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.