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

• Published in: Annals of clinical and translational neurology Vol. 9; no. 4; pp. 577 - 581
• Main Authors: Škorvánek, Matej, Jech, Robert, Winkelmann, Juliane, Zech, Michael
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2022; John Wiley & Sons, Inc; Wiley
• Subjects: Adult; Age; Ataxia; Atrophy; Case Study; CD40 Ligand - genetics; Child; Dyskinesia; Humans; Hyper-IgM Immunodeficiency Syndrome, Type 1 - genetics; Hyper-IgM Immunodeficiency Syndrome, Type 1 - pathology; Immune system; Immunoglobulins; Immunology; Infections; Ligands; Magnetic resonance imaging; Male; Movement disorders; Mutation; Neurodegeneration; Patients; Psychotropic drugs
• ISSN: 2328-9503; 2328-9503
• DOI: 10.1002/acn3.51538

An association between movement disorders and immune‐system dysfunction has been described in the context of rare genetic diseases such as ataxia telangiectasia as well as infectious encephalopathies. We encountered a male patient who presented immunodeficiency of unknown etiology since childhood. A medication‐refractory, progressive choreodystonic movement disorder emerged at the age of 42 years and prompted an exome‐wide molecular testing approach. This revealed a pathogenic hemizygous variant in CD40LG, the gene implicated in X‐linked hyper‐IgM syndrome. Only two prior reports have specifically suggested a causal relationship between CD40LG mutations and involuntary hyperkinetic movements. Our findings thus confirm the existence of a particular CD40LG‐related condition, combining features of compromised immunity with neurodegenerative movement abnormalities. Establishing the diagnosis is crucial because of potential life‐threatening immunological complications.