Peripheral muscle weakness in RASopathies.
BACKGROUND
RASopathies are a group of genetic conditions due to alterations of the Ras/MAPK pathway. Neurocutaneous findings are hallmark features of the RASopathies, but musculoskeletal abnormalities are also frequent. The objective was to evaluate handgrip strength in the RASopathies.


METHODS
Individuals with RASopathies (e.g., Noonan syndrome, Costello syndrome, cardio-facio-cutaneous [CFC] syndrome, and neurofibromatosis type 1 [NF1]) and healthy controls were evaluated. Two methods of handgrip strength were tested: GRIP-D Takei Hand Grip Dynamometer and the Martin vigorimeter. A general linear model was fitted to compare average strength among the groups, controlling for confounders such as age, gender, height, and weight.


RESULTS
Takei dynamometer: handgrip strength was decreased in each of the syndromes compared with controls. Decreased handgrip strength compared with sibling controls was also seen with the Martin vigorimeter (P < 0.0001).


CONCLUSIONS
Handgrip strength is decreased in the RASopathies. The etiology of the reduced muscle force is unknown, but likely multifactorial.
University of Utah, Division of Medical Genetics, 2C412 SOM, Salt Lake City, Utah 84132, USA. david.stevenson@hsc.utah.edu
David A
DA
Stevenson
Shawn
S
Allen
William E
WE
Tidyman
John C
JC
Carey
David H
DH
Viskochil
Austin
A
Stevens
Heather
H
Hanson
Xiaoming
X
Sheng
Brandi A
BA
Thompson
Megumi J
MJ
Okumura
Kent
K
Reinker
Barbara
B
Johnson
Katherine A
KA
Rauen
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D056685:Costello Syndrome / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D004476:Ectodermal Dysplasia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D019066:Facies; D005183:Failure to Thrive / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D018737:Hand Strength / Q000502:physiology*; D006330:Heart Defects, Congenital / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D008875:Middle Aged; D018908:Muscle Weakness / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology; D009456:Neurofibromatosis 1 / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D009634:Noonan Syndrome / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
D018631:ras Proteins