Hanging on by a thread: a rare case of secondary pseudoainhum.

Pseudoainhum is a rare and poorly characterised phenomenon involving autoamputation of a digit associated with an identifiable or related disease process. We describe the case of a 19-year-old man with long-standing neurodisability, sensorineural hearing loss and severe keratoderma, presenting with painless rapidly-progressing autoamputation of his left little toe. Genetic analysis thus far has been inconclusive. The toe appeared to be hanging on by a thread, with no clinical signs of infection. Radiographs showed lysis with complete resorption of the proximal phalynx. Routine blood tests found an isolated neutropenia with normal C reactive protein and biochemistry. We report an unusual case of a young adult with a history of chronic neurological and dermatological problems presenting with secondary pseudoainhum and provide a valuable addition to the limited literature describing this rare condition.

Suppressing AP1 factor signaling in the suprabasal epidermis produces a keratoderma phenotype.

Keratodermas comprise a heterogeneous group of highly debilitating and painful disorders characterized by thickening of the skin with marked hyperkeratosis. Some of these diseases are caused by genetic mutation, whereas other forms are acquired in response to environmental factors. Our understanding of signaling changes that underlie these diseases is limited. In the present study, we describe a keratoderma phenotype in mice in response to suprabasal epidermis-specific inhibition of activator protein 1 transcription factor signaling. These mice develop a severe phenotype characterized by hyperplasia, hyperkeratosis, parakeratosis, and impaired epidermal barrier function. The skin is scaled, constricting bands encircle the tail and digits, the footpads are thickened and scaled, and loricrin staining is markedly reduced in the cornified layers and increased in the nucleus. Features of this phenotype, including nuclear loricrin localization and pseudoainhum (autoamputation), are characteristic of the Vohwinkel syndrome. We confirm that the phenotype develops in a loricrin-null genetic background, indicating that suppressed suprabasal AP1 factor function is sufficient to drive this disease. We also show that the phenotype regresses when suprabasal AP1 factor signaling is restored. Our findings suggest that suppression of AP1 factor signaling in the suprabasal epidermis is a key event in the pathogenesis of keratoderma.

No exonic mutations at GJB2, GJB3, GJB4, GJB6, ARS (Component B), and LOR genes responsible for a Chinese patient affected by progressive symmetric erythrokeratodermia with pseudoainhum.

OBJECTIVE: Progressive symmetric erythrokeratodermia (PSEK) is characterized by symmetric and growing erythematous hyperkeratotic patches over the body shortly after birth, particularly trunk and limbs, the buttocks, and the face, sometimes together with palmoplantar keratoderma (PPK). The GJB2, GJB3, GJB4, GJB6, ARS (Component B), and LOR gene mutation might contribute to PSEK manifestation. This study aimed to identify sequence alteration of these genes in a Chinese PSEK patient with pseudoainhum. METHODS: Genomic DNA was purified from the patient's peripheral blood. Mutation analysis of target genes was performed by direct sequencing using ABI 3730 sequencer RESULTS: No exonic mutations was identified in the aforementioned genes. CONCLUSIONS: The result underlines the genetic heterogeneity of PSEK and other related erythrokeratodermas.

Palmoplantar keratoderma, pseudo-ainhum, and universal atrichia: A new patient and review of the palmoplantar keratoderma-congenital alopecia syndrome.

Palmoplantar keratoderma (PPK) may concur with congenital alopecia (CA) in various genodermatoses. We report on a 10-year-old girl with generalized atrichia and a severe form of PPK causing pseudo-ainhum, sclerodactyly, and contractures, a phenotype not consistent with any well-defined condition. Non-specific additional findings comprised mild nail dystrophy and widespread keratosis pilaris including ulerythema ophryogenes. Direct sequencing of the GJB2 and LOR coding regions yielded normal results. A review identified two additional sporadic and four familial cases with PPK and CA. Comparison between familial cases suggested the existence of two genetically and phenotypically distinct types of PPK-CA: (i) an autosomal dominant form (Stevanovic type), a variable and benign phenotype without significant hand complications, and (ii) a more complex autosomal recessive variant (Wallis type) with contractures, sclerodactyly, and pseudo-ainhum. Nuclear cataract may represent an additional although not constant finding in the Wallis type PPK-CA. Further reports are required to test this preliminary conclusion.

Novel mutation p.Gly59Arg in GJB6 encoding connexin 30 underlies palmoplantar keratoderma with pseudoainhum, knuckle pads and hearing loss.

BACKGROUND: Connexins, components of the gap junction, are expressed in several organs including the skin and the cochlea. Mutations in connexin genes including GJB2 (Cx26), GJB3 (Cx31), GJB4 (Cx30.3), GJB6 (Cx30) and GJA1 (Cx43) are responsible for various dermatological syndromes and/or inherited hearing loss, frequently showing overlapping phenotypes. OBJECTIVES: To clarify the spectrum of clinical phenotypes caused by connexin mutations. METHODS: We report a 32-year-old Japanese woman with mild palmoplantar keratoderma (PPK) with severe sensorineural hearing loss, knuckle pads and pseudoainhum of her toes. RESULTS: Direct sequencing revealed no mutation in GJB2, but a novel heterozygous missense mutation p.Gly59Arg in GJB6. Electron microscopy revealed no apparent morphological abnormality of gap junctions in the patient's lesional epidermis. CONCLUSIONS: The patient harboured the novel GJB6 missense mutation p.Gly59Arg in the first extracellular loop of Cx30. Mutations in glycine 59 of Cx26 are associated with PPK-deafness syndrome, and the similar phenotype here supports the observed heteromeric channel formation; the dominant nature of the mutation suggests an effect on gap junctions similar to that of the comparable mutation in Cx26.

Genodermatoses.

This article describes some of the genodermatoses encountered in the black populations in Africa, starting with ainhum, which appears to be genetically determined. Palmoplantar keratodermas are common in Africa but are difficult to classify and their hereditary nature is not always recognized. Of the ichthyoses, the lamellar type is commonest, with the so-called bathing-suit distribution apparently unique to Africans. Albinism and xeroderma pigmentosum are important causes of cutaneous malignancy in the tropics. Neurofibromatosis and tuberous sclerosis are relatively common, whereas hypermelanosis of Ito is rare but easy to recognize in dark skin.

[Pseudo-ainhum in Vohwinkel disease. Keratoma hereditarium mutilans]. / Pseudo-Ainhum bei Morbus Vohwinkel. Keratoma hereditarium mutilans.

An 11-year-old Turkish boy who has suffered from palmoplantar keratosis since his first year of life is presented. He is the only one of a large family to be affected. The diffuse keratosis extends to the back of the hands and feet and still has a progressive course. At the age of 6 he developed a symmetric high-tone acoustic impairment and at 10, an ainhum-like constricting band around the fifth digit of the left hand. This constellation of symptoms is highly characteristic for mutilating keratoma (Vohwinkel's disease), which is a rare disorder of keratinization. The majority of cases in the literature have had an autosomal dominant pattern of inheritance, although sporadic cases like this have also been reported as well. If constricting band proceeds to the point where spontaneous amputation seems imminent, a therapy with orally administered retinoids should be considered.

Dactylolisis criptogenética familiar: presentación de un caso / Failial cryptogenetic dactylolysis: report of a case

Se presenta un caso de dactylolisis criptogenética familiar. Se analiza su incidencia en edad, sexo y raza y se exponen las distintas teorías actuales de su etiología. Se describen sus aspectos histológicos, así como el cuadro clínico en esta entidad. Se realiza un estudio del diagnóstico positivo y diferencial. Se esboza el tratamiento que se siguió en nuestro caso, así como los resultados del mismo (AU)

Dactylolisis criptogenética familiar: presentación de un caso / Familial cryptogenetic dactylolysis: report of a case

Se presenta un caso de dactylolisis criptogenética familiar. Se analiza su incidencia en edad, sexo y raza y se exponen las distintas teorías actuales de su etiología. Se describen sus aspectos histológicos, así como el cuadro clínico en esta entidad. Se realiza un estudio del diagnóstico positivo y diferencial. Se esboza el tratamiento que se siguió en nuestro caso, así como los resultados del mismo