Recessive mutation in desmoplakin disrupts desmoplakin-intermediate filament interactions and causes dilated cardiomyopathy, woolly hair and keratoderma.

Desmosomes are major cell adhesion junctions, particularly prominent in the epidermis and cardiac tissue and are important for the rigidity and strength of the cells. The desmosome consists of several proteins, of which desmoplakin is the most abundant. Here, we describe the first recessive human mutation, 7901delG, in the desmoplakin gene which causes a generalized striate keratoderma particularly affecting the palmoplantar epidermis, woolly hair and a dilated left ventricular cardiomyopathy. A number of the patients with this syndromic disorder suffer heart failure in their teenage years, resulting in early morbidity. All tested affected members of three families from Ecuador were homozygous for this mutation which produces a premature stop codon leading to a truncated desmoplakin protein missing the C domain of the tail region. Histology of the skin revealed large intercellular spaces and clustering of desmosomes at the infrequent sites of keratinocyte adhesion. Immunohistochemistry of skin from the patients showed a perinuclear localization of keratin in suprabasal keratinocytes, suggesting a collapsed intermediate filament network. This study demonstrates the importance of desmoplakin in the attachment of intermediate filaments to the desmosome. In contrast to null DESMOPLAKIN: mice which die in early development, the truncated protein due to the homozygous 7901delG mutation in humans is not embryonic lethal. This suggests that the tail domain of desmoplakin is not required for establishing tissue architecture during development.

Epidermolytic palmoplantar keratoderma with woolly hair and dilated cardiomyopathy.

BACKGROUND: A new cardiocutaneous syndrome has been noted, characterized by an epidermolytic palmoplantar keratoderma and woolly hair, and associated with dilated cardiomyopathy. OBJECTIVE: This describes the clinical and histopathologic characteristics of this new syndrome. METHODS: Eighteen patients were examined clinically and histologically from 1970 to 1997. Cardiologic examinations were performed in 12 patients. The cutaneous lesions were classified according to the presence of obligatory and facultative elements of the syndrome. RESULTS: Patients were born with woolly hair. Around the first year palmoplantar keratoderma and the other keratotic elements appeared. The first cardiac abnormalities are exclusively electrocardiographic and occur in asymptomatic patients. In these patients, dilation of the left ventricle together with alterations in muscle contractility are observed. The dilated cardiomyopathy can lead to congestive heart failure and death. CONCLUSION: The association of woolly hair and palmoplantar keratoderma with a histopathologic pattern of epidermolytic hyperkeratosis has not been previously described. Their frequent association with dilated cardiomyopathy defines a cardiocutaneous syndrome. Whenever woolly hair is associated with any kind of palmoplantar keratoderma, a search for possible cardiac abnormalities is recommended.

[The amyloidoses]. / Las amiloidosis.

There are many clinical types of amyloidosis, as many as chemical types of amyloid substance would be its substratum. This clinic-chemical plurality permits us to talk about the amyloidosis. This article is specially guided to those amyloidosis that present cutaneous damages during its clinical course. They are the immunocytic amyloidosis and the keratinocytic amyloidosis.

[Ashy dermatitis. Comments on 2 clinical forms]. / Dermatitis cenicienta. Apreciaciones sobre dos formas clínicas.

The typical clinical characteristic of the ashy dermatitis is the fact that in case of light colored skin, the grey colour remains invariable. There is a new clinical form which is called the Brown Cinder Dermatitis which is characterized by a disciplined localization in the center of the face, trunk or upper extremities together with an inexorable change of the grey colour at the beginning to a brown colour at the end on the other it, has be enhanced the existence of the nummular form which is characterized by the existence of many greyish independent spots of circular or oval form mainly at the level of the trunk.

[Robles' disease (onchocerciasis). Presentation of the first confirmed case in Ecuador]. / Enfermedad de Robles (oncocercosis). Presentación del primer caso comprobado en Ecuador.

For the first time a case of "onchocercosis " was found in Ecuador. The patient is a coloured person which was examined in the Dermatology Department of the "Luis Vernaza" Hospital. The diagnosis was established on the bases of a biopsy of a thoracic nodule. The principal lesions which were established are the following: intense and generalized pigmentation of violet tones; a very accentuated ictiosiform statey specially on the trunk; hardened accematous plaques in the fore-arms; eruptions on the buttocks nodules in the region of the iliac bone and zones of vitiligo on the anterior part of the legs; linfatic nodules were also observed. Elefantiasis of the penis and scrotum. With this case we have established an endemic focus of onchocercosis in Esmeraldas, Ecuador.

[Larva migrans syndrome. Migratory hypodermitis]. / Síndrome de larva migrans. Hipodermitis migratorias.

The larva migrans syndrome is superficial and deep. Superficial when it acts at the epidermis level and deep when the larva produces a hipodermic reaction. In the latter, are included the hypodermitis of the paragonimiasis and of the gnathostomiasis, subjects that have been discussed thoroughly in this paper.