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Hereditary neuropathy with liability to pressure palsies (HNPP): Intrafamilial phenotypic variability and early childhood refusal to walk as the presenting symptom

BACKGROUND: Limping and/or refusal to walk is a common complaint in the setting of the pediatric department, with a widely diverse differential diagnosis. An unusual etiology, is that of a hereditary neuropathy. Hereditary neuropathy with liability to pressure palsies (HNPP) is a recurrent, episodic...

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Autores principales: Karklinsky, Shani, Kugler, Shir, Bar-Yosef, Omer, Nissenkorn, Andreea, Grossman-Jonish, Anat, Tirosh, Irit, Vivante, Asaf, Pode-Shakked, Ben
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9164845/
https://www.ncbi.nlm.nih.gov/pubmed/35658923
http://dx.doi.org/10.1186/s13052-022-01280-z
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author Karklinsky, Shani
Kugler, Shir
Bar-Yosef, Omer
Nissenkorn, Andreea
Grossman-Jonish, Anat
Tirosh, Irit
Vivante, Asaf
Pode-Shakked, Ben
author_facet Karklinsky, Shani
Kugler, Shir
Bar-Yosef, Omer
Nissenkorn, Andreea
Grossman-Jonish, Anat
Tirosh, Irit
Vivante, Asaf
Pode-Shakked, Ben
author_sort Karklinsky, Shani
collection PubMed
description BACKGROUND: Limping and/or refusal to walk is a common complaint in the setting of the pediatric department, with a widely diverse differential diagnosis. An unusual etiology, is that of a hereditary neuropathy. Hereditary neuropathy with liability to pressure palsies (HNPP) is a recurrent, episodic demyelinating neuropathy, most commonly caused by a 17p11.2 chromosomal deletion encompassing the PMP22 gene. METHODS: We pursued chromosomal microarray analysis (CMA) in multiple affected individuals of a single extended family, manifesting a range of phenotypic features consistent with HNPP. RESULTS: A 4.5 years-old boy presented for in-patient evaluation due to refusal to walk. Initial investigations including spine MRI and bone scan failed to yield a conclusive diagnosis. Following family history, which implied an autosomal dominant mode of inheritance, CMA was pursued and confirmed a 17p11.2 deletion in the proband consistent with HNPP. Importantly, following this diagnosis, four additional affected family members were demonstrated to harbor the deletion. Their variable phenotypic features, ranging from a prenatal diagnosis of a 6 months-old sibling, to recurrent paresthesias manifesting in the fourth decade of life, are discussed. CONCLUSIONS: Our experience with the family reported herein demonstrates how a thorough anamnesis can lead to a rare genetic etiology with a favorable prognosis and prevent unnecessary investigations, and underscores HNPP as an uncommon diagnostic possibility in the limping child.
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spelling pubmed-91648452022-06-05 Hereditary neuropathy with liability to pressure palsies (HNPP): Intrafamilial phenotypic variability and early childhood refusal to walk as the presenting symptom Karklinsky, Shani Kugler, Shir Bar-Yosef, Omer Nissenkorn, Andreea Grossman-Jonish, Anat Tirosh, Irit Vivante, Asaf Pode-Shakked, Ben Ital J Pediatr Research BACKGROUND: Limping and/or refusal to walk is a common complaint in the setting of the pediatric department, with a widely diverse differential diagnosis. An unusual etiology, is that of a hereditary neuropathy. Hereditary neuropathy with liability to pressure palsies (HNPP) is a recurrent, episodic demyelinating neuropathy, most commonly caused by a 17p11.2 chromosomal deletion encompassing the PMP22 gene. METHODS: We pursued chromosomal microarray analysis (CMA) in multiple affected individuals of a single extended family, manifesting a range of phenotypic features consistent with HNPP. RESULTS: A 4.5 years-old boy presented for in-patient evaluation due to refusal to walk. Initial investigations including spine MRI and bone scan failed to yield a conclusive diagnosis. Following family history, which implied an autosomal dominant mode of inheritance, CMA was pursued and confirmed a 17p11.2 deletion in the proband consistent with HNPP. Importantly, following this diagnosis, four additional affected family members were demonstrated to harbor the deletion. Their variable phenotypic features, ranging from a prenatal diagnosis of a 6 months-old sibling, to recurrent paresthesias manifesting in the fourth decade of life, are discussed. CONCLUSIONS: Our experience with the family reported herein demonstrates how a thorough anamnesis can lead to a rare genetic etiology with a favorable prognosis and prevent unnecessary investigations, and underscores HNPP as an uncommon diagnostic possibility in the limping child. BioMed Central 2022-06-03 /pmc/articles/PMC9164845/ /pubmed/35658923 http://dx.doi.org/10.1186/s13052-022-01280-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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
Karklinsky, Shani
Kugler, Shir
Bar-Yosef, Omer
Nissenkorn, Andreea
Grossman-Jonish, Anat
Tirosh, Irit
Vivante, Asaf
Pode-Shakked, Ben
Hereditary neuropathy with liability to pressure palsies (HNPP): Intrafamilial phenotypic variability and early childhood refusal to walk as the presenting symptom
title Hereditary neuropathy with liability to pressure palsies (HNPP): Intrafamilial phenotypic variability and early childhood refusal to walk as the presenting symptom
title_full Hereditary neuropathy with liability to pressure palsies (HNPP): Intrafamilial phenotypic variability and early childhood refusal to walk as the presenting symptom
title_fullStr Hereditary neuropathy with liability to pressure palsies (HNPP): Intrafamilial phenotypic variability and early childhood refusal to walk as the presenting symptom
title_full_unstemmed Hereditary neuropathy with liability to pressure palsies (HNPP): Intrafamilial phenotypic variability and early childhood refusal to walk as the presenting symptom
title_short Hereditary neuropathy with liability to pressure palsies (HNPP): Intrafamilial phenotypic variability and early childhood refusal to walk as the presenting symptom
title_sort hereditary neuropathy with liability to pressure palsies (hnpp): intrafamilial phenotypic variability and early childhood refusal to walk as the presenting symptom
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9164845/
https://www.ncbi.nlm.nih.gov/pubmed/35658923
http://dx.doi.org/10.1186/s13052-022-01280-z
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