Pseudoxanthoma elasticum (PXE) is an inherited connective tissue disorder characterized histologically by fragmented elastic fibers.
Homozygous mutations in ABCC6 have been identified as causative for PXE, and characterization of these mutations has allowed clarification of the various PXE subtypes. In this case series,
Martin et al describe individuals with heterozygous ABCC6 mutations who demonstrate symptoms of PXE, suggesting a phenotype overlap between heterozygous carriers and some patients with PXE. Heterozygous individuals may rarely demonstrate the severe ophthalmologic and cardiovascular manifestations of PXE. Such heterozygous patients should be considered to have PXE by definition, and physicians should initiate appropriate clinical follow-up of heterozygous ABCC6 mutation carriers.
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The palmoplantar keratoses (PPKs) include a heterogeneous group of disorders difficult to classify because of interindividual and intraindividual variations and differences in nomenclature. Based on accepted classification schemes, the diffuse autosomal recessive hereditary PPKs include mal de Meleda, Gamborg-Nielsen type, “Nagashima type,” and acral keratoderma. Almost 20 cases of Nagashima-type PPK have been reported from Japan, but this disease remains poorly recognized elsewhere in the world. In this case report, Kabashima et al describe a 17-year-old with Nagashima-type PPK and carefully differentiate the clinical and genetic findings from those of mal de Meleda PPK.
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X-linked ectodermal dysplasia with immunodeficiency (XL-EDA-ID)
is characterized by hypohidrosis, dental anomalies, alopecia, and immunodeficiency and is associated with hypomorphic mutations in IKBKG, which codes for NEMO (nuclear factor-κB essential modulator). Male patients with NEMO mutations are difficult to diagnose in infancy. In this case report, Mancini et al describe a male infant with XL-EDA-ID whose mother reported a history of incontinentia pigmenti with mild expressivity. The authors describe the relationship of heterozygous large-scale deletions of IKBKG mutation to incontinentia pigmenti, as opposed to the hypomorphic mutations in IKBKG in which some NEMO function is preserved resulting in the XL-EDA-ID phenotype in affected males.
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Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by a generalized infection with human Betapapillomavirus species and an increased risk of squamous cell carcinomas in sun-exposed areas. In this case report, Kreuter et al describe a 37-year-old woman with primary lymphedema; depressed,
cell-mediated immunity; and persistent, generalized warts other than the EV-defining Betapapillomavirus species.
In addition, the typical histologic features of EV were missing. This combination of clinical findings was sufficiently similar to that of a 1987 report to suggest that it might be representative of a previously undescribed syndrome, distinct from EV and characterized by warts,
depressed immunity, lymphedema, and anogenital dysplasia (WILD syndrome).
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Vitiligo is an acquired disorder of patchy skin depigmentation,
several subtypes of which may be distinguished clinically. Melanocyte destruction in this disorder seems to have an autoimmune basis, and a major goal in vitiligo research remains the identification of key disease processes and pathways that might present novel therapeutic targets. In this prospective and retrospective study, Birlea et al describe a population of 51 patients with vitiligo and their close relatives from a geographically isolated and inbred community in the mountains of northern Romania in which there is a greatly elevated frequency of vitiligo. The age at onset of vitiligo is relatively delayed, suggesting that the cause of vitiligo may be somewhat atypical in this community. Genetic segregation analysis was consistent with a single major locus recessive model, although incomplete reentrance and heritability suggest that other genes and environmental factors may influence the disease phenotype.
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This Month in Archives of Dermatology. Arch Dermatol. 2008;144(3):296. doi:10.1001/archderm.144.3.296