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Consequences of This Phenotype Overlap for the Definition of PXE

Ludovic Martin, MD, PhD; Frédéric Maître, MD; Pierre Bonicel, MD; Patrick Daudon, MD; Christophe Verny, MD, PhD; Dominique Bonneau, MD, PhD; Olivier Le Saux, PhD; Nicolas Chassaing, MD

Arch Dermatol. 2008;144(3):301-306.

Objectives  To illustrate a phenotypic overlap consisting of usual, but limited, or atypical manifestations of pseudoxanthoma elasticum (PXE) between heterozygous carriers of a single ABCC6 mutation and patients diagnosed with PXE, carriers of homozygous or compound heterozygous mutations.

Design  Evaluation for full and typical, incomplete, mild, or overlooked PXE during a 5-year period (2001-2005) based on the following 1992 expert consensus conference items: (1) yellowish papular skin eruption, (2) dermal elastorrhexis and mineralization of elastic fibers in lesional skin, and (3) angioid streaks. Testing for ABCC6 mutations was performed in all cases after informed consent.

Setting  French multidisciplinary outpatient clinic for patients with PXE.

Participants  Patients prospectively referred for PXE and first-degree relatives.

Main Outcome Measure  Prevalence of PXE with a limited or atypical phenotype and manifesting heterozygosity.

Results  Ninety-four patients were diagnosed as having PXE. Fifty-eight relatives were also examined, and none displayed the characteristic signs of the disease. Despite the histoclinical items and ABCC6 genotyping, we were unable to establish a definite diagnosis in 5 additional referred cases, ie, to distinguish between PXE with a limited or atypical phenotype and heterozygosity with skin and/or ophthalmologic and/or cardiovascular manifestations suggestive of PXE.

Conclusions  We assume that all categories established at the 1992 consensus conference correspond to PXE, but that the 5 patients reported herein also have PXE. Homozygous, compound heterozygous, or heterozygous individuals may fulfill only some of the clinical and/or histopathologic consensus criteria of PXE. They cannot be placed into any category. Expressivity is highly variable in carriers of 1 or 2 ABCC6 mutations, and the disease manifestations overlap between both genotypes. Physicians should thus be more cautious with respect to the prognosis when faced with heterozygous relatives of a patient diagnosed with undisputable PXE. Indeed, heterozygotes may uncommonly experience severe ophthalmologic complications. Whether they may also have cardiovascular complications related to or worsened by PXE remains to be determined.

Author Affiliations: Department of Dermatology and PXE Consultation Center, Orléans Hospital, Orléans, France (Drs Martin, Maître, Bonicel, and Daudon); Departments of Neurology (Dr Verny) and Medical Genetics and INSERM U694 (Dr Bonneau), University Hospital, Angers, France; John A. Burns School of Medicine, University of Hawaii, Honolulu (Dr Le Saux); and INSERM U563, "centre de physiopathologie," and Department of Medical Genetics, Purpan University Hospital, Toulouse, France (Dr Chassaing).

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