Pseudoxanthoma elasticum-like phenotype with cutis laxa and multiple coagulation factor deficiency represents a separate genetic entity.
Data on six patients with a Pseudoxanthoma Elasticum (PXE)-like phenotype, characterized by excessive skin folding (resembling cutis laxa) and a deficiency of the vitamin K-dependent clotting factors (II, VII, IX, and X) are presented. A comparison is made between the clinical, ultrastructural, and molecular findings in these patients and those seen in classic PXE and cutis laxa, respectively. Clinical overlap with PXE is obvious from the skin manifestations of yellowish papules or leathery plaques with dot-like depressions at presentation, angioid streaks and/or ocular peau d'orange, and fragmentation and calcification of elastic fibers in the dermis. Important phenotypic differences with PXE include much more severe skin laxity with spreading toward the trunk and limbs with thick, leathery skin folds rather than confinement to flexural areas, and no decrease in visual acuity. Moreover, detailed electron microscopic analyses revealed that alterations of elastic fibers as well as their mineralization were slightly different from those in classic PXE. Molecular analysis revealed neither causal mutations in the ABCC6 gene (ATP-binding cassette subfamily C member 6), which is responsible for PXE, nor in VKORC1 (vitamin K 2,3 epoxide reductase), known to be involved in vitamin K-dependent factor deficiency. However, the GGCX gene (gamma-glutamyl carboxylase), encoding an enzyme important for gamma-carboxylation of gla-proteins, harbored mutations in six out of seven patients analyzed. These findings all support the hypothesis that the disorder indeed represents a separate clinical and genetic entity, the molecular background of which remains to be unraveled.
Vanakker
Olivier M
OM
Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
Martin
Ludovic
L
Gheduzzi
Dealba
D
Leroy
Bart P
BP
Loeys
Bart L
BL
Guerci
Veronica I
VI
Matthys
Dirk
D
Terry
Sharon F
SF
Coucke
Paul J
PJ
Pasquali-Ronchetti
Ivonne
I
De Paepe
Anne
A
D000328:Adult; D001778:Blood Coagulation Disorders / Q000150:complications* / Q000175:diagnosis*; D001779:Blood Coagulation Factors / Q000378:metabolism*; D003483:Cutis Laxa / Q000175:diagnosis* / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods*; D020405:Dermis / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D010641:Phenotype; D011561:Pseudoxanthoma Elasticum / Q000175:diagnosis* / Q000235:genetics*; D012867:Skin / Q000473:pathology / Q000648:ultrastructure*; D012871:Skin Diseases / Q000145:classification* / Q000175:diagnosis* / Q000235:genetics; D014812:Vitamin K / Q000378:metabolism
D001779:Blood Coagulation Factors; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D014812:Vitamin K; C102029:ABCC6 protein, human