Late-onset hereditary axonal neuropathies.
BACKGROUND
Hereditary motor-sensory neuropathy or the Charcot-Marie-Tooth syndrome is known to represent considerable genetic heterogeneity. Onset is usually in childhood, adolescence, or young adulthood. The objective of this study was to define late-onset forms of the disorder.


METHODS
A clinical and genetic study of families with uniformly late onset of peripheral neuropathy was performed in a university neurogenetics setting.


RESULTS
Six families were identified with consistently late onset of a primarily axonal neuropathy. Median age at symptom onset was 57 years (range 35-85 years) of a mixed motor and sensory neuropathy with electrophysiologic characteristics of an axonal rather than demyelinating condition. There was a possible association with deafness. Two families showed autosomal dominant inheritance whereas four families had only one affected generation with an excess of males. An extensive mutation screen of nine genes known to cause Charcot-Marie-Tooth was negative.


CONCLUSIONS
There are late-onset forms of hereditary axonal neuropathies. The genetic causes remain unknown and genetic heterogeneity within this entity is likely.
Bennett
C L
CL
Department of Pediatrics, University of Washington Medical School, Children's Hospital and Regional Medical Center, Seattle, WA, USA.
Lawson
V H
VH
Brickell
K L
KL
Isaacs
K
K
Seltzer
W
W
Lipe
H P
HP
Weiss
M D
MD
Carter
G T
GT
Flanigan
K M
KM
Chance
P F
PF
Bird
T D
TD
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D025063:Chromosome Disorders / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D004252:DNA Mutational Analysis; D004568:Electrodiagnosis / Q000592:standards; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D015417:Hereditary Sensory and Motor Neuropathy / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009431:Neural Conduction / Q000235:genetics; D010375:Pedigree; D010525:Peripheral Nerves / Q000473:pathology / Q000503:physiopathology*; D012737:Sex Factors