This subject has come up from time to time in this group... and I thought this
abstract was interesting.. suggesting that there is some proof to back up the
thoughts of increased severity...

NOTE: Just because this study was done on 1A, it doesn't mean that it is limited
to only 1A... just that 1A was the sub-type that was subject of this study..

Anyone here find that later generations are affected more severely?



http://www.ncbi.nlm.nih.gov/pubmed/18438698?ordinalpos=1&itool=EntrezSystem2.PEn\
trez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpo\
s=3&log$=relatedarticles&logdbfrom=pubmed


: J Neurol. 2008 Jun;255(6):813-9. Epub 2008 Apr 30

Increased severity over generations of Charcot-Marie-Tooth disease type 1A.
Steiner I, Gotkine M, Steiner-Birmanns B, Biran I, Silverstein S, Abeliovich D,
Argov Z, Wirguin I.
Neurological Sciences Unit, Hadassah University Hospital, Mount Scopus, 24035,
Jerusalem 91240, Israel. isteiner@...

BACKGROUND: Charcot-Marie-Tooth type 1A (CMT1A) is an autosomal dominant
polyneuropathy due to a 1.5 Mb tandem duplication in chromosome 17p11.2,
containing the PMP22 gene. This mutation is not modified during inheritance.

OBJECTIVES: We set forth to test the hypothesis that in a subgroup of CMT1A
patients there is clinical anticipation, namely an increase in disease severity
over generations.

METHODS: Thirty-nine CMT1A mutation-positive patients in 16 families and 23
parent-offspring pairs were evaluated. This included 14 families with 2
generations and 2 families with 3 generations. Age of presentation was assessed
by interviewing the patients and clinical severity was measured using the CMT
neuropathy score (CMTNS).

RESULTS: In 21/23 parent-child pairs and 14/16 families, there was an earlier
age of presentation in children of genetically affected parents. The mean age of
onset in the progeny was 12.61 years compared to 41.22 years in the parent
generation, (p < 0.001).Mean severity in the younger generation was slightly
higher than that of the parent generation. When corrected for the age
difference, the trend for a worse phenotype in the younger generation became
statistically significant (p < 0.02,Wilcoxon signed rank test).

CONCLUSIONS: Our findings suggest that in a subgroup of CMT1A patients there is
an increase in clinical severity over generations. The mechanism responsible for
this observation remains unknown. Our findings should be validated on a larger
cohort of CMT1A families.

PMID: 18438698 [PubMed - indexed for MEDLINE


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