Expanding the Spectrum of Stress-Induced Childhood-Onset Neurodegeneration with Variable Ataxia and Seizures (CONDSIAS)
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
|---|---|
| Enthalten in: |
Cerebellum (London, England) - 23(2024), 2 vom: 30. März, Seite 861-871 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Lindskov, Filippa Orlien [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
ADPRS |
|---|
| Anmerkungen: |
Date Completed 20.03.2024 Date Revised 20.03.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1007/s12311-023-01582-w |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM358935717 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM358935717 | ||
| 003 | DE-627 | ||
| 005 | 20240320233236.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1007/s12311-023-01582-w |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1337.xml |
| 035 | |a (DE-627)NLM358935717 | ||
| 035 | |a (NLM)37392332 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Lindskov, Filippa Orlien |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Expanding the Spectrum of Stress-Induced Childhood-Onset Neurodegeneration with Variable Ataxia and Seizures (CONDSIAS) |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 20.03.2024 | ||
| 500 | |a Date Revised 20.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Case Reports | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a ADPRS | |
| 650 | 4 | |a ARH3 | |
| 650 | 4 | |a Ataxia | |
| 650 | 4 | |a Autosomal recessive | |
| 650 | 4 | |a CONDSIAS | |
| 650 | 4 | |a Cerebellar ataxia | |
| 650 | 7 | |a Poly(ADP-ribose) Polymerase Inhibitors |2 NLM | |
| 700 | 1 | |a Karlsson, William Kristian |e verfasserin |4 aut | |
| 700 | 1 | |a Skovbølling, Sara Lyngby |e verfasserin |4 aut | |
| 700 | 1 | |a Nielsen, Emilie Neerup |e verfasserin |4 aut | |
| 700 | 1 | |a Dunø, Morten |e verfasserin |4 aut | |
| 700 | 1 | |a Stokholm, Jette |e verfasserin |4 aut | |
| 700 | 1 | |a Henriksen, Otto Mølby |e verfasserin |4 aut | |
| 700 | 1 | |a Langkilde, Annika Reynberg |e verfasserin |4 aut | |
| 700 | 1 | |a Nielsen, Jørgen Erik |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cerebellum (London, England) |d 2002 |g 23(2024), 2 vom: 30. März, Seite 861-871 |w (DE-627)NLM126368899 |x 1473-4230 |7 nnns |
| 773 | 1 | 8 | |g volume:23 |g year:2024 |g number:2 |g day:30 |g month:03 |g pages:861-871 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1007/s12311-023-01582-w |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 23 |j 2024 |e 2 |b 30 |c 03 |h 861-871 | ||