Coagulation-factor deficiencies and abnormal bleeding in Noonan's syndrome.
Noonan's syndrome is characterised by a dysmorphic facies, congenital heart disease, and short stature, and is inherited as an autosomal dominant trait. Because abnormal bleeding has also been reported, we investigated a group of patients for coagulation-factor deficits. Of the 72 individuals studied (37 male, 35 female, mean age 11.4 years), 47 (65%) had a history of abnormal bruising or bleeding. 29 patients (40%) had a prolonged activated partial thromboplastin time. Specific abnormalities in the intrinsic pathway of coagulation (partial factor XI:C, XII:C, and VIII:C deficiencies) were found in 36 patients (50%). Multiple abnormalities among these 36 patients included combined factor XI:C and XII:C deficiencies (4 patients) and factor XI:C and VIII:C deficiencies (4), and 1 patient had combined factor VIII:C, XI:C, and XII:C deficiency. There was poor correlation between a history of abnormal bleeding and coagulation-factor deficit. In five families, similar coagulation-factor deficiencies were present in first-degree relatives with the syndrome. The pattern of inherited bleeding abnormalities seen in Noonan's syndrome suggests autosomal regulation of the intrinsic coagulation pathway.
South West Thames Regional Genetics Service, St George's Hospital Medical School, London, UK.
M
M
Sharland
M A
MA
Patton
S
S
Talbot
A
A
Chitolie
D H
DH
Bevan
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005173:Factor XI Deficiency / Q000097:blood*; D005175:Factor XII Deficiency / Q000097:blood*; D005190:Family; D005260:Female; D006467:Hemophilia A / Q000097:blood*; D006470:Hemorrhage / Q000097:blood*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009634:Noonan Syndrome / Q000097:blood* / Q000150:complications; D010314:Partial Thromboplastin Time; D011446:Prospective Studies