18º Congresso Brasileiro de Neurologia Infantil

Dados do Trabalho



Apresentação do caso

ERCT, male, 3 years old, initially followed up by immunology due to recurrent sinopulmonary infections in addition to evidence of hypogammaglobulinemia. Associated with the condition, he started progressive choreo-dystonic movements that proved to be resistant to a drug therapeutic test with levodopa. In a propaedeutic evaluation, analysis of cerebrospinal fluid, electroencephalogram and magnetic resonance imaging of the skull were performed, with results within normal limits. It was decided, then, to carry out a genetic analysis through a panel for movement disorders, which did not show pathogenic genes that would justify the clinical manifestation. In a parallel investigation of immunology, and with the suspicion of combined immunodeficiency, a molecular exome test for immunodeficiencies was performed, which showed a pathogenic variant in hemizygosity of the nonsense type in the CD40LG gene, characterizing the Hyper-IgM Syndrome.


The CD40LG gene, located on chromosome Xq26.3, encodes the ligand for the immune-related molecule CD40. Deficiency of the CD40 ligand has been shown to result in reduced immunoglobulin classes G, A, and E, while IgM levels are normal or elevated. Deficiency of the CD40/CD40L axis deleteriously affects the biological pathways of different cell lineages, manifesting itself as changes in cellular and humoral immunity. It is a pathology transmitted as an X-linked trait and characterized by manifestations in the first years of life through recurrent opportunistic infections involving the respiratory system, gastrointestinal tract, septicemia and autoimmune manifestations. Neurological symptoms are seen in less than 15% of affected patients. Although central nervous system infections are known to occur in cases of CD40L deficiency, with an incidence of around 10% of patients, neurodegeneration is a rare but recognized phenomenon. In the context of CD40L deficiency it is an uncommon association, however described in the literature. All reported cases presented movement disorders with prominent choreic and dystonic elements refractory to drug treatments, as in the case presented here.

Comentários finais

The Hyper IgM Syndrome must be included in the differential diagnosis of choreo-dystonic and dyskinetic presentations that occur associated with immunodeficiencies, as they can evolve with potentially fatal complications and with a significant loss of quality of life with the evolution of neurodegenerative symptoms.

Referências (se houver)

1. Balint B, Mencacci NE, Valente EM, et al. Dystonia. Dystonia Nat Rev Dis Primers. 2018;4(1):25
2. Martinez-Ramirez D, Walker RH, Rodriguez-Violante M, Gatto EM, Rare movement disorders study Group of International Parkinson’s D. Review of hereditary and acquired rare Choreas. Tremor Other Hyperkinet Mov.2020;6(10):24
3. Yildirim M, Ayvaz DC, Konuskan B, et al. Neurologic involvement in primary immunodeficiency disorders. J Child Neurol. 018;33(5):320-328.
4. Škorvánek M, Jech R, Winkelmann J, Zech M. Progressive choreodystonia in X-linked hyper-IgM immunodeficiency: a rare but recurrent presentation. Ann Clin Transl Neurol. 2022 Apr;9(4):577-58. Epub 2022 Mar 10.
5. Coulter IC, Yan H, Gorodetsky C, Akhbari M, Breitbart S, Kalia SK, Fasano A, Ibrahim GM. Childhood choreoathetosis secondary to hyper-IgM syndrome (CD40 ligand deficiency). Neurol Neuroimmunol Neuroinflamm. 2020 Oct 16;7(6):e899.

Palavras Chave

movements disorders; hyper-IgM immunodeficiency syndrome; athetosis; chorea.

Fonte de Fomento (se houver)

Declaração de conflito de interesses de TODOS os autores

Ausência de conflitos de interesses.


Neuroimunologia, esclerose múltipla e outras doenças desmielinizantes


Hospital das Clínicas da Universidade Federal de Pernambuco - Pernambuco - Brasil, Instituto de Medicina Integral Professor Fernando Figueira - IMIP - Pernambuco - Brasil


Andresa Rêgo Barros Vieira Santos, Glidiane Silva Nascimento, Lucas Victor Alves, Paula Teixeira Lyra