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Case report
Alternating Hemiplegia of Childhood and Neurological Comorbidities. Variable Intrafamilial Clinical Features.
Piero Pavone
University of Catania
Corresponding Author
ORCiD: https://orcid.org/0000-0002-5600-9560
License:
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BACKGROUND Alternating Hemiplegia of Childhood (AHC) is an uncommon and complex disorder characterized by age of onset before 18 months, recurrent hemiplegia of one or either sides of the body or quadriplegia. Developmental delay, epilepsy, tonic or dystonic spells, nystagmus and autonomic manifestations are frequently reported manifestations. AHC is mainly caused by mutations in ATP1A3 gene, and to a lesser extent in ATP1A2 gene.
CASE PRESENTATION Clinical and genetic findings of a couple of twins and a couple of siblings affected by AHC from two different Italian families were deeply examined. Intrafamilial clinical variability was shown in the present cases. A pathogenic variant rs606231437 in ATP1A3 gene was detected in twins, while in one of the siblings was found a novel variant of GRIN2A (c.3175T>A) gene, shared by the other brother who also had a variant in SCN1B (c.632G>A) and KCNQ2 (c.1870G>A) genes.
CONCLUSIONS Developmental delay, epileptic seizures and motor dysfunction are features frequently associated to paroxysmal hemiplegic attacks. Hemiplegic episode is only a sign even if the most remarkable of several neurological comorbidities in AHC carriers. Therefore, we suggest that the view of the disorder should be greatly changed to the term “AHC spectrum disorder". The comparison of molecular analysis among the four probands brings out how the genetic framework is not recurrent, but may result from an unexpected greater genetic heterogeneity, such as seen in siblings carrying a new set of gene variants implicated in channelopathies likely to be eligible as further risk factors for AHC.
Keywords
Alternating Hemiplegia of Childhood (AHC), Epilepsy, Developmental Delay, Flunarizine, ATP1A3, GRIN2A, SCN1B, KCNQ2
Figure 1
Figure 2
Figure 3
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Peer Review Timeline
CURRENT STATUS: Under Review
Editorial decision: Major revision
On 07 Dec, 2020
Reviewer #2 agreed
On 06 Dec, 2020
Review #2 received
Received 06 Dec, 2020
Review #1 received
Received 27 Nov, 2020
Reviewer #1 agreed
On 23 Nov, 2020
Reviewers invited
Invitations sent on 16 Nov, 2020
Editor assigned
On 10 Nov, 2020
Submission checks complete
On 10 Nov, 2020
Editor invited
On 10 Nov, 2020
Version 1
Posted 21 Sep, 2020
No community comments so far
Review #2 received
Received 18 Oct, 2020
Editorial decision: Major revision
On 18 Oct, 2020
Review #1 received
Received 08 Oct, 2020
Reviewer #2 agreed
On 06 Oct, 2020
Reviewers invited
Invitations sent on 23 Sep, 2020
Reviewer #1 agreed
On 23 Sep, 2020
Editor assigned
On 18 Sep, 2020
Editor invited
On 17 Sep, 2020
Submission checks complete
On 17 Sep, 2020
First submitted
On 16 Sep, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Pediatrics
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This preprint is under consideration at Italian Journal of Pediatrics. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Case report
Alternating Hemiplegia of Childhood and Neurological Comorbidities. Variable Intrafamilial Clinical Features.
Piero Pavone
University of Catania
Corresponding Author
ORCiD: https://orcid.org/0000-0002-5600-9560
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Editorial decision: Major revision
On 07 Dec, 2020
Reviewer #2 agreed
On 06 Dec, 2020
Review #2 received
Received 06 Dec, 2020
Review #1 received
Received 27 Nov, 2020
Reviewer #1 agreed
On 23 Nov, 2020
Reviewers invited
Invitations sent on 16 Nov, 2020
Editor assigned
On 10 Nov, 2020
Submission checks complete
On 10 Nov, 2020
Editor invited
On 10 Nov, 2020
Version 1
Posted 21 Sep, 2020
No community comments so far
Review #2 received
Received 18 Oct, 2020
Editorial decision: Major revision
On 18 Oct, 2020
Review #1 received
Received 08 Oct, 2020
Reviewer #2 agreed
On 06 Oct, 2020
Reviewers invited
Invitations sent on 23 Sep, 2020
Reviewer #1 agreed
On 23 Sep, 2020
Editor assigned
On 18 Sep, 2020
Editor invited
On 17 Sep, 2020
Submission checks complete
On 17 Sep, 2020
First submitted
On 16 Sep, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Pediatrics
License:
This work is licensed under a CC BY 4.0 License. Read Full License
BACKGROUND Alternating Hemiplegia of Childhood (AHC) is an uncommon and complex disorder characterized by age of onset before 18 months, recurrent hemiplegia of one or either sides of the body or quadriplegia. Developmental delay, epilepsy, tonic or dystonic spells, nystagmus and autonomic manifestations are frequently reported manifestations. AHC is mainly caused by mutations in ATP1A3 gene, and to a lesser extent in ATP1A2 gene.
CASE PRESENTATION Clinical and genetic findings of a couple of twins and a couple of siblings affected by AHC from two different Italian families were deeply examined. Intrafamilial clinical variability was shown in the present cases. A pathogenic variant rs606231437 in ATP1A3 gene was detected in twins, while in one of the siblings was found a novel variant of GRIN2A (c.3175T>A) gene, shared by the other brother who also had a variant in SCN1B (c.632G>A) and KCNQ2 (c.1870G>A) genes.
CONCLUSIONS Developmental delay, epileptic seizures and motor dysfunction are features frequently associated to paroxysmal hemiplegic attacks. Hemiplegic episode is only a sign even if the most remarkable of several neurological comorbidities in AHC carriers. Therefore, we suggest that the view of the disorder should be greatly changed to the term “AHC spectrum disorder". The comparison of molecular analysis among the four probands brings out how the genetic framework is not recurrent, but may result from an unexpected greater genetic heterogeneity, such as seen in siblings carrying a new set of gene variants implicated in channelopathies likely to be eligible as further risk factors for AHC.
Figure 1
Figure 2
Figure 3
Due to technical limitations, tables 1-3 are only available as a download in the Supplemental Files section.