| An 64-year-old woman had pseudoxanthoma elasticum (PXE) with the characteristic skin and oculair findings. She had no associated systemic systems and no family history of PXE. The case-report is reviewed with regard to etiology, clinical features, diagnosis, inheritance and, particularly, management. ( info) |
| A 26-year-old woman collapsed and died suddenly while dancing. autopsy findings included the cutaneous lesions of pseudoxanthoma elasticum (PXE), a rare genetic disease with autosomal dominant and recessive inheritance patterns. Pathologic findings of PXE (degenerated elastic fibers) were seen in the stenotic epicardial coronary arteries, the intramyocardial arterioles, the subendocardium, the mitral valve, and the blood vessels of other viscera. The mitral valve was slightly myxoid. Intramyocardial arteriolar involvement has not been previously described in PXE. The other cardiac findings have only been described in a few cases. Although mitral valve prolapse in PXE has been shown echocardiographically, it is unclear whether or not the mitral valve findings in this case represent the substrate for this condition. It is important that autopsy pathologists search carefully for the pathognomonic skin lesions of PXE in cases of sudden death associated with coronary disease, mitral valve prolapse, or endocardial lesions. Recognition of this disease is essential for proper genetic counseling of surviving family members. ( info) |
13/151. Preclinical diagnosis of pseudoxanthoma elasticum - methodological restrictions and ethical problems. pseudoxanthoma elasticum (PXE) is an inherited connective tissue disease. Only recently, mutations in the MRP6 gene on chromosome 16p13.1 have been identified in PXE families. Up to now, predictive testing has not been available. Since ultrastructural connective tissue alterations in overtly normal skin of predilection sites have supported preclinical diagnosis in children of affected individuals, we have screened the daughters of a PXE patient for these alterations. The patient's biopsy from lesional skin revealed elastin and collagen fibril abnormalities, but biopsies from the clinically inconspicuous daughters showed only ultrastructural alterations of collagen fibrils. These findings are inconclusive regarding the diagnosis of PXE in the daughters. Predictive or preclinical diagnosis of incurable, late-onset disorders creates complex social, ethical, and legal problems which call for special management strategies. ( info) |
14/151. Acute aortic valvular regurgitation secondary to avulsion of aortic valve commissure in a patient with pseudoxanthoma elasticum. A 68-year-old woman developed acute pulmonary edema due to severe acute aortic valvular regurgitation. At the time of emergency surgery, it turned out to result from spontaneous avulsion of the aortic valve commissure. Later, the patient was diagnosed to have pseudoxanthoma elasticum based on typical skin lesions. connective tissue abnormalities associated with pseudoxanthoma elasticum might have contributed to the development of the avulsion of the aortic valve in this particular patient. ( info) |
15/151. Compound heterozygosity for a recurrent 16.5-kb Alu-mediated deletion mutation and single-base-pair substitutions in the ABCC6 gene results in pseudoxanthoma elasticum. pseudoxanthoma elasticum (PXE) is a systemic heritable disorder affecting the elastic structures in the skin, eyes, and cardiovascular system, with considerable morbidity and mortality. Recently, mutations in the ABCC6 gene (also referred to as "MRP6" or "eMOAT") encoding multidrug-resistance protein 6 (MRP6), a putative transmembrane ABC transporter protein of unknown function, have been disclosed. Most of the genetic lesions delineated thus far consist of single-base-pair substitutions resulting in nonsense, missense, or splice-site mutations. In this study, we examined four multiplex families with PXE inherited in an autosomal recessive pattern. In each family, the proband was a compound heterozygote for a single-base-pair-substitution mutation and a novel, approximately 16.5-kb deletion mutation spanning the site of the single-base-pair substitution in trans. The deletion mutation was shown to extend from intron 22 to intron 29, resulting in out-of-frame deletion of 1,213 nucleotides from the corresponding mRNA and causing elimination of 505 amino acids from the MRP6 polypeptide. The deletion breakpoints were precisely the same in all four families, which were of different ethnic backgrounds, and haplotype analysis by 13 microsatellite markers suggested that the deletion had occurred independently. Deletion breakpoints within introns 22 and 29 were embedded within AluSx repeat sequences, specifically in a 16-bp segment of dna, suggesting Alu-mediated homologous recombination as a mechanism. ( info) |
16/151. pseudoxanthoma elasticum: significance of limited phenotypic expression in parents of affected offspring. The inheritance pattern of pseudoxanthoma elasticum (PXE) is controversial. inheritance patterns are confounded by delayed diagnosis and mild or limited phenotypic expression among certain family members. Because testing for the genetic mutation(s) responsible for PXE is not routine, genetic counseling must be done with caution. We describe 4 families in which one or more children were diagnosed with PXE. Detailed examination of the parents was carried out, including skin biopsy and ophthalmologic examination. In 3 of the 4 families, one parent had limited phenotypic expression, such as ocular findings without skin lesions or very mild skin lesions with no ocular findings. In the other family, one parent had very mild skin and ocular disease. All 4 affected parents had diagnostic skin biopsy findings. In none of the 4 families was the inheritance pattern clear-cut. Although the inheritance pattern of PXE has been debated, clinically significant stigmata of PXE, which are not always readily apparent, can occur in successive generations. Therefore all first-degree relatives of affected patients should receive a full dermatologic examination as well as a funduscopic examination. If even mild typical skin or eye findings are present, then skin biopsy should be performed. ( info) |
| BACKGROUND: pseudoxanthoma elasticum (PXE) is a rare hereditary disease characterised by systemic degeneration of elastic tissue. Calcification of elastic fibres seen histologically is pathognomonic for the disorder. Most pseudoxanthoma elasticum patients show no serious complications during pregnancy. CASE: We report a case of a 29-year-old white woman with pseudoxanthoma elasticum, who delivered a healthy infant at the 35th week by cesarean section after an uneventful pregnancy. Sonographic and histological placental findings are described. CONCLUSION: pregnancy in a patient with pseudoxanthoma elasticum presents some problems such as the evolution of the disease in the soon to be mother and the influence of the disease on the pregnancy. In our case there were no fetal-maternal complications related to the disease except skin lesion aggravation. ( info) |
| PURPOSE: To report a case of visual improvement after macular translocation performed for a subfoveal choroidal neovascular membrane in a patient with pseudoxanthoma elasticum and angioid streaks. methods: The fovea was translocated inferiorly by scleral imbrication, intentional retinal detachment with a small posterior retinotomy, and partial fluid-air exchange. The choroidal neovascular membrane was photocoagulated 1 week later. RESULTS: The visual acuity of the patient improved from 20/125 to 20/40. The center of the foveal avascular zone was moved inferiorly 844 microm. The choroidal neovascular membrane was extrafoveal after translocation and was treated with laser photocoagulation. CONCLUSION: Macular translocation may be considered in the management of subfoveal choroidal neovascular membrane in patients with pseudoxanthoma elasticum and angioid streaks. ( info) |
19/151. pseudoxanthoma elasticum: Point mutations in the ABCC6 gene and a large deletion including also ABCC1 and MYH11. pseudoxanthoma elasticum (PXE) is a mendelian disorder characterized by calcification of elastic fibers in skin, arteries, and retina. It results in dermal lesions, arterial insufficiency and retinal hemorrhages, leading to macular degeneration. PXE is transmitted either as an autosomal dominant or recessive trait and several sporadic cases have been observed. Mutations in the ABCC6 gene have been identified very recently in patients. Here, we report on a large Italian family affected by pseudoxanthoma elasticum for which linkage analysis had pointed to a region encompassing markers D16S3069-D16S405-D16S3103; hemizygosity of marker D16S405 allowed us to detect a submicroscopic deletion of at least 900 kb involving ABCC6, ABCC1, and MYH11. mutation analysis on the other allele of the family, as well as on two additional sporadic cases, revealed nonsense (Y227X, R518X, R1164X) and frame-shift (c.960delC) mutations in ABCC6 (MRP6) further confirming the role of this multi-drug resistance gene in the etiology of pseudoxanthoma elasticum. Furthermore, clinical re-examination of members of the family harboring the deletion led to the detection of additional features, potentially caused by the deletion of the MYH11 gene. In the course of the analysis five nonpathogenic variants were found in ABCC6: 1233T>C, 1245G>A, 1838 T>G (V614A), 1890C>G, and 3506 83C>A. Hum Mutat 18:85, 2001. ( info) |
20/151. pseudoxanthoma elasticum diagnosed 25 years after the onset of cardiovascular disease. A 63-year-old man who had experienced cerebral infarction and myocardial infarction at an early age, and repeatedly underwent coronary angioplasty was admitted to our hospital for cardiac evaluation. A coronary angiography showed complex multi-vessel disease with significant stenosis in all major vessels and coronary-artery bypass grafts. A funduscopic examination to evaluate hypertensive and diabetic changes revealed angioid streaks. Therefore, a skin biopsy was performed despite the absence of characteristic skin lesions. Histopathologic examinations revealed calcification and fragmentation of elastic fibers. Therefore, he was finally diagnosed as having pseudoxanthoma elasticum 25 years after the onset of cardiovascular disease. ( info) |