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Pediatric inherited peripheral neuropathy: a prospective study at a Spanish referral center
Herminia Argente-Escrig1,2,3,4, Marina Frasquet1,2,3,4, Juan Francisco Vázquez-Costa1,2,3,4
1Neuromuscular & Ataxias Research Group, Instituto de Investigación Sanitaria La Fe, Valencia, Spain.
Insights
This study reveals unique inherited peripheral neuropathy (IPN) gene frequencies in pediatric patients from Spain. The Charcot-Marie-Tooth disease Pediatric Scale (CMTPedS) effectively tracks disease progression in these children.
Area of Science:
- Genetics
- Neurology
- Pediatrics
Background:
- Limited studies exist on genetic distribution in pediatric inherited peripheral neuropathies (IPNs).
- Understanding genetic patterns is crucial for guiding genetic testing in children with IPNs.
Purpose of the Study:
- To investigate the genetic spectrum of IPNs in pediatric patients from a Mediterranean region.
- To evaluate the utility of the Charcot-Marie-Tooth disease Pediatric Scale (CMTPedS) in assessing disease progression.
Main Methods:
- Genetic testing was performed on pediatric IPN patients (<20 years) from the Valencian Community, Spain.
- Patients were annually assessed using the CMTPedS.
- Analysis included genetic diagnosis rates and disease progression over time.
Main Results:
- Genetic diagnosis was achieved in 79.5% of 86 families, with high detection rates for demyelinating and axonal forms.
- CMT1A was the most common subtype, followed by GDAP1 and GJB1 mutations.
- The CMTPedS showed significant disease worsening over 1 and 2 years across all CMT subtypes, including CMT1A.
Conclusions:
- The study identified a unique spectrum of IPN gene frequencies in pediatric patients in this region.
- The CMTPedS is a sensitive tool for detecting significant disease worsening in pediatric IPNs.
- Findings can inform genetic testing strategies and clinical trial design for pediatric IPNs.
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.
