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Stroke and Transient Ischemic Attacks of the Brain and Eye
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Pseudoxanthoma elasticum (PXE) is an inherited systemic disease of connective tissue related to mutations in the ABCC6 (adenosine triphosphate [ATP] binding cassette subtype C number 6) gene, which primarily affects the skin, retina, and cardiovascular system. It is characterized pathologically by elastic fiber mineralization and fragmentation (so-called “elastorrhexia”), large artery calcifications and stenosis, and clinically by substantial heterogeneity in age of onset and the extent and severity of organ system involvement. The diagnosis relies on clinical features and the histologic demonstration of abnormal, calcified elastic fibers in the dermis through the use of special stains.
Disorders of bone and connective tissue
Published in Angus Clarke, Alex Murray, Julian Sampson, Harper's Practical Genetic Counselling, 2019
Most cases of pseudoxanthoma elasticum follow autosomal recessive inheritance, but a few apparently dominant families have been described, mostly with milder clinical features. Asymptomatic individuals may be detected by the presence of angioid streaks in the retina. Most cases are caused by homozygous or compound heterozygous mutations in ABCC6, leading to calcification of elastic fibres in skin, the arterial wall and the retina; the apparently dominant families mostly represent examples of pseudo-dominant inheritance.
Medical retina
Published in Mostafa Khalil, Omar Kouli, The Duke Elder Exam of Ophthalmology, 2019
Pseudoxanthoma elasticum: Most common systemic association. Mutation in the ABCC6 gene. Presents with yellow papular lesions with excessive wrinkling (‘plucked chicken’ appearance) of skin usually in the neck, inguinal folds and antecubital fossa.
Pseudoxanthoma elasticum and retinitis pigmentosa: dual diagnosis of recessive conditions with ophthalmological consequences
Published in Ophthalmic Genetics, 2020
Disha Katiyar, Peter Davies, Himanshu Goel
Pseudoxanthoma elasticum (PXE) is an autosomal recessive connective tissue disease with variable systemic manifestations that are a result of mineralisation and fragmentation of elastic fibres (1). The prevalence of PXE is estimated to be between 1:25 000 and 1:100 000 (2). Pathogenic mutations in ABCC6 (OMIM 603234) are associated with PXE. ABCC6 (Chr16p13.1) encodes for multidrug resistance protein six (MRP6) which is a part of the ATP-binding cassette family (2). The highest level of ABCC6 expression is in the liver and kidney cell membranes; for this reason, it is theorised that PXE is a metabolic disease caused by abnormal levels of molecules which play a role in the synthesis of the extracellular matrix (1). Since connective tissue is present throughout the body, the disease manifests with skin, eye and cardiovascular features.
Hickam’s Dictum: Pseudoxanthoma elasticum and Usher syndrome in a single patient
Published in Ophthalmic Genetics, 2020
Kevin Wang, Brittney Statler, Michael Ramos, Meghan J DeBenedictis, Amy Babiuch, Alex Yuan, Elias I. Traboulsi
Our patient’s characteristic pseudoxanthomatous skin changes along with the presence of angioid streaks were compatible with the previously diagnosed PXE, another rare, autosomal recessive multi-system disease characterized by calcification of elastic fibers due to pathogenic variants in the ABCC6 gene. There is involvement of dermatologic, ophthalmic, and vascular systems with more than 300 different loss of function variants in ABCC6 described. The true prevalence of PXE remains unknown, but estimates range from 1 in 100 000 to 1 in 25 000 (12). Calcium deposition in Bruch’s membrane causes thickening and breaks that appear as angioid streaks on fundus exam. While angioid streaks are highly suggestive of a systemic abnormality, they are not pathognomonic for PXE. Other ocular manifestations of PXE include optic nerve head drusen, peau d’orange retinal pattern and retinal pigment epithelium (RPE) atrophy (13). RPE atrophy was observed in our patient, with multi-lobular atrophic changes radiating from the optic nerve that progressed over time (Figure 1E-H). These atrophic changes are similar to the PXE-associated, multi-lobular atrophy initially described by Sawa et al. (13).
Coquille d’oeuf in young patients affected with Pseudoxantoma elasticum
Published in Ophthalmic Genetics, 2019
Vittoria Murro, Dario Pasquale Mucciolo, Dario Giorgio, Andrea Sodi, Federica Boraldi, Daniela Quaglino, Gianni Virgili, Stanislao Rizzo
Five young PXE patients (2 males and 3 females) were investigated. Mean age was 16 years (range 12–20 years) from three different families. P2 and P3 were brother and sister whereas P4 and P5 were twins. Positive Skin biopsy was available for four patients (P1, P3, P4, P5), patient P2 did not perform the biopsy exam. Analysis of genetic features revealed that P1 was heterozygous for only one rare sequence variant in the ABCC6 gene (c.1132C>T, p.Gln378*) (9), but additional analyses on other genes that have been recently associated to Pseudoxanthoma Elasticum (i.e. GGCX and ENPP1) (10) revealed, in ENPP1, the functional polymorphism c.517A>C, p.Lys173Gln (11). The other patients were compound heterozygous for two pathogenic sequence variants in the ABCC6 gene. In particular, P2 and P3 were carriers of the stop codon variant c.3490C>T, p.Arg1164* (12) and of the splicing mutation c.3736-1G>A (13), whereas P4 and P5 were carriers of the splice site mutation c.2247 + 1G>A (14) and of the missense mutation c.3661C>T, p.Arg1221Cys (15). All patients were asymptomatic, and the visual acuity was 20/20 in both eyes. Fundus examination showed retinal abnormalities in all patients.