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.
Sharland
M
M
South West Thames Regional Genetics Service, St George's Hospital Medical School, London, UK.
Patton
M A
MA
Talbot
S
S
Chitolie
A
A
Bevan
D H
DH
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