copy number variations have also been described, as have syndromic associations. Pertinent biologic pathways include SHH, NODAL and BMP; in turn, several single gene mutations related to these pathways have been uncovered, including SHH, ZIC2, and SIX3. Although not frequently emphasized in neuropathologic descriptions of HPE, abnormal white matter has been reported, mainly in the form of aberrant tracts (e.g., absence of the corpus callosum and hypoplasia of the corticospinal pathway). In this study, we detail the clinicopathologic features of 8 fetal BCCH cases bearing a seemingly unique dual form of white pathology. All 8 cases demonstrated ischemic-like pathology, with 7 of 8 exhibiting such pathology in a similar location – ventral to the fused deep grey nuclei. Diffusion tensor imaging (DTI) studies suggest that the neuroanatomic substrate of this aberrant white matter is fused superior and inferior occipito-frontal fasciculi, with the resultant fibers crossing the midline. While the etiology of this ischemic-like pathology is unclear, the literature raises the possibility of a role for the SHH pathway.