Overlap Phenotype between CMT1A and Hereditary Neuropathy with Liability to Pressure Palsies Caused by the Novel Small In-frame Deletion c.407_418del12 in PMP22 Gene

Abstract

We report monozygotic twins, who presented with a clinical picture of Charcot-Marie-Tooth disease type 1 (CMT1) with bilateral foot drop, pes cavus, thoracic kyphosis, and scoliosis. Hereditary neuropathy with liability to pressure palsies (HNPP) showed up in one of them. Neurography showed demyelinating neuropathy, typical for CMT1, and transient conduction block in the ulnar nerve correlating with clinical ulnar palsy due to minor mechanical stress in only one of them. Genetic analysis revealed novel small de novo deletion c.407_418del12 in the PMP22 gene. Our patient shows the rarely reported combination of CMT1A and HNPP, caused by an in-frame deletion in the PMP22 gene. HNPP is in the majority of cases correlated with heterozygous deletion of the whole PMP22 gene or other mutations leading to functional haploinsufficiency. The cases give further evidence that pathogenesis of HNPP is not completely understood and can obviously result from existence of a defective protein, too. The intrafamiliar phenotypic variability, even in monozygotic twins, confirms the well-known fact that factors apart from genetics contribute to the clinical course.

Anesthetic Considerations for Patients with Hereditary Neuropathy with Liability to Pressure Palsies: A Narrative Review

“…HNPP can be further organized into three distinct groups. The fir form results from a duplication of the PMP22 gene giving rise to Charcot-Marie-Toot disease type 1A (CMT1A) [6,14]. A subset of said CMT1A patients exhibit a mutation:…”

“…The condition also demonstrates significant variability in its observable characteristics, which makes it challenging to precisely estimate the incidence of the illness. Notably, even among monozygotic twins, variations in both observable traits and electrodiagnostic features have been observed [6]. Mechanisms underlying the emergence of HNPP secondary to mutations in PMP22 are complex and may be unique to each specific human genome [7,8].…”

“…HNPP can be further organized into three distinct groups. The first form results from a duplication of the PMP22 gene giving rise to Charcot-Marie-Tooth disease type 1A (CMT1A) [6,14]. A subset of said CMT1A patients exhibit a mutation: a LITAF I92V sequence that leads to accumulation of PMP22 in mitochondria, leading to cellular accumulation rather than directing it to lysosomes for proper processing [16].…”

Conduction block as an electrophysiological phenomenon: a review of the literature

“…БП при НМСН 1А выявляются редко, в литературе описано несколько случаев, «атипичных» по обнаруженным ЭМГ-изменениям и характеру течения болезни [59,60]. Представлены наблюдения пациентов с одновременным развитием НМСН 1А и ННПС с БП [61]. Описаны единичные случаи выявления БП при НМСН, обусловленных мутациями в генах MPZ, LITAF и GJ1B [59].…”