Childhood choreoathetosis secondary to hyper-IgM syndrome (CD40 ligand deficiency)

Progressive choreodystonia in X‐linked hyper‐IgM immunodeficiency: a rare but recurrent presentation

“…Notably, the second case was also demonstrated to exhibit clinical response to pallidal deep brain‐stimulation therapy, with significant reduction of abnormal movements after a 6‐month follow‐up 17 . Our patient displayed striking phenotypic overlap with these two previously published cases: he developed signs and symptoms compatible with XHIGM‐related immunodeficiency in early childhood; the manifestation of an intractable hyperkinetic movement disorder affecting the trunk, craniocervical region, and all four limbs followed, although the age of onset was later than in the previously reported subjects (42 vs. 20 years 16 and 13 years, 17 respectively). The movement disorder showed prominent choreatic and dystonic elements, fulfilling clinical diagnostic criteria of a progressive generalized choreodystonic syndrome 2,18,19 .…”

“…In one of the largest XHIGM cohorts assembled to date, 15 seven of 145 patients (5%) were described as having features consistent with nervous‐system involvement such as cognitive impairment, speech disturbances, and ataxic/choreatic movements; a more detailed delineation of the latter association has not been provided in the corresponding publication 15 . A specific relationship between XHIGM and the expression of a hyperkinetic movement disorder has been proposed in two smaller‐scope studies 16,17 . By investigating a group of nine individuals with ataxia telangectasia‐like phenotypes, Hasegawa and colleagues 16 identified a pathogenic truncating CD40LG variant in a single patient who manifested progressive choreoathetosis in addition to an existing immunological defect syndrome with diminished IgG and elevated IgM levels.…”

“…More recently, Coulter and colleagues 17 described an individual with a choreoathetoid generalized movement disorder and hyper‐IgM‐related immunodeficiency who was identified to have a pathogenic single‐exon deletion of CD40LG . Brain MRI scans revealed neurodegenerative changes in both cases, with atrophy of the basal ganglia and the cerebral cortex in the first patient and global supratentorial volume loss in the second 16,17 . Notably, the second case was also demonstrated to exhibit clinical response to pallidal deep brain‐stimulation therapy, with significant reduction of abnormal movements after a 6‐month follow‐up 17 .…”

“…The mechanisms through which CD40LG deleterious variants cause neurodegeneration are incompletely understood 11,17 . Immunodeficiency‐triggered opportunistic infections may be considered one explanation.…”

“…Second, significant information about the nature of disease and the associated complications was obtained, which will be useful for establishing tailored laboratory monitoring and supportive treatment strategies 11 . Finally, deep brain stimulation could emerge as a promising therapeutic intervention in XHIGM‐related movement‐disorder phenotypes 17 …”