J Pediatr Neurol
DOI: 10.1055/s-0039-1684016
Case Report
Georg Thieme Verlag KG Stuttgart · New York

Neuropathologic Findings in a Child with a Novel Variant of TBCK-Related Encephaloneuronopathy

Sonja Chen
1  Department of Pathology and Laboratory Medicine, Rhode Island Hospital, Providence Rhode Island, United States
6  The Alpert Medical School of Brown University, Providence Rhode Island, United States
,
Fouad Zakka
1  Department of Pathology and Laboratory Medicine, Rhode Island Hospital, Providence Rhode Island, United States
6  The Alpert Medical School of Brown University, Providence Rhode Island, United States
,
Salwa Khedr
1  Department of Pathology and Laboratory Medicine, Rhode Island Hospital, Providence Rhode Island, United States
4  Department of Pathology and Laboratory Medicine, Women and Infants Hospital of Rhode Island, Providence Rhode Island, United States
6  The Alpert Medical School of Brown University, Providence Rhode Island, United States
,
Shamlal Mangray
1  Department of Pathology and Laboratory Medicine, Rhode Island Hospital, Providence Rhode Island, United States
6  The Alpert Medical School of Brown University, Providence Rhode Island, United States
,
Lauren Massingham
2  Departments of Pathology and Laboratory Medicine and Genetics, Rhode Island Hospital, Providence Rhode Island, United States
6  The Alpert Medical School of Brown University, Providence Rhode Island, United States
,
1  Department of Pathology and Laboratory Medicine, Rhode Island Hospital, Providence Rhode Island, United States
3  Departments of Neurology, Neurosurgery and Medicine, Rhode Island Hospital, Providence Rhode Island, United States
4  Department of Pathology and Laboratory Medicine, Women and Infants Hospital of Rhode Island, Providence Rhode Island, United States
5  Department of Pathology and Laboratory Medicine, The Providence VA Medical Center, Providence Rhode Island, United States
6  The Alpert Medical School of Brown University, Providence Rhode Island, United States
› Author Affiliations
Further Information

Publication History

10 January 2019

27 February 2019

Publication Date:
24 April 2019 (eFirst)

Abstract

A 3-year-old girl with developmental delays, hypotonia, and generalized seizures was diagnosed with a novel variant of a heterozygous mutation in the TBC1 domain containing kinase (TBCK) gene. Postmortem findings revealed severe hypotrophy of cerebral white matter, hypogenesis of the corpus callosum with reduced myelination and oligodendrocyte populations, and reactive gliosis, and venous angiomas of the cerebrum, brainstem, and cerebellum white matter. This report is the first to link a TBCK gene mutation to impaired white matter development with the targeting of central nervous system myelin and oligodendrocytes. The mechanism may involve inhibition of signaling through (mTORC1).