Early Onset Inherited Peripheral Neuropathies: The Experience of a Specialized Referral Center for Genetic Diagnosis Achievement.

Autor:	Geroldi A; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences, University of Genoa, Genoa, Italy. Electronic address: alessandro.geroldi@unige.it., Ponti C; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, UOC Genetica Medica, Genoa, Italy., Mammi A; IRCCS Ospedale Policlinico San Martino, UOC Genetica Medica, Genoa, Italy., Patrone S; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences, University of Genoa, Genoa, Italy., Gotta F; IRCCS Ospedale Policlinico San Martino, UOC Genetica Medica, Genoa, Italy., Trevisan L; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, UOC Genetica Medica, Genoa, Italy., Sanguineri F; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, UOC Genetica Medica, Genoa, Italy., Origone P; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, UOC Genetica Medica, Genoa, Italy., Gaudio A; IRCCS Ospedale Policlinico San Martino, UOC Genetica Medica, Genoa, Italy., La Barbera A; IRCCS Ospedale Policlinico San Martino, UOC Genetica Medica, Genoa, Italy., Cataldi M; Pediatric Neuropsychiatric Unit, IRCCS Institute 'G. Gaslini', Genoa, Italy., Gemelli C; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, UOC Clinica Neurologica, Genoa, Italy., Massucco S; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, UOC Clinica Neurologica, Genoa, Italy., Schenone A; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, UOC Clinica Neurologica, Genoa, Italy., Lanteri P; Pediatric Neuropsychiatric Unit, IRCCS Institute 'G. Gaslini', Genoa, Italy., Fiorillo C; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences, University of Genoa, Genoa, Italy; Unit of Paediatric Neurology and Neuromuscular Disorders, IRCCS Institute 'G. Gaslini', Genoa, Italy., Grandis M; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, UOC Clinica Neurologica, Genoa, Italy., Mandich P; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, UOC Genetica Medica, Genoa, Italy., Bellone E; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, UOC Genetica Medica, Genoa, Italy.
Jazyk:	angličtina
Zdroj:	Pediatric neurology [Pediatr Neurol] 2024 May; Vol. 154, pp. 4-8. Date of Electronic Publication: 2024 Feb 10.
DOI:	10.1016/j.pediatrneurol.2024.02.002
Abstrakt:	Background: Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of inherited peripheral neuropathies. Although the typical disease onset is reported in the second decade, earlier onsets are not uncommon. To date, few studies on pediatric populations have been conducted and the achievement of molecular diagnosis remains challenging. Methods: During the last 24 years we recruited 223 patients with early-onset hereditary peripheral neuropathies (EOHPN), negative for PMP22 duplication, 72 of them referred by a specialized pediatric hospital. Genetic testing for CMT-associated genes has been carried out with a range of different techniques. Results: Of the 223 EOHPN cases, 43% were classified as CMT1 (demyelinating), 49% as CMT2 (axonal), and 8% as CMTi (intermediate). Genetic diagnosis was reached in 51% of patients, but the diagnostic yield increased to 67% when focusing only on cases from the specialized pediatric neuromuscular centers. Excluding PMP22 rearrangements, no significant difference in diagnostic rate between demyelinating and axonal forms was identified. De novo mutations account for 38% of cases. Conclusions: This study describes an exhaustive picture of EOHPN in an Italian referral genetic center and analyzes the molecular diagnostic rate of a heterogeneous cohort compared with one referred by a specialized pediatric center. Our data identify MPZ, MFN2, GDAP1, and SH3TC2 genes as the most frequent players in EOHPN. Our study underlines the relevance of a specific neurological pediatric expertise to address the genetic testing and highlights its importance to clarify possible unexpected results when neuropathy is only a secondary clinical sign of a more complex phenotype. Competing Interests: Declaration of competing interest None. (Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu Full Text from ScienceDirect