title: Atypical presentation of pseudoxanthoma elasticum with abdominal cutis laxa: evidence for a spectrum of ectopic calcification disorders?
abstract: A patient is presented with severe cutis laxa of the abdomen. Molecular investigations, including sequencing of the fibulin-5 and elastin gene, failed to endorse the diagnosis of inherited cutis laxa. Ultrasonographical discovery of renal calcifications during his general work-up suggested a possible diagnosis of pseudo-xanthoma elasticum (PXE). A discrete yellowish reticular pattern in the anterior neck region was detected upon careful clinical examination. Clinically, the patient presented characteristics of both classic PXE (retinopathy, renal calcifications) and the PXE-like syndrome (cutis laxa beyond the flexural areas). Skin biopsy and ophthalmological examination confirmed the diagnosis of PXE. In addition, ultrastructural evaluation revealed calcium deposits in the periphery of elastic fibers, a typical observation in the PXE-like syndrome. Immunohistochemical experiments and ELISA tests for various inhibitors of calcification displayed results which were partly reminiscent of both PXE and the PXE-like syndrome. Molecular analysis revealed not only two ABCC6 mutations (related to PXE), but also a gain of function SNP in the GGCX gene, in which loss-of-function mutations cause the PXE-like syndrome. We conclude that the patients phenotype and--to a further extent--the PXE-like syndrome, are part of a spectrum of ectopic calcification disorders which are clinically and/or pathogenetically related to PXE. The molecular findings in this patient are however insufficient to explain the entire phenotype and suggest a role for multiple genetic factors in soft tissue mineralization.
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: Olivier M
authors.initials: OM
authors.lastname: Vanakker
authors.forename: Bart P
authors.initials: BP
authors.lastname: Leroy
authors.forename: Leon J
authors.initials: LJ
authors.lastname: Schurgers
authors.forename: Cees
authors.initials: C
authors.lastname: Vermeer
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Coucke
authors.forename: Anne
authors.initials: A
authors.lastname: De Paepe
mesh_terms: D000293:Adolescent; D002114:Calcinosis / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D025063:Chromosome Disorders / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D003483:Cutis Laxa / Q000235:genetics / Q000473:pathology*; D004547:Elastic Tissue / Q000473:pathology / Q000648:ultrastructure; D004797:Enzyme-Linked Immunosorbent Assay; D006579:Heterozygote; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D009154:Mutation; D010641:Phenotype; D010808:Physical Examination; D020641:Polymorphism, Single Nucleotide; D011561:Pseudoxanthoma Elasticum / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D014463:Ultrasonography; D014813:Vitamin K Deficiency / Q000175:diagnosis / Q000235:genetics / Q000473:pathology
chemical_list: D027425:ATP-Binding Cassette, Sub-Family C Proteins; C102029:ABCC6 protein, human