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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.

IntroductionSchaaf-Yang syndrome (SYS) is caused by truncating point mutations of the paternal allele of MAGEL2, an imprinted gene located in the critical region of Prader-Willi syndrome (PWS). These patients present a phenotype with neurodevelopmental delay, hypotonia, joint contractures, and a particularly high prevalence of autism (up to 75% in affected individuals). The loss of function of MAGEL2 is suggested to contribute to endocrine hypothalamic dysfunction in individuals with PWS.Case PresentationThe current study presented the case of a patient with SYS and a novel de novo truncating mutation of MAGEL2 and phenotypic characteristics typical of this Prader-Willi-like syndrome and also including partial hypopituitarism, hypothyroidism, growth hormone deficiency, and hyperprolactinemia.ConclusionsThe clinical and molecular similarities between SYS and PWS suggested the need for a thorough endocrinological follow-up to improve the prognosis and long-term quality of life for patients with SYS.