Pediatric inherited peripheral neuropathy: a prospective study at a Spanish referral center

Abstract Background Single‐center clinical series provide important information on genetic distribution that can guide genetic testing. However, there are few such studies on pediatric populations with inherited peripheral neuropathies (IPNs). Methods Thorough genetic testing was performed on IPN pa...

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Autores principales:	Herminia Argente‐Escrig, Marina Frasquet, Juan Francisco Vázquez‐Costa, Elvira Millet‐Sancho, Inmaculada Pitarch, Miguel Tomás‐Vila, Carmen Espinós, Vincenzo Lupo, Teresa Sevilla
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/e186954ae6ca469abefce9e51e1e24eb
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spelling	oai:doaj.org-article:e186954ae6ca469abefce9e51e1e24eb2021-11-19T13:55:31ZPediatric inherited peripheral neuropathy: a prospective study at a Spanish referral center2328-950310.1002/acn3.51432https://doaj.org/article/e186954ae6ca469abefce9e51e1e24eb2021-09-01T00:00:00Zhttps://doi.org/10.1002/acn3.51432https://doaj.org/toc/2328-9503Abstract Background Single‐center clinical series provide important information on genetic distribution that can guide genetic testing. However, there are few such studies on pediatric populations with inherited peripheral neuropathies (IPNs). Methods Thorough genetic testing was performed on IPN patients under 20 years of age from a geographically well‐defined Mediterranean area (Valencian Community, Spain), annually assessed with the Charcot–Marie–Tooth disease Pediatric Scale (CMTPedS). Results From 86 families with IPNs, 99 patients (59 males) were identified, 85 with sensorimotor neuropathy or CMT (2/3 demyelinating form) and 14 with distal hereditary motor neuropathy (dHMN). Genetic diagnosis was achieved in 79.5% families, with a similar mutation detection rate in the demyelinating (88.7%) and axonal (89.5%) forms, significantly higher than in the dHMN families (27.3%). CMT1A was the most common subtype, followed by those carrying heterozygous mutations in either the GDAP1 or GJB1 genes. Mutations in 15 other genes were identified, including a new pathogenic variant in the ATP1A gene. The CMTPedS detected significant disease progression in all genetic subtypes of CMT, at a rate of 1.84 (±3.7) over 1 year (p < 0.0005, n = 62) and a 2‐year rate of 3.6 (±4.4: p < 0.0005, n = 45). Significant disease worsening was also detected for CMT1A over 1 (1.7 ± 3.6, p < 0.05) and 2 years (4.2 ± 4.3, p < 0.0005). Conclusions This study highlights the unique spectrum of IPN gene frequencies among pediatric patients in this specific geographic region, identifying the CMTPedS as a sensitive tool to detect significant disease worsening over 1 year that could help optimize the design of clinical trials.Herminia Argente‐EscrigMarina FrasquetJuan Francisco Vázquez‐CostaElvira Millet‐SanchoInmaculada PitarchMiguel Tomás‐VilaCarmen EspinósVincenzo LupoTeresa SevillaWileyarticleNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENAnnals of Clinical and Translational Neurology, Vol 8, Iss 9, Pp 1809-1816 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Herminia Argente‐Escrig Marina Frasquet Juan Francisco Vázquez‐Costa Elvira Millet‐Sancho Inmaculada Pitarch Miguel Tomás‐Vila Carmen Espinós Vincenzo Lupo Teresa Sevilla Pediatric inherited peripheral neuropathy: a prospective study at a Spanish referral center
description	Abstract Background Single‐center clinical series provide important information on genetic distribution that can guide genetic testing. However, there are few such studies on pediatric populations with inherited peripheral neuropathies (IPNs). Methods Thorough genetic testing was performed on IPN patients under 20 years of age from a geographically well‐defined Mediterranean area (Valencian Community, Spain), annually assessed with the Charcot–Marie–Tooth disease Pediatric Scale (CMTPedS). Results From 86 families with IPNs, 99 patients (59 males) were identified, 85 with sensorimotor neuropathy or CMT (2/3 demyelinating form) and 14 with distal hereditary motor neuropathy (dHMN). Genetic diagnosis was achieved in 79.5% families, with a similar mutation detection rate in the demyelinating (88.7%) and axonal (89.5%) forms, significantly higher than in the dHMN families (27.3%). CMT1A was the most common subtype, followed by those carrying heterozygous mutations in either the GDAP1 or GJB1 genes. Mutations in 15 other genes were identified, including a new pathogenic variant in the ATP1A gene. The CMTPedS detected significant disease progression in all genetic subtypes of CMT, at a rate of 1.84 (±3.7) over 1 year (p < 0.0005, n = 62) and a 2‐year rate of 3.6 (±4.4: p < 0.0005, n = 45). Significant disease worsening was also detected for CMT1A over 1 (1.7 ± 3.6, p < 0.05) and 2 years (4.2 ± 4.3, p < 0.0005). Conclusions This study highlights the unique spectrum of IPN gene frequencies among pediatric patients in this specific geographic region, identifying the CMTPedS as a sensitive tool to detect significant disease worsening over 1 year that could help optimize the design of clinical trials.
format	article
author	Herminia Argente‐Escrig Marina Frasquet Juan Francisco Vázquez‐Costa Elvira Millet‐Sancho Inmaculada Pitarch Miguel Tomás‐Vila Carmen Espinós Vincenzo Lupo Teresa Sevilla
author_facet	Herminia Argente‐Escrig Marina Frasquet Juan Francisco Vázquez‐Costa Elvira Millet‐Sancho Inmaculada Pitarch Miguel Tomás‐Vila Carmen Espinós Vincenzo Lupo Teresa Sevilla
author_sort	Herminia Argente‐Escrig
title	Pediatric inherited peripheral neuropathy: a prospective study at a Spanish referral center
title_short	Pediatric inherited peripheral neuropathy: a prospective study at a Spanish referral center
title_full	Pediatric inherited peripheral neuropathy: a prospective study at a Spanish referral center
title_fullStr	Pediatric inherited peripheral neuropathy: a prospective study at a Spanish referral center
title_full_unstemmed	Pediatric inherited peripheral neuropathy: a prospective study at a Spanish referral center
title_sort	pediatric inherited peripheral neuropathy: a prospective study at a spanish referral center
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/e186954ae6ca469abefce9e51e1e24eb
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Pediatric inherited peripheral neuropathy: a prospective study at a Spanish referral center

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