A familial case of Congenital Mirror Movement (CMM) Syndrome Associated With A Novel DCC Variant
Ankur Nayyar1, Marie Davis2, Swati Levendovsky3
1Neurology, VA Puget Sound Health Care System, Seattle, WA, 2Neurology, University of Washington Dept of Neurology, 3Radiology, University of Washington Dept of Radiology
Objective:
Presenting a case of a three-generation family with CMM.
Background:
Mirror movements can be observed in neurodegenerative disorders, characterized by involuntary movements of one side of the body that mirror intentional movements on opposite side. Congenital mirror movements (CMM) is manifested by early-onset of these mirror movements in individuals without clinical signs or symptoms. Heterozygous pathologic variants in DCC, NTN1, RAD51, and DNAL4 have been associated with CMM and abnormalities or agenesis of the corpus callosum and concomitant cognitive and/or neuropsychiatric issues. The underlying molecular mechanisms causing CMM are hypothesized to be due to aberrant axonal projections and disrupted netrin1 signaling, particularly in commissural neurons.
Design/Methods:
Whole exome sequencing was performed on the proband (Prevention Genetics). Based on prior studies showing callosal abnormalities in individuals with CMM, an MRI brain was obtained. Additional imaging studies, including tractography of the callosal fibers and functional connectivity across bilateral cortical regions will be obtained and compared to age- and gender-matched individuals.
Results:
48-year-old male presented with a lifelong history of abnormal movements, described as unwanted movements of one side of his body when performing the same exact voluntary movements contralaterally. No other abnormal neurological findings or cognitive complaints on exam. Same symptoms are present in patient’s father and son but not his brother. Clinical whole exome sequencing revealed a variant of uncertain significance in the gene DCC c.4009 C>T (p.Arg1337*) in the proband. This nonsense variant near the C-terminal in DCC netrin 1 receptor predicted to be pathogenic and not yet been reported. Clinical MRI brain was unremarkable and did not reveal corpus callosum abnormalities.
Conclusions:
A three-generation family with CMM likely due to a novel DCC variant. Subsequent segregation analysis of this variant in the son, father, and unaffected brother are pending. Functional imaging studies are being conducted to understand the underlying neurophysiology of CMM.