title: Asymptomatic homozygous protein C deficiency.
abstract: We report a family in which 2 homozygotes with similarly very low protein C levels have different clinical symptoms. One had recurrent venous thrombosis starting at the age of 28 years, the other is still asymptomatic at 38 years despite exposure to thrombotic risk factors. Our review of 13 additional cases reveals a highly variable phenotypic expression of homozygous protein C deficiency, which can be subdivided into two groups. In the first group are 8 kindreds in which homozygotes presented at birth with unmeasurable protein C levels and life-threatening thrombosis and 1 kindred in which homozygotes are characterized by very low levels of protein C but delayed onset (10 months of age) of thrombosis. In the second group are 4 kindreds characterized by very low, but measurable, protein C levels in homozygotes who survived beyond the neonatal period into adulthood with histories of moderately severe thrombosis. The present case demonstrates that protein C levels lower than 10% are compatible with a negative history for thrombosis, not only in the neonatal period but also during adulthood, and suggests that in some homozygotes other factors need to interact for full clinical penetrance of the defect.
authors.affiliation: A. Bianchi Bonomi Hemophilia and Thrombosis Center, University of Milan, Maggiore Hospital, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Tripodi
authors.forename: F
authors.initials: F
authors.lastname: Franchi
authors.forename: A
authors.initials: A
authors.lastname: Krachmalnicoff
authors.forename: P M
authors.initials: PM
authors.lastname: Mannucci
mesh_terms: D000328:Adult; D000368:Aged; D002648:Child; D005260:Female; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D010375:Pedigree; D020151:Protein C Deficiency; D012008:Recurrence; D013927:Thrombosis / Q000235:genetics*