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

Autor: Vincenzo Lupo, Juan F. Vázquez-Costa, Carmen Espinós, Miguel Tomás-Vila, Teresa Sevilla, Inmaculada Pitarch, Herminia Argente-Escrig, Elvira Millet-Sancho, Marina Frasquet
Rok vydání: 2021
Předmět:
Adult
Male
medicine.medical_specialty
ARYLSULFATASE
Adolescent
Neurosciences. Biological psychiatry. Neuropsychiatry
Disease
CHARCOT-MARIE-TOOTH
GUIDELINES
PHENOTYPE
VALIDATION
HEREDITARY NEUROPATHIES
Young Adult
Charcot-Marie-Tooth Disease
Internal medicine
medicine
Humans
Longitudinal Studies
Age of Onset
RC346-429
Child
Prospective cohort study
Referral and Consultation
Gene
Research Articles
Genetic testing
DISEASE FREQUENCY
medicine.diagnostic_test
MUTATIONS
Mediterranean Region
business.industry
General Neuroscience
Disease progression
Peripheral Nervous System Diseases
Inherited Peripheral Neuropathy
NATURAL-HISTORY
Clinical trial
Spain
Child
Preschool
Referral center
Female
Neurology. Diseases of the nervous system
Neurology (clinical)
Hereditary Sensory and Motor Neuropathy
business
RC321-571
GENETIC SUBTYPES
Research Article
Zdroj: Annals of Clinical and Translational Neurology
r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe
instname
r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)
Universitat Rovira i virgili (URV)
Annals of Clinical and Translational Neurology, Vol 8, Iss 9, Pp 1809-1816 (2021)
ISSN: 2328-9503
DOI: 10.1002/acn3.51432
Popis: 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.
Databáze: OpenAIRE
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