Charcot‐Marie‐Tooth 1A: A narrative review with clinical and anatomical perspectives

Abstract

Charcot-Marie-Tooth 1A (CMT1A) is regarded as the most common hereditary peripheral neurodegenerative disorder. This narrative review highlights perspectives around the historically well-established and characteristic anatomical manifestations of CMT1A seen in the feet, legs and hands, in addition to a clinical diagnosis that may be confirmed by electrophysiology, genetic or molecular markers together with the presence of a typical family history. A less well-known perspective is the potential for systemic manifestations and wider complication. The condition is characterised by a progressive clinical picture with unmistakable anatomical and neurological features that have been described since the late 19th century. There remains no cure although supportive, rehabilitative, and surgical regimes may provide helpful management or amelioration of symptoms. Most recently, the emergence of a pleotherapeutic approach suggests distinct promise. Future research focused on a detailed elucidation of the underlying molecular mechanisms underpinning myelin and axonal function may eventually hold the key to successful treatment of CMT1A. Genetic modification would potentially present a cure. Clin. Anat. 29:547-554, 2016. © 2015 Wiley Periodicals, Inc.

Nectin-like 4 Complexes with Choline Transporter-like Protein-1 and Regulates Schwann Cell Choline Homeostasis and Lipid Biogenesis in Vitro

“…In vitro studies have demonstrated that NECL4 is needed for myelination (8,10), and the delay in the onset of myelination observed in the in vivo NECL4 Ϫ/Ϫ mouse supports that finding (9). Most dramatic are the morphological abnormalities observed at 2 months of age, in particular focal hypermyelination with tomacula and myelin outfoldings that are characteristic of Charcot-Marie-Tooth neuropathies (9,50). In this study, we describe the complexing of NECL4 with CTL1 and the impact of NECL4 deficiency on choline-dependent metabolism in purified Schwann cells.…”

Clinical and Pathological Variation of Charcot-Marie-Tooth 1A in a Large Chinese Cohort

“…CMT1A is caused by duplication of the peripheral myelin protein 22 ( PMP22 ) gene accounting for more than half of all the CMT cases. The disease usually occurs in the second and third decades [ 2 ], with slowly progressive length-dependent neuropathy [ 3 , 4 ]. Dejerine-Sottas syndrome [ 5 , 6 ], or onset in the late adulthood, has been described occasionally.…”