暂无摘要。

Charcot-Marie-Tooth Disease type 1A (CMT1A), the most common inherited peripheral neuropathy, is characterized by progressive sensory loss and weakness, which results in impaired mobility. Increased understanding of the genetics and pathophysiology of CMT1A has led to development of potential therapeutic agents, necessitating clinical trial readiness. Wearable sensors may provide useful outcome measures for future trials.
Individuals with CMT1A and unaffected controls were recruited for this 12-month study. Participants wore sensors for in-clinic assessments and at-home, from which activity, gait, and balance metrics were derived. Mann-Whitney U tests were used to analyze group differences for activity, gait, and balance parameters. Test-retest reliability of gait and balance parameters and correlations of these parameters with clinical outcome assessments (COAs) were examined.
Thirty individuals, 15 CMT1A, and 15 controls, participated. Gait and balance metrics demonstrated moderate to excellent reliability. CMT1A participants had longer step durations (p < .001), shorter step lengths (p = .03), slower gait speeds (p < .001), and greater postural sway (p < .001) than healthy controls. Moderate correlations were found between CMT-Functional Outcome Measure and step length (r = -0.59; p = .02), and gait speed (r = 0.64; p = .01); 11 out of 15 CMT1A participants demonstrated significant increases in stride duration between the first and last quarter of the 6-min walk test, suggesting fatigue.
In this initial study, gait and balance metrics derived from wearable sensors were reliable and associated with COAs in individuals with CMT1A. Larger longitudinal studies are needed to confirm our findings and evaluate sensitivity and utility of these disease-specific algorithms for clinical trial use.

UNASSIGNED: Recessive mutations in the gene encoding the histidine triad nucleotide-binding protein 1 (HINT1) are associated with axonal motor-predominant Charcot-Marie-Tooth (CMT) disease with neuromyotonia. A total of 24 HINT1 gene mutations have been reported so far. Some of these cases had mild to moderate elevations of creatinine kinase with no earlier reports of muscle biopsy findings in these cases. In this study, we describe a patient with axonal motor-predominant neuropathy and myopathy with rimmed vacuoles, likely due to a novel HINT1 gene mutation.
UNASSIGNED: A 35-year-old African American man presented with insidious onset and progressive symmetric distal leg weakness followed by hand muscle atrophy and weakness since the age of 25. He had no muscle cramps or sensory complaints. His 38-year-old brother developed similar symptoms beginning in his early 30 s. On neurologic examination, the patient had distal weakness and atrophy in all limbs, claw hands, pes cavus, absent Achilles reflexes, and normal sensory examination. Electrodiagnostic studies revealed absent/reduced compound motor action potential amplitudes distally with normal sensory responses with no neuromyotonia. His sural nerve biopsy showed a chronic non-specific axonal neuropathy, and a biopsy of the tibialis anterior muscle demonstrated myopathic features and several muscle fibers harboring rimmed vacuoles without inflammation in addition to chronic denervation changes. A homozygous variant, p.I63N (c.188T > A), in the HINT1 gene was found in both brothers.
UNASSIGNED: We describe a novel, likely pathogenic, HINT1 pI63N (c.188T > A) homozygous variant associated with hereditary axonal motor-predominant neuropathy without neuromyotonia in two African American brothers. The presence of rimmed vacuoles on muscle biopsy raises the possibility that mutations in the HINT1 gene may also cause myopathy.

OBJECTIVE: CMT is a group of heterogeneous motor and sensory neuropathies divided into demyelinating (CMT1) and axonal forms (CMT2). Distal Hereditary Motor Neuropathy (dHMN) is a motor neuropathy/neuronopathy which resembles CMT. Final genetic diagnosis is poor in CMT2 and in dHMN when compared with CMT1. Our aim is to report clinical, neurophysiological and genetic findings in a cohort of patients with axonal inherited neuropathies.
METHODS: We report clinical, neurophysiological and genetic findings from 45 patients with CMT2 or dHMN, coming from 39 unrelated families, observed in our Institute of Neurology over a 20-year period.
RESULTS: Clinical and electrophysiological examinations showed that 38 patients had CMT2 and 7 patients presented dHMN. Extensive genetic evaluation showed 6 mutations in MFN2, 4 mutations in HSPB1, 2 mutations in BSCL2, 3 mutations in GJB1, 1 mutation in MPZ.
CONCLUSIONS: Since next-generation sequencing will not be easily accessible, epidemiological data and clinical \"phenotyping\" remain the best strategy for clinicians to reach a correct genetic diagnosis in CMT2 and dHMN patients.