RT Journal Article
SR Electronic
T1 Hereditary leukoencephalopathy with axonal spheroids: a spectrum of phenotypes from CNS vasculitis to parkinsonism in an adult onset leukodystrophy series
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP 512
OP 519
DO 10.1136/jnnp-2015-310788
VO 87
IS 5
A1 David S Lynch
A1 Zane Jaunmuktane
A1 Una-Marie Sheerin
A1 Rahul Phadke
A1 Sebastian Brandner
A1 Ionnis Milonas
A1 Andrew Dean
A1 Nin Bajaj
A1 Nuala McNicholas
A1 Daniel Costello
A1 Simon Cronin
A1 Chris McGuigan
A1 Martin Rossor
A1 Nick Fox
A1 Elaine Murphy
A1 Jeremy Chataway
A1 Henry Houlden
YR 2016
UL http://jnnp.bmj.com/content/87/5/512.abstract
AB Background Hereditary diffuse leukoencephalopathy with neuroaxonal spheroids (HDLS) is a hereditary, adult onset leukodystrophy which is characterised by the presence of axonal loss, axonal spheroids and variably present pigmented macrophages on pathological examination. It most frequently presents in adulthood with dementia and personality change. HDLS has recently been found to be caused by mutations in the colony stimulating factor-1 receptor (CSF1R) gene.Methods In this study, we sequenced the CSF1R gene in a cohort of 48 patients from the UK, Greece and Ireland with adult onset leukodystrophy of unknown cause.Results Five pathogenic mutations were found, including three novel mutations. The presentations ranged from suspected central nervous system (CNS) vasculitis to extrapyramidal to cognitive phenotypes. The case histories and imaging are presented here, in addition to neuropathological findings from two cases with novel mutations.Conclusion We estimate that CSF1R mutations account for 10% of idiopathic adult onset leukodystrophies and that genetic testing for CSF1R mutations is essential in adult patients presenting with undefined CNS vasculitis or a leukodystrophy with prominent neuropsychiatric signs or dementia.