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Parental perspectives of episodic irritability in an ultra-rare genetic disorder associated with NACC1
BACKGROUND: A recurrent de novo variant (c.892C>T) in NACC1 causes a neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination (NECFM). An unusual and consistently reported feature is episodic extreme irritability and inconsolability. We now charact...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10476425/ https://www.ncbi.nlm.nih.gov/pubmed/37667351 http://dx.doi.org/10.1186/s13023-023-02891-3 |
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author | Schoch, Kelly McConkie-Rosell, Allyn Walley, Nicole Bhambhani, Vikas Feyma, Timothy Pizoli, Carolyn E. Smith, Edward C. Tan, Queenie K.-G. Shashi, Vandana |
author_facet | Schoch, Kelly McConkie-Rosell, Allyn Walley, Nicole Bhambhani, Vikas Feyma, Timothy Pizoli, Carolyn E. Smith, Edward C. Tan, Queenie K.-G. Shashi, Vandana |
author_sort | Schoch, Kelly |
collection | PubMed |
description | BACKGROUND: A recurrent de novo variant (c.892C>T) in NACC1 causes a neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination (NECFM). An unusual and consistently reported feature is episodic extreme irritability and inconsolability. We now characterize these episodes, their impact on the family, and ascertain treatments that may be effective. Parents of 14 affected individuals provided narratives describing the irritability episodes, including triggers, behavioral and physiological changes, and treatments. Simultaneously, parents of 15 children completed the Non-communicating Children’s Pain Checklist-Revised (NCCPC-R), a measure to assess pain in non-verbal children. RESULTS: The episodes of extreme irritability include a prodromal, peak, and resolving phase, with normal periods in between. The children were rated to have extreme pain-related behaviors on the NCCPC-R scale, although it is unknown whether the physiologic changes described by parents are caused by pain. Attempted treatments included various classes of medications, with psychotropic and sedative medications being most effective (7/15). Nearly all families (13/14) describe how the episodes have a profound impact on their lives. CONCLUSIONS: NECFM caused by the recurrent variant c.892C>T is associated with a universal feature of incapacitating episodic irritability of unclear etiology. Further understanding of the pathophysiology can lead to more effective therapeutic strategies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13023-023-02891-3. |
format | Online Article Text |
id | pubmed-10476425 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-104764252023-09-05 Parental perspectives of episodic irritability in an ultra-rare genetic disorder associated with NACC1 Schoch, Kelly McConkie-Rosell, Allyn Walley, Nicole Bhambhani, Vikas Feyma, Timothy Pizoli, Carolyn E. Smith, Edward C. Tan, Queenie K.-G. Shashi, Vandana Orphanet J Rare Dis Research BACKGROUND: A recurrent de novo variant (c.892C>T) in NACC1 causes a neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination (NECFM). An unusual and consistently reported feature is episodic extreme irritability and inconsolability. We now characterize these episodes, their impact on the family, and ascertain treatments that may be effective. Parents of 14 affected individuals provided narratives describing the irritability episodes, including triggers, behavioral and physiological changes, and treatments. Simultaneously, parents of 15 children completed the Non-communicating Children’s Pain Checklist-Revised (NCCPC-R), a measure to assess pain in non-verbal children. RESULTS: The episodes of extreme irritability include a prodromal, peak, and resolving phase, with normal periods in between. The children were rated to have extreme pain-related behaviors on the NCCPC-R scale, although it is unknown whether the physiologic changes described by parents are caused by pain. Attempted treatments included various classes of medications, with psychotropic and sedative medications being most effective (7/15). Nearly all families (13/14) describe how the episodes have a profound impact on their lives. CONCLUSIONS: NECFM caused by the recurrent variant c.892C>T is associated with a universal feature of incapacitating episodic irritability of unclear etiology. Further understanding of the pathophysiology can lead to more effective therapeutic strategies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13023-023-02891-3. BioMed Central 2023-09-04 /pmc/articles/PMC10476425/ /pubmed/37667351 http://dx.doi.org/10.1186/s13023-023-02891-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Schoch, Kelly McConkie-Rosell, Allyn Walley, Nicole Bhambhani, Vikas Feyma, Timothy Pizoli, Carolyn E. Smith, Edward C. Tan, Queenie K.-G. Shashi, Vandana Parental perspectives of episodic irritability in an ultra-rare genetic disorder associated with NACC1 |
title | Parental perspectives of episodic irritability in an ultra-rare genetic disorder associated with NACC1 |
title_full | Parental perspectives of episodic irritability in an ultra-rare genetic disorder associated with NACC1 |
title_fullStr | Parental perspectives of episodic irritability in an ultra-rare genetic disorder associated with NACC1 |
title_full_unstemmed | Parental perspectives of episodic irritability in an ultra-rare genetic disorder associated with NACC1 |
title_short | Parental perspectives of episodic irritability in an ultra-rare genetic disorder associated with NACC1 |
title_sort | parental perspectives of episodic irritability in an ultra-rare genetic disorder associated with nacc1 |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10476425/ https://www.ncbi.nlm.nih.gov/pubmed/37667351 http://dx.doi.org/10.1186/s13023-023-02891-3 |
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