Late-onset hereditary axonal neuropathies.

Area of Science:

• Neurology
• Genetics
• Peripheral Nervous System Disorders

Background:

• Hereditary motor-sensory neuropathy, or Charcot-Marie-Tooth (CMT) syndrome, exhibits significant genetic heterogeneity.
• Typical onset occurs in childhood, adolescence, or young adulthood.

Purpose of the Study:

• To define and characterize late-onset forms of hereditary motor-sensory neuropathy.
• Investigate the clinical and genetic features of peripheral neuropathies with late onset.

Main Methods:

• Conducted a clinical and genetic study of families with uniformly late-onset peripheral neuropathy.
• Performed extensive mutation screening of nine known Charcot-Marie-Tooth genes.

Main Results:

• Identified six families with late-onset, primarily axonal peripheral neuropathy (median onset age 57 years).
• Observed mixed motor and sensory neuropathy with axonal, not demyelinating, electrophysiologic characteristics.
• Noted a possible association with deafness; inheritance patterns included autosomal dominant and sporadic cases. Mutation screening was negative for known CMT genes.

Conclusions:

• Late-onset hereditary axonal neuropathies exist as a distinct clinical entity.
• The genetic underpinnings of these late-onset forms are currently unknown.
• Significant genetic heterogeneity is likely responsible for these late-onset conditions.