Expanding the Spectrum of Stress-Induced Childhood-Onset Neurodegeneration with Variable Ataxia and Seizures (CONDSIAS).

Autor: Lindskov FO; Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.; Neurogenetics Clinic & Research Lab, Danish Dementia Research Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark., Karlsson WK; Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. wkarlsson@dadlnet.dk., Skovbølling SL; Department of Neurology, Copenhagen University Hospital, Bispebjerg Hospital, Copenhagen, Denmark., Nielsen EN; Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark., Dunø M; Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark., Stokholm J; Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark., Henriksen OM; Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark., Langkilde AR; Department of Radiology, Diagnostic Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark., Nielsen JE; Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.; Neurogenetics Clinic & Research Lab, Danish Dementia Research Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Jazyk: angličtina
Zdroj: Cerebellum (London, England) [Cerebellum] 2024 Apr; Vol. 23 (2), pp. 861-871. Date of Electronic Publication: 2023 Jul 01.
DOI: 10.1007/s12311-023-01582-w
Abstrakt: Stress-induced childhood-onset neurodegeneration with variable ataxia and seizures (CONDSIAS) is an extremely rare, autosomal recessive neurodegenerative disorder. It is caused by biallelic pathogenic variants in the ADPRS gene, which encodes an enzyme involved in DNA repair, and is characterized by exacerbations in relation to physical or emotional stress, and febrile illness. We report a 24-year-old female, who was compound heterozygous for two novel pathogenic variants revealed by whole exome sequencing. Additionally, we summarize the published cases of CONDSIAS. In our patient, onset of symptoms occurred at 5 years of age and consisted of episodes of truncal dystonic posturing, followed half a year later by sudden diplopia, dizziness, ataxia, and gait instability. Progressive hearing loss, urinary urgency, and thoracic kyphoscoliosis ensued. Present neurological examination revealed dysarthria, facial mini-myoclonus, muscle weakness and atrophy of hands and feet, leg spasticity with clonus, truncal and appendicular ataxia, and spastic-ataxic gait. Hybrid [18F]-fluorodeoxyglucose (FDG) positron emission tomography/magnetic resonance imaging (PET/MRI) of the brain revealed cerebellar atrophy, particularly of the vermis, with corresponding hypometabolism. MRI of the spinal cord showed mild atrophy. After informed consent from the patient, we initiated experimental, off-label treatment with minocycline, a poly-ADP-polymerase (PARP) inhibitor, which has shown beneficial effects in a Drosophila fly model. The present case report expands the list of known pathogenic variants in CONDIAS and presents details of the clinical phenotype. Future studies will reveal whether PARP inhibition is an effective treatment strategy for CONDIAS.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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