ABSTRACT
Desmosomes are intercellular adhesive junctions and attachment sites for the intermediate filament (IF) cytoskeleton, prominent in tissues subject to high levels of mechanical stress such as the epidermis and heart. The obligate desmosomal constituent, plakoglobin (PG), is involved in coupling transmembrane desmosomal components with IFs. PG also contributes to intercellular adhesion through adherens junctions and has additional signaling roles. To date, two mutations in the gene encoding PG, JUP, have been described, and in both instances, patients harboring pathogenic mutations suffered from arrhythmogenic right ventricular cardiomyopathy with or without skin abnormalities. We describe homozygous nonsense mutation, p.S24X, and homozygous splice site mutation, c.468G>A, in the JUP gene that results in skin fragility, diffuse palmoplantar keratoderma, and woolly hair with no symptoms of cardiomyopathy. We show barely detectable levels of PG immunostaining in skin sections from patients harboring these mutations and show that an alternative AUG codon in p.S24X mRNA translates a 42-amino-acid N-terminal truncation. We conclude that PG is required for correct maintenance of skin integrity, and the absence of heart phenotype in patients suggests that aberrant PG expression does not compromise normal human heart development in children. Our findings provide new insight into the distinct roles that PG has in the epidermis and heart.
Subject(s)
Cardiomyopathies/genetics , Codon, Nonsense/genetics , Desmoplakins/genetics , Heart/growth & development , Homozygote , RNA Splice Sites/genetics , Skin Diseases, Genetic/genetics , Biopsy , Cardiomyopathies/physiopathology , Child , Child, Preschool , DNA, Complementary/genetics , Desmoplakins/physiology , Female , Heart/physiology , Humans , Infant , Male , Nucleic Acid Amplification Techniques , Phenotype , Polymorphism, Single Nucleotide/genetics , RNA, Messenger/genetics , Skin/pathology , Skin/ultrastructure , Skin Diseases, Genetic/physiopathology , gamma CateninABSTRACT
An 8-year-old mentally retarded boy had paired segmental areas of hyper- and hypopigmentation on the left side of his body in association with cutis marmorata telangiectatica congenita (CMTC) involving the trunk and the limbs, with the exception of parts of his right arm. At the age of 4 years, an aneurysmatic nodular lesion developed in the angle of his right elbow, and subsequently two similar lesions emerged on his forehead and scalp. Moreover, a dysmorphic facial appearance, scoliosis, genu valgum, talipes planus and increased laxity of joints were noted. The coexistence of paired achromic and melanotic macules in the form of "cutis tricolor" with CMTC can be categorized as an unusual example of phacomatosis pigmentovascularis (PPV). This combination differs from all other types of PPV so far known, which is why we propose the new term "phacomatosis achromico-melano-marmorata". Future clinical research may show whether analogous "simple" twin-spot phenotypes in the form of "phacomatosis melanomarmorata" or "phacomatosis achromicomarmorata" do likewise exist.
Subject(s)
Hyperpigmentation , Hypopigmentation , Intellectual Disability , Neurocutaneous Syndromes/diagnosis , Child , Humans , Male , SyndromeABSTRACT
This is a follow-up report on a boy with phacomatosis pigmentokeratotica. At the age of 10 years he had, in addition to a sebaceous nevus and a speckled lentiginous nevus, multiple lesions of a collagen nevus localized on the chin and in the lumbar area. On the left shoulder, a small telangiectatic spot was present within the area of the speckled lentiginous nevus. Moreover, hemiatrophy of the left-hand side of the body and hyperhidrosis of the left lumbar area were noted. At the age of 16, the lesions of his collagen nevus had considerably enlarged and showed an arrangement along Blaschko lines. Additional pinhead-sized vascular lesions were noted, with preponderance within the area of the speckled lentiginous nevus in the left scapular region and on his left leg. Moreover, the boy had developed severe arterial hypertension since the age of 13. Angiographic examination showed an aortic stenosis that reached from the aortic arch down to the origin of the renal arteries, necessitating a surgical intervention. From this follow-up report we conclude that phacomatosis pigmentokeratotica may be associated with other cutaneous abnormalities such as linear connective tissue nevus of the collagen type and multiple pinhead-sized angioma-like lesions superimposed on the speckled lentiginous nevus. The associated defects of the large vessels may belong to the component of Schimmelpenning syndrome representing one "half" of phacomatosis pigmentokeratotica, rather than being part of the speckled lentiginous syndrome that forms the other "half" of this twin-spot phenotype.
Subject(s)
Aortic Valve Stenosis/diagnostic imaging , Melanosis/diagnosis , Neurocutaneous Syndromes/diagnosis , Vascular Malformations/diagnostic imaging , Adolescent , Angiography , Aortic Valve Stenosis/physiopathology , Disease Progression , Follow-Up Studies , Humans , Male , Melanocytes/pathology , Melanosis/pathology , Neurocutaneous Syndromes/pathology , Severity of Illness Index , Vascular Malformations/physiopathologyABSTRACT
We followed over 10 years three girls with focal dermal hypoplasia syndrome. The histopathological changes demonstrated at the optical level an hypoplastic dermis with thin and scarce collagen bundles and a marked diminution of elastic fibers. Mature adipose tissue was found scattered within the papillary and reticular dermis. No alterations in the basal membrane were observed by immunocytochemical or ultrastructural techniques. Ultrastructurally, in the skin-affected areas, loosely arranged collagen bundles composed of few fibrils were seen scattered in the extracellular matrix. Scarce elastic fibers of normal morphology were also observed. Fibroblasts were smaller, oval-shaped, and diminished in number with a poorly developed cytoplasm. In these fibroblasts, the most conspicuous feature was a remarkable and irregular thickening of the nuclear fibrous lamina. Taking into account that a common link between all laminopaties may be a failure of stem cells to regenerate mesenchymal tissue, this failure would induce the dermal hypoplasia observed in our patients presenting Goltz syndrome.
Subject(s)
Connective Tissue/ultrastructure , Focal Dermal Hypoplasia/ultrastructure , Adipocytes/metabolism , Adipocytes/ultrastructure , Adolescent , Biomarkers/metabolism , Child , Collagen/metabolism , Collagen/ultrastructure , Connective Tissue/metabolism , Elastic Tissue/metabolism , Elastic Tissue/ultrastructure , Extracellular Matrix/metabolism , Extracellular Matrix/ultrastructure , Female , Fibroblasts/metabolism , Fibroblasts/ultrastructure , Focal Dermal Hypoplasia/metabolism , Humans , Immunoenzyme Techniques , Microscopy, Electron, Transmission , Periodic Acid-Schiff ReactionABSTRACT
We report a family in which geroderma osteodysplastica affected two male siblings. They showed the characteristic features associated with this syndrome: a prematurely aged face with wrinkly, lax skin, more prominent on the acral regions, associated with joint laxity, osteoporosis, and skeletal abnormalities. The main histologic abnormalities were fragmented elastic fibers that were diminished in number. Although collagen fibers showed changes in their orientation, they were normal in structure and number. We consider the differential diagnosis with other syndromes associated with cutis laxa using clinical, radiologic, and histopathologic criteria.
Subject(s)
Bone Diseases, Metabolic/genetics , Bone Diseases, Metabolic/pathology , Cutis Laxa/genetics , Cutis Laxa/pathology , Child , Child, Preschool , Diagnosis, Differential , Female , Humans , Male , Pedigree , SyndromeABSTRACT
Desmoplastic hairless hypopigmented nevus (DHHN) is the name Ruiz-Maldonado et al. gave to a new variant of giant congenital melanocytic nevus characterized clinically by a hard ligneous consistency, absence of hair and progressive loss of pigment. Histologically, dermal fibrosis consistent with desmoplasia is a predominant feature. We describe a 6-year-old boy with a hard hairless pigmented congenital nevus involving the lumbosacral area, buttocks, perineum and scrotum. During the first years of life, the nevus showed a progressive reduction in colour, size and consistency. These changes continued until the age of four when a well-demarcated tumour appeared, within the nevus, on the right buttock. Resection of this outgrowth was performed. Histologically, nevus cells of normal appearance between thick collagen bundles were present. Immunostaining revealed S100 +, Vim +, HMB45--results. The nevus has continued to involute to date. An immune response against the melanocytes of the nevus may explain this type of evolution.
Subject(s)
Nevus, Pigmented/pathology , Skin Neoplasms/pathology , Child , Humans , MaleABSTRACT
Two siblings with familial cutaneous collagenoma syndrome had the essential clinical features of multiple skin-colored nodules on the trunk and upper arms. On light microscopy, histopathologic findings included excessive accumulation of dense, coarse collagen in the dermis. Elastic tissue stains demonstrated a proportionately diminished number of abnormal elastic fibers intermingled with the collagen bundles. A predominance of densely packed collagen bundles of normal morphology with a marked decrease in abnormal elastic tissue were the major ultrastructural features. The diagnosis was therefore confirmed to be connective tissue nevi of the collagen type. The differential diagnosis of connective tissue nevi disorders is delineated.
Subject(s)
Connective Tissue Diseases/pathology , Skin Diseases/pathology , Child , Connective Tissue Diseases/genetics , Diagnosis, Differential , Hamartoma/pathology , Humans , MaleABSTRACT
The coexistence of linear porokeratosis (LP) and disseminated superficial actinic porokeratosis (DSAP) in a 3-year-old girl with a family history of DSAP is presented. Happle proposed loss of heterozygosity (LOH) to explain the origin of this unusual phenomenon. Homozygosity would explain why lesions in LP are far more pronounced than those of the associated heterozygous DSAP lesions. LOH would also explain the early age of presentation of the linear lesions, the family history of DSAP, and why LP cases are particularly prone to malignant transformation. This case is also important for molecular studies because of the presence of heterozygous and homozygous mutated cells in the same patient and the familial occurrence of the heterozygous form of the disease.
Subject(s)
Genetic Predisposition to Disease , Loss of Heterozygosity , Porokeratosis/diagnosis , Child, Preschool , Diagnosis, Differential , Female , Humans , Porokeratosis/complications , Porokeratosis/genetics , Porokeratosis/pathologyABSTRACT
Se presentan cuatro casos de cutis verticis gyrata (CVG), dos son individuos adultos, con cuadros correspondientes a formas primarias de la enfermedad, y dos pediátricos, que por su etiología se clasifican entre las formas secundarias. Se comentan las consideraciones clínicas y de laboratorio, así como las posibles implicaciones etiológicas y de pronóstico de cada caso (AU)
Subject(s)
Humans , Male , Adult , Female , Child , Scalp , Skin Diseases , Scalp Dermatoses , Paraneoplastic SyndromesABSTRACT
Se presentan cuatro casos de cutis verticis gyrata (CVG), dos son individuos adultos, con cuadros correspondientes a formas primarias de la enfermedad, y dos pediátricos, que por su etiología se clasifican entre las formas secundarias. Se comentan las consideraciones clínicas y de laboratorio, así como las posibles implicaciones etiológicas y de pronóstico de cada caso
Subject(s)
Humans , Male , Adult , Female , Child , Scalp , Scalp Dermatoses , Skin Diseases , Paraneoplastic SyndromesABSTRACT
Niña de 10 años de edad, de raza indo-americana, con placas verrugosas orales de siete meses de evolución. El diagnóstico clínico de hiperplasia epitelial focal fue confirmado por microscopía electrónica. Se realiza la descripción de esta patología frecuente en comunidades indígenas de bajo nivel socioeconómico y su diagnóstico diferencial con otras patologías orales clínicamente similares (AU)
Subject(s)
Humans , Female , Focal Epithelial Hyperplasia/diagnosis , Focal Epithelial Hyperplasia/pathology , Focal Epithelial Hyperplasia/therapy , Dry Ice/therapeutic useABSTRACT
Niña de 10 años de edad, de raza indo-americana, con placas verrugosas orales de siete meses de evolución. El diagnóstico clínico de hiperplasia epitelial focal fue confirmado por microscopía electrónica. Se realiza la descripción de esta patología frecuente en comunidades indígenas de bajo nivel socioeconómico y su diagnóstico diferencial con otras patologías orales clínicamente similares
Subject(s)
Humans , Female , Focal Epithelial Hyperplasia/diagnosis , Dry Ice/therapeutic use , Focal Epithelial Hyperplasia/pathology , Focal Epithelial Hyperplasia/therapyABSTRACT
La pustulosis neonatal por Malassezia furfur es una erupción papulopustulosa no folicular de cara, cuero cabelludo y cuello que aparece en el primer mes de vida. Se presentan cuatro neonatos con lesiones clínicas de pustulosis por Malassezia furfur en los cuales se confirmó el diagnóstico por examen micológico directo del material obtenido de pústulas. Se realiza diagnóstico diferencial con otras pustulosis del recién nacido, particularmente con el acné neonatal. Se observó buena respuesta terapéutica al ketoconazol tópico en forma de crema al 2 por ciento, aplicada dos veces al día durante dos semanas (AU)
Subject(s)
Humans , Male , Female , Infant, Newborn , Tinea Versicolor/complications , Malassezia/drug effects , Tinea Versicolor/diagnosis , Tinea Versicolor/drug therapy , Ketoconazole/therapeutic use , Malassezia/isolation & purification , Malassezia/pathogenicityABSTRACT
La pustulosis neonatal por Malassezia furfur es una erupción papulopustulosa no folicular de cara, cuero cabelludo y cuello que aparece en el primer mes de vida. Se presentan cuatro neonatos con lesiones clínicas de pustulosis por Malassezia furfur en los cuales se confirmó el diagnóstico por examen micológico directo del material obtenido de pústulas. Se realiza diagnóstico diferencial con otras pustulosis del recién nacido, particularmente con el acné neonatal. Se observó buena respuesta terapéutica al ketoconazol tópico en forma de crema al 2 por ciento, aplicada dos veces al día durante dos semanas
Subject(s)
Humans , Male , Female , Infant, Newborn , Malassezia/drug effects , Tinea Versicolor/complications , Ketoconazole/therapeutic use , Malassezia/isolation & purification , Malassezia/pathogenicity , Tinea Versicolor/diagnosis , Tinea Versicolor/drug therapyABSTRACT
La paquidermodactilia (PDD) es una forma rara de fibromatosis superficial benigna de los dedos de la mano, que afecta a hombres jóvenes, caracterizada por engrosamiento fusiforme de tejidos blandos de las superficies dorsal y principalmente lateral de las articulaciones interfalángicas proximales de los dedos de las manos. El objetivo de este trabajo es presentar el estudio clínico e histopatológico de una niña con paquidermodactilia asociada a porfiria cutánea tarda (PCT). Según la bibliografía consultada, dicha asociación no ha sido previamente reportada (AU)
Subject(s)
Humans , Female , Fingers/pathology , Fibroma/diagnosis , Porphyria Cutanea Tarda/complications , Fibroma/complications , Fibroma/physiopathology , Keratoderma, Palmoplantar/diagnosisABSTRACT
La paquidermodactilia (PDD) es una forma rara de fibromatosis superficial benigna de los dedos de la mano, que afecta a hombres jóvenes, caracterizada por engrosamiento fusiforme de tejidos blandos de las superficies dorsal y principalmente lateral de las articulaciones interfalángicas proximales de los dedos de las manos. El objetivo de este trabajo es presentar el estudio clínico e histopatológico de una niña con paquidermodactilia asociada a porfiria cutánea tarda (PCT). Según la bibliografía consultada, dicha asociación no ha sido previamente reportada
