Episodic Vestibulocerebellar Ataxia Associated with a CACNA1G Missense Variant

Episodic vestibulocerebellar ataxias are rare diseases, frequently linked to mutations in different ion channels. Our objective in this work was to describe a kindred with episodic vestibular dysfunction and ataxia, associated with a novel CACNA1G variant. Two individuals from successive generations developed episodes of transient dizziness, gait unsteadiness, a sensation of fall triggered by head movements, headache, and cheek numbness. These were suppressed by carbamazepine (CBZ) administration in the proband, although acetazolamide and topiramate worsened instability, and amitriptyline and flunarizine did not prevent headache spells. On examination, the horizontal head impulse test (HIT) yielded saccadic responses bilaterally and was accompanied by cerebellar signs. Two additional family members were asymptomatic, with normal neurological examinations. Reduced vestibulo-ocular reflex gain values, overt and covert saccades were shown by video-assisted HIT in affected subjects. Hearing acuity was normal. Whole-exome sequencing demonstrated the heterozygous CACNA1G missense variant c.6958G>T (p.Gly2320Cys) in symptomatic individuals. It was absent in 1 unaffected member (not tested in the other asymptomatic individual) and should be considered likely pathogenic. CACNA1G encodes for the pore-forming, α1G subunit of the T-type voltage-gated calcium channel (VGCC), in which currents are transient owing to fast inactivation, and tiny, due to small conductance. Mutations in CACNA1G cause generalized absence epilepsy and adult-onset, dominantly inherited, spinocerebellar ataxia type 42. In this kindred, the aforementioned CACNA1G variant segregated with disease, which was consistent with episodic vestibulocerebellar ataxia. CBZ proved successful in bout prevention and provided symptomatic benefit in the proband, probably as a result of interaction of this drug with VGCC. Further studies are needed to fully determine the vestibular and neurological manifestations of this form of episodic vestibulocerebellar ataxia. This novel disease variant could be designated episodic vestibulocerebellar ataxia type 10. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	José Gazulla [verfasserIn] Silvia Izquierdo-Alvarez [verfasserIn] Emilio Ruiz-Fernández [verfasserIn] Alba Lázaro-Romero [verfasserIn] José Berciano [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	vestibular hypofunction cacna1g episodic ataxia type 10 autosomal dominant carbamazepine episodic vestibulocerebellar ataxia type 10 episodic ataxia

Übergeordnetes Werk:	In: Case Reports in Neurology - Karger Publishers, 2009, 13(2021), 2, Seite 347-354
Übergeordnetes Werk:	volume:13 ; year:2021 ; number:2 ; pages:347-354

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1159/000515974

Katalog-ID:	DOAJ053034406

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allfields	10.1159/000515974 doi (DE-627)DOAJ053034406 (DE-599)DOAJ328eb3229eeb4e5ba26f3f73a8e986ef DE-627 ger DE-627 rakwb eng RC346-429 José Gazulla verfasserin aut Episodic Vestibulocerebellar Ataxia Associated with a CACNA1G Missense Variant 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Episodic vestibulocerebellar ataxias are rare diseases, frequently linked to mutations in different ion channels. Our objective in this work was to describe a kindred with episodic vestibular dysfunction and ataxia, associated with a novel CACNA1G variant. Two individuals from successive generations developed episodes of transient dizziness, gait unsteadiness, a sensation of fall triggered by head movements, headache, and cheek numbness. These were suppressed by carbamazepine (CBZ) administration in the proband, although acetazolamide and topiramate worsened instability, and amitriptyline and flunarizine did not prevent headache spells. On examination, the horizontal head impulse test (HIT) yielded saccadic responses bilaterally and was accompanied by cerebellar signs. Two additional family members were asymptomatic, with normal neurological examinations. Reduced vestibulo-ocular reflex gain values, overt and covert saccades were shown by video-assisted HIT in affected subjects. Hearing acuity was normal. Whole-exome sequencing demonstrated the heterozygous CACNA1G missense variant c.6958G>T (p.Gly2320Cys) in symptomatic individuals. It was absent in 1 unaffected member (not tested in the other asymptomatic individual) and should be considered likely pathogenic. CACNA1G encodes for the pore-forming, α1G subunit of the T-type voltage-gated calcium channel (VGCC), in which currents are transient owing to fast inactivation, and tiny, due to small conductance. Mutations in CACNA1G cause generalized absence epilepsy and adult-onset, dominantly inherited, spinocerebellar ataxia type 42. In this kindred, the aforementioned CACNA1G variant segregated with disease, which was consistent with episodic vestibulocerebellar ataxia. CBZ proved successful in bout prevention and provided symptomatic benefit in the proband, probably as a result of interaction of this drug with VGCC. Further studies are needed to fully determine the vestibular and neurological manifestations of this form of episodic vestibulocerebellar ataxia. This novel disease variant could be designated episodic vestibulocerebellar ataxia type 10. vestibular hypofunction cacna1g episodic ataxia type 10 autosomal dominant carbamazepine episodic vestibulocerebellar ataxia type 10 episodic ataxia Neurology. Diseases of the nervous system Silvia Izquierdo-Alvarez verfasserin aut Emilio Ruiz-Fernández verfasserin aut Alba Lázaro-Romero verfasserin aut José Berciano verfasserin aut In Case Reports in Neurology Karger Publishers, 2009 13(2021), 2, Seite 347-354 (DE-627)605212678 (DE-600)2505302-4 1662680X nnns volume:13 year:2021 number:2 pages:347-354 https://doi.org/10.1159/000515974 kostenfrei https://doaj.org/article/328eb3229eeb4e5ba26f3f73a8e986ef kostenfrei https://www.karger.com/Article/FullText/515974 kostenfrei https://doaj.org/toc/1662-680X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2018 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2021 2 347-354
spelling	10.1159/000515974 doi (DE-627)DOAJ053034406 (DE-599)DOAJ328eb3229eeb4e5ba26f3f73a8e986ef DE-627 ger DE-627 rakwb eng RC346-429 José Gazulla verfasserin aut Episodic Vestibulocerebellar Ataxia Associated with a CACNA1G Missense Variant 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Episodic vestibulocerebellar ataxias are rare diseases, frequently linked to mutations in different ion channels. Our objective in this work was to describe a kindred with episodic vestibular dysfunction and ataxia, associated with a novel CACNA1G variant. Two individuals from successive generations developed episodes of transient dizziness, gait unsteadiness, a sensation of fall triggered by head movements, headache, and cheek numbness. These were suppressed by carbamazepine (CBZ) administration in the proband, although acetazolamide and topiramate worsened instability, and amitriptyline and flunarizine did not prevent headache spells. On examination, the horizontal head impulse test (HIT) yielded saccadic responses bilaterally and was accompanied by cerebellar signs. Two additional family members were asymptomatic, with normal neurological examinations. Reduced vestibulo-ocular reflex gain values, overt and covert saccades were shown by video-assisted HIT in affected subjects. Hearing acuity was normal. Whole-exome sequencing demonstrated the heterozygous CACNA1G missense variant c.6958G>T (p.Gly2320Cys) in symptomatic individuals. It was absent in 1 unaffected member (not tested in the other asymptomatic individual) and should be considered likely pathogenic. CACNA1G encodes for the pore-forming, α1G subunit of the T-type voltage-gated calcium channel (VGCC), in which currents are transient owing to fast inactivation, and tiny, due to small conductance. Mutations in CACNA1G cause generalized absence epilepsy and adult-onset, dominantly inherited, spinocerebellar ataxia type 42. In this kindred, the aforementioned CACNA1G variant segregated with disease, which was consistent with episodic vestibulocerebellar ataxia. CBZ proved successful in bout prevention and provided symptomatic benefit in the proband, probably as a result of interaction of this drug with VGCC. Further studies are needed to fully determine the vestibular and neurological manifestations of this form of episodic vestibulocerebellar ataxia. This novel disease variant could be designated episodic vestibulocerebellar ataxia type 10. vestibular hypofunction cacna1g episodic ataxia type 10 autosomal dominant carbamazepine episodic vestibulocerebellar ataxia type 10 episodic ataxia Neurology. Diseases of the nervous system Silvia Izquierdo-Alvarez verfasserin aut Emilio Ruiz-Fernández verfasserin aut Alba Lázaro-Romero verfasserin aut José Berciano verfasserin aut In Case Reports in Neurology Karger Publishers, 2009 13(2021), 2, Seite 347-354 (DE-627)605212678 (DE-600)2505302-4 1662680X nnns volume:13 year:2021 number:2 pages:347-354 https://doi.org/10.1159/000515974 kostenfrei https://doaj.org/article/328eb3229eeb4e5ba26f3f73a8e986ef kostenfrei https://www.karger.com/Article/FullText/515974 kostenfrei https://doaj.org/toc/1662-680X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2018 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2021 2 347-354
allfields_unstemmed	10.1159/000515974 doi (DE-627)DOAJ053034406 (DE-599)DOAJ328eb3229eeb4e5ba26f3f73a8e986ef DE-627 ger DE-627 rakwb eng RC346-429 José Gazulla verfasserin aut Episodic Vestibulocerebellar Ataxia Associated with a CACNA1G Missense Variant 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Episodic vestibulocerebellar ataxias are rare diseases, frequently linked to mutations in different ion channels. Our objective in this work was to describe a kindred with episodic vestibular dysfunction and ataxia, associated with a novel CACNA1G variant. Two individuals from successive generations developed episodes of transient dizziness, gait unsteadiness, a sensation of fall triggered by head movements, headache, and cheek numbness. These were suppressed by carbamazepine (CBZ) administration in the proband, although acetazolamide and topiramate worsened instability, and amitriptyline and flunarizine did not prevent headache spells. On examination, the horizontal head impulse test (HIT) yielded saccadic responses bilaterally and was accompanied by cerebellar signs. Two additional family members were asymptomatic, with normal neurological examinations. Reduced vestibulo-ocular reflex gain values, overt and covert saccades were shown by video-assisted HIT in affected subjects. Hearing acuity was normal. Whole-exome sequencing demonstrated the heterozygous CACNA1G missense variant c.6958G>T (p.Gly2320Cys) in symptomatic individuals. It was absent in 1 unaffected member (not tested in the other asymptomatic individual) and should be considered likely pathogenic. CACNA1G encodes for the pore-forming, α1G subunit of the T-type voltage-gated calcium channel (VGCC), in which currents are transient owing to fast inactivation, and tiny, due to small conductance. Mutations in CACNA1G cause generalized absence epilepsy and adult-onset, dominantly inherited, spinocerebellar ataxia type 42. In this kindred, the aforementioned CACNA1G variant segregated with disease, which was consistent with episodic vestibulocerebellar ataxia. CBZ proved successful in bout prevention and provided symptomatic benefit in the proband, probably as a result of interaction of this drug with VGCC. Further studies are needed to fully determine the vestibular and neurological manifestations of this form of episodic vestibulocerebellar ataxia. This novel disease variant could be designated episodic vestibulocerebellar ataxia type 10. vestibular hypofunction cacna1g episodic ataxia type 10 autosomal dominant carbamazepine episodic vestibulocerebellar ataxia type 10 episodic ataxia Neurology. Diseases of the nervous system Silvia Izquierdo-Alvarez verfasserin aut Emilio Ruiz-Fernández verfasserin aut Alba Lázaro-Romero verfasserin aut José Berciano verfasserin aut In Case Reports in Neurology Karger Publishers, 2009 13(2021), 2, Seite 347-354 (DE-627)605212678 (DE-600)2505302-4 1662680X nnns volume:13 year:2021 number:2 pages:347-354 https://doi.org/10.1159/000515974 kostenfrei https://doaj.org/article/328eb3229eeb4e5ba26f3f73a8e986ef kostenfrei https://www.karger.com/Article/FullText/515974 kostenfrei https://doaj.org/toc/1662-680X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2018 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2021 2 347-354
allfieldsGer	10.1159/000515974 doi (DE-627)DOAJ053034406 (DE-599)DOAJ328eb3229eeb4e5ba26f3f73a8e986ef DE-627 ger DE-627 rakwb eng RC346-429 José Gazulla verfasserin aut Episodic Vestibulocerebellar Ataxia Associated with a CACNA1G Missense Variant 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Episodic vestibulocerebellar ataxias are rare diseases, frequently linked to mutations in different ion channels. Our objective in this work was to describe a kindred with episodic vestibular dysfunction and ataxia, associated with a novel CACNA1G variant. Two individuals from successive generations developed episodes of transient dizziness, gait unsteadiness, a sensation of fall triggered by head movements, headache, and cheek numbness. These were suppressed by carbamazepine (CBZ) administration in the proband, although acetazolamide and topiramate worsened instability, and amitriptyline and flunarizine did not prevent headache spells. On examination, the horizontal head impulse test (HIT) yielded saccadic responses bilaterally and was accompanied by cerebellar signs. Two additional family members were asymptomatic, with normal neurological examinations. Reduced vestibulo-ocular reflex gain values, overt and covert saccades were shown by video-assisted HIT in affected subjects. Hearing acuity was normal. Whole-exome sequencing demonstrated the heterozygous CACNA1G missense variant c.6958G>T (p.Gly2320Cys) in symptomatic individuals. It was absent in 1 unaffected member (not tested in the other asymptomatic individual) and should be considered likely pathogenic. CACNA1G encodes for the pore-forming, α1G subunit of the T-type voltage-gated calcium channel (VGCC), in which currents are transient owing to fast inactivation, and tiny, due to small conductance. Mutations in CACNA1G cause generalized absence epilepsy and adult-onset, dominantly inherited, spinocerebellar ataxia type 42. In this kindred, the aforementioned CACNA1G variant segregated with disease, which was consistent with episodic vestibulocerebellar ataxia. CBZ proved successful in bout prevention and provided symptomatic benefit in the proband, probably as a result of interaction of this drug with VGCC. Further studies are needed to fully determine the vestibular and neurological manifestations of this form of episodic vestibulocerebellar ataxia. This novel disease variant could be designated episodic vestibulocerebellar ataxia type 10. vestibular hypofunction cacna1g episodic ataxia type 10 autosomal dominant carbamazepine episodic vestibulocerebellar ataxia type 10 episodic ataxia Neurology. Diseases of the nervous system Silvia Izquierdo-Alvarez verfasserin aut Emilio Ruiz-Fernández verfasserin aut Alba Lázaro-Romero verfasserin aut José Berciano verfasserin aut In Case Reports in Neurology Karger Publishers, 2009 13(2021), 2, Seite 347-354 (DE-627)605212678 (DE-600)2505302-4 1662680X nnns volume:13 year:2021 number:2 pages:347-354 https://doi.org/10.1159/000515974 kostenfrei https://doaj.org/article/328eb3229eeb4e5ba26f3f73a8e986ef kostenfrei https://www.karger.com/Article/FullText/515974 kostenfrei https://doaj.org/toc/1662-680X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2018 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2021 2 347-354
allfieldsSound	10.1159/000515974 doi (DE-627)DOAJ053034406 (DE-599)DOAJ328eb3229eeb4e5ba26f3f73a8e986ef DE-627 ger DE-627 rakwb eng RC346-429 José Gazulla verfasserin aut Episodic Vestibulocerebellar Ataxia Associated with a CACNA1G Missense Variant 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Episodic vestibulocerebellar ataxias are rare diseases, frequently linked to mutations in different ion channels. Our objective in this work was to describe a kindred with episodic vestibular dysfunction and ataxia, associated with a novel CACNA1G variant. Two individuals from successive generations developed episodes of transient dizziness, gait unsteadiness, a sensation of fall triggered by head movements, headache, and cheek numbness. These were suppressed by carbamazepine (CBZ) administration in the proband, although acetazolamide and topiramate worsened instability, and amitriptyline and flunarizine did not prevent headache spells. On examination, the horizontal head impulse test (HIT) yielded saccadic responses bilaterally and was accompanied by cerebellar signs. Two additional family members were asymptomatic, with normal neurological examinations. Reduced vestibulo-ocular reflex gain values, overt and covert saccades were shown by video-assisted HIT in affected subjects. Hearing acuity was normal. Whole-exome sequencing demonstrated the heterozygous CACNA1G missense variant c.6958G>T (p.Gly2320Cys) in symptomatic individuals. It was absent in 1 unaffected member (not tested in the other asymptomatic individual) and should be considered likely pathogenic. CACNA1G encodes for the pore-forming, α1G subunit of the T-type voltage-gated calcium channel (VGCC), in which currents are transient owing to fast inactivation, and tiny, due to small conductance. Mutations in CACNA1G cause generalized absence epilepsy and adult-onset, dominantly inherited, spinocerebellar ataxia type 42. In this kindred, the aforementioned CACNA1G variant segregated with disease, which was consistent with episodic vestibulocerebellar ataxia. CBZ proved successful in bout prevention and provided symptomatic benefit in the proband, probably as a result of interaction of this drug with VGCC. Further studies are needed to fully determine the vestibular and neurological manifestations of this form of episodic vestibulocerebellar ataxia. This novel disease variant could be designated episodic vestibulocerebellar ataxia type 10. vestibular hypofunction cacna1g episodic ataxia type 10 autosomal dominant carbamazepine episodic vestibulocerebellar ataxia type 10 episodic ataxia Neurology. Diseases of the nervous system Silvia Izquierdo-Alvarez verfasserin aut Emilio Ruiz-Fernández verfasserin aut Alba Lázaro-Romero verfasserin aut José Berciano verfasserin aut In Case Reports in Neurology Karger Publishers, 2009 13(2021), 2, Seite 347-354 (DE-627)605212678 (DE-600)2505302-4 1662680X nnns volume:13 year:2021 number:2 pages:347-354 https://doi.org/10.1159/000515974 kostenfrei https://doaj.org/article/328eb3229eeb4e5ba26f3f73a8e986ef kostenfrei https://www.karger.com/Article/FullText/515974 kostenfrei https://doaj.org/toc/1662-680X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2018 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2021 2 347-354
language	English
source	In Case Reports in Neurology 13(2021), 2, Seite 347-354 volume:13 year:2021 number:2 pages:347-354
sourceStr	In Case Reports in Neurology 13(2021), 2, Seite 347-354 volume:13 year:2021 number:2 pages:347-354
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	vestibular hypofunction cacna1g episodic ataxia type 10 autosomal dominant carbamazepine episodic vestibulocerebellar ataxia type 10 episodic ataxia Neurology. Diseases of the nervous system
isfreeaccess_bool	true
container_title	Case Reports in Neurology
authorswithroles_txt_mv	José Gazulla @@aut@@ Silvia Izquierdo-Alvarez @@aut@@ Emilio Ruiz-Fernández @@aut@@ Alba Lázaro-Romero @@aut@@ José Berciano @@aut@@
publishDateDaySort_date	2021-01-01T00:00:00Z
hierarchy_top_id	605212678
id	DOAJ053034406
language_de	englisch
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callnumber-first	R - Medicine
author	José Gazulla
spellingShingle	José Gazulla misc RC346-429 misc vestibular hypofunction misc cacna1g misc episodic ataxia type 10 misc autosomal dominant misc carbamazepine misc episodic vestibulocerebellar ataxia type 10 misc episodic ataxia misc Neurology. Diseases of the nervous system Episodic Vestibulocerebellar Ataxia Associated with a CACNA1G Missense Variant
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topic_title	RC346-429 Episodic Vestibulocerebellar Ataxia Associated with a CACNA1G Missense Variant vestibular hypofunction cacna1g episodic ataxia type 10 autosomal dominant carbamazepine episodic vestibulocerebellar ataxia type 10 episodic ataxia
topic	misc RC346-429 misc vestibular hypofunction misc cacna1g misc episodic ataxia type 10 misc autosomal dominant misc carbamazepine misc episodic vestibulocerebellar ataxia type 10 misc episodic ataxia misc Neurology. Diseases of the nervous system
topic_unstemmed	misc RC346-429 misc vestibular hypofunction misc cacna1g misc episodic ataxia type 10 misc autosomal dominant misc carbamazepine misc episodic vestibulocerebellar ataxia type 10 misc episodic ataxia misc Neurology. Diseases of the nervous system
topic_browse	misc RC346-429 misc vestibular hypofunction misc cacna1g misc episodic ataxia type 10 misc autosomal dominant misc carbamazepine misc episodic vestibulocerebellar ataxia type 10 misc episodic ataxia misc Neurology. Diseases of the nervous system
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title	Episodic Vestibulocerebellar Ataxia Associated with a CACNA1G Missense Variant
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title_full	Episodic Vestibulocerebellar Ataxia Associated with a CACNA1G Missense Variant
author_sort	José Gazulla
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author_browse	José Gazulla Silvia Izquierdo-Alvarez Emilio Ruiz-Fernández Alba Lázaro-Romero José Berciano
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author-letter	José Gazulla
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title_sort	episodic vestibulocerebellar ataxia associated with a cacna1g missense variant
callnumber	RC346-429
title_auth	Episodic Vestibulocerebellar Ataxia Associated with a CACNA1G Missense Variant
abstract	Episodic vestibulocerebellar ataxias are rare diseases, frequently linked to mutations in different ion channels. Our objective in this work was to describe a kindred with episodic vestibular dysfunction and ataxia, associated with a novel CACNA1G variant. Two individuals from successive generations developed episodes of transient dizziness, gait unsteadiness, a sensation of fall triggered by head movements, headache, and cheek numbness. These were suppressed by carbamazepine (CBZ) administration in the proband, although acetazolamide and topiramate worsened instability, and amitriptyline and flunarizine did not prevent headache spells. On examination, the horizontal head impulse test (HIT) yielded saccadic responses bilaterally and was accompanied by cerebellar signs. Two additional family members were asymptomatic, with normal neurological examinations. Reduced vestibulo-ocular reflex gain values, overt and covert saccades were shown by video-assisted HIT in affected subjects. Hearing acuity was normal. Whole-exome sequencing demonstrated the heterozygous CACNA1G missense variant c.6958G>T (p.Gly2320Cys) in symptomatic individuals. It was absent in 1 unaffected member (not tested in the other asymptomatic individual) and should be considered likely pathogenic. CACNA1G encodes for the pore-forming, α1G subunit of the T-type voltage-gated calcium channel (VGCC), in which currents are transient owing to fast inactivation, and tiny, due to small conductance. Mutations in CACNA1G cause generalized absence epilepsy and adult-onset, dominantly inherited, spinocerebellar ataxia type 42. In this kindred, the aforementioned CACNA1G variant segregated with disease, which was consistent with episodic vestibulocerebellar ataxia. CBZ proved successful in bout prevention and provided symptomatic benefit in the proband, probably as a result of interaction of this drug with VGCC. Further studies are needed to fully determine the vestibular and neurological manifestations of this form of episodic vestibulocerebellar ataxia. This novel disease variant could be designated episodic vestibulocerebellar ataxia type 10.
abstractGer	Episodic vestibulocerebellar ataxias are rare diseases, frequently linked to mutations in different ion channels. Our objective in this work was to describe a kindred with episodic vestibular dysfunction and ataxia, associated with a novel CACNA1G variant. Two individuals from successive generations developed episodes of transient dizziness, gait unsteadiness, a sensation of fall triggered by head movements, headache, and cheek numbness. These were suppressed by carbamazepine (CBZ) administration in the proband, although acetazolamide and topiramate worsened instability, and amitriptyline and flunarizine did not prevent headache spells. On examination, the horizontal head impulse test (HIT) yielded saccadic responses bilaterally and was accompanied by cerebellar signs. Two additional family members were asymptomatic, with normal neurological examinations. Reduced vestibulo-ocular reflex gain values, overt and covert saccades were shown by video-assisted HIT in affected subjects. Hearing acuity was normal. Whole-exome sequencing demonstrated the heterozygous CACNA1G missense variant c.6958G>T (p.Gly2320Cys) in symptomatic individuals. It was absent in 1 unaffected member (not tested in the other asymptomatic individual) and should be considered likely pathogenic. CACNA1G encodes for the pore-forming, α1G subunit of the T-type voltage-gated calcium channel (VGCC), in which currents are transient owing to fast inactivation, and tiny, due to small conductance. Mutations in CACNA1G cause generalized absence epilepsy and adult-onset, dominantly inherited, spinocerebellar ataxia type 42. In this kindred, the aforementioned CACNA1G variant segregated with disease, which was consistent with episodic vestibulocerebellar ataxia. CBZ proved successful in bout prevention and provided symptomatic benefit in the proband, probably as a result of interaction of this drug with VGCC. Further studies are needed to fully determine the vestibular and neurological manifestations of this form of episodic vestibulocerebellar ataxia. This novel disease variant could be designated episodic vestibulocerebellar ataxia type 10.
abstract_unstemmed	Episodic vestibulocerebellar ataxias are rare diseases, frequently linked to mutations in different ion channels. Our objective in this work was to describe a kindred with episodic vestibular dysfunction and ataxia, associated with a novel CACNA1G variant. Two individuals from successive generations developed episodes of transient dizziness, gait unsteadiness, a sensation of fall triggered by head movements, headache, and cheek numbness. These were suppressed by carbamazepine (CBZ) administration in the proband, although acetazolamide and topiramate worsened instability, and amitriptyline and flunarizine did not prevent headache spells. On examination, the horizontal head impulse test (HIT) yielded saccadic responses bilaterally and was accompanied by cerebellar signs. Two additional family members were asymptomatic, with normal neurological examinations. Reduced vestibulo-ocular reflex gain values, overt and covert saccades were shown by video-assisted HIT in affected subjects. Hearing acuity was normal. Whole-exome sequencing demonstrated the heterozygous CACNA1G missense variant c.6958G>T (p.Gly2320Cys) in symptomatic individuals. It was absent in 1 unaffected member (not tested in the other asymptomatic individual) and should be considered likely pathogenic. CACNA1G encodes for the pore-forming, α1G subunit of the T-type voltage-gated calcium channel (VGCC), in which currents are transient owing to fast inactivation, and tiny, due to small conductance. Mutations in CACNA1G cause generalized absence epilepsy and adult-onset, dominantly inherited, spinocerebellar ataxia type 42. In this kindred, the aforementioned CACNA1G variant segregated with disease, which was consistent with episodic vestibulocerebellar ataxia. CBZ proved successful in bout prevention and provided symptomatic benefit in the proband, probably as a result of interaction of this drug with VGCC. Further studies are needed to fully determine the vestibular and neurological manifestations of this form of episodic vestibulocerebellar ataxia. This novel disease variant could be designated episodic vestibulocerebellar ataxia type 10.
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title_short	Episodic Vestibulocerebellar Ataxia Associated with a CACNA1G Missense Variant
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score	7.3998127

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Episodic Vestibulocerebellar Ataxia Associated with a CACNA1G Missense Variant

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Vorhandene Bände

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