bromochloroacetic-acid and Syndrome

In the last few years the progresses in molecular analysis allow better definitions of ichthyoses and lead to the necessity of a new classification and a review of nomenclature of inherited ichthyoses. So, in 2007 the First Consensus Conference on Ichthyoses was performed. We present here a short review of the new classification of syndromic ichthyoses together with clinical and molecular features.

Topics: Humans; Ichthyosis; Keratins; Syndrome

The authors present a case of clear cell sarcoma (CCS) in which the tumor originated in the S-1 nerve root and had been previously diagnosed as psammomatous melanotic schwannoma (PMS). This is the third case of a spinal nerve root origin for CCS reported in the English-language literature. The similar histogenesis of CCS and malignant melanoma supports the hypothesis that biological agents or immunotherapy are potentially important areas of investigation. The patient underwent S1-3 laminectomy and gross-total resection of the mass lesion. The border of the resection was extended 1 cm distal to the tumor margin. The postoperative period was uneventful. The new histopathological diagnosis was CCS (malignant melanoma of soft tissue). Despite total resection, the patient returned with disseminated disease at the 18-month follow-up visit. His follow-up magnetic resonance image of the lumbar spine revealed sacral L5-S3 involvement of the vertebral bodies along with disseminated cauda equina seeding. A CCS originating from peripheral nerves is quite rare. The histopathological and immunohistochemical appearance of CCSs resembles those of PMSs. Surgery should be the first choice of treatment.

Topics: Adolescent; Adult; Antigens, Neoplasm; Biomarkers, Tumor; Breast Neoplasms; Diagnosis, Differential; Diagnostic Errors; Female; Fibroadenoma; Humans; Keratins; Male; Melanins; Melanoma-Specific Antigens; Neoplasm Invasiveness; Neoplasm Proteins; Neoplasm Recurrence, Local; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Nerve Sheath Neoplasms; Neurilemmoma; Peripheral Nervous System Neoplasms; Pigmentation Disorders; Prognosis; S100 Proteins; Sacrococcygeal Region; Sarcoma, Clear Cell; Spinal Nerve Roots; Syndrome; Vimentin

Ichthyosis bullosa of Siemens (IBS, MIM 146800) is a unique congenital ichthyosis characterized by mild epidermal hyperkeratosis over flexural areas, blister formation and the development of superficially denuded areas of hyperkeratotic skin. It is clinically difficult to distinguish severe IBS from mild bullous congenital ichthyosiform erythroderma (BCIE, MIM 113800). In the current literature, 19 IBS families with keratin 2e (K2e) mutations have been reported, despite only five IBS families having been reported before the first identification of K2e mutation in 1994. We studied four patients from three Japanese IBS families. They had previously been misdiagnosed as having BCIE before the correct diagnosis was made after mutation detection. To detect the pathogenic mutations, we performed direct sequencing of the entire coding regions of KRT2E encoding K2e in the patients and healthy family members. K2e mutations, a 1469T-->C transition (L490P) and a 1477G-->A transition (E493K) within the conserved 2B helix termination motif of the rod domain were detected in the families and the definite diagnosis of IBS was made in the four cases. The present results indicate that IBS is not such a rare entity as was previously thought, and accurate diagnosis is now available by mutation analysis.

Topics: Adult; Child; Child, Preschool; Diagnosis, Differential; DNA Mutational Analysis; Female; Humans; Hyperkeratosis, Epidermolytic; Ichthyosis; Japan; Keratin-2; Keratins; Male; Middle Aged; Pedigree; Skin; Syndrome

Topics: Gene Expression; Genetic Therapy; Humans; Keratins; Mutation; Phenotype; Skin Diseases, Genetic; Syndrome

Meesmann's corneal dystrophy (OMIM 122,100) is a rare autosomal dominant disorder of the corneal epithelium. It manifests in early childhood and affects both eyes. The disease is characterized by variable patterned dot-like corneal opacities and intraepithelial vesicles, which can be seen by slit-lamp examination and retro-illumination. Further signs include punctate erosions, lacrimation, photophobia, and blepharospasm. Vision is usually only slightly diminished. By histology, the corneal epithelium is irregularly thickened. It shows vacuolated epithelial cells and intraepithelial formation of vesicles. By electron microscopy fibrogranular aggregates are seen in the cytoplasm of epithelial cells.. Linkage analyses in descendants of the family described by Meesmann and Wilke and other affected kinships showed that the putative genetic defect locates within the keratin type I gene cluster on chromosome 17 (17q12-21). Molecular genetic analyses in more than ten affected families showed that mutations in the cornea-specific keratin genes K3 and K12 represent the causative genetic defects of the disease phenotype.. Comparative studies in autosomal dominant skin disorders of cornification suggest that the mutations identified in patients with Meesmann's corneal dystrophy exert dominant negative effects on keratin filament assembly. Disturbed filament formation results in intracellular keratin clumping, identifiable as fibrogranular aggregates. As a result the mechanical resilience of the affected cells and the epithelial tissue appears markedly reduced. Whether abnormalities of functionally related structural proteins, e.g. desmosomal components, could result in a phenotype similar to Meesmann and Wilke's corneal dystrophy remains to be seen.

Topics: Child; Cornea; Corneal Dystrophies, Hereditary; DNA Mutational Analysis; Genetic Linkage; Genotype; Germany; Humans; Ireland; Japan; Keratins; Mutation; Mutation, Missense; North America; Phenotype; Syndrome

A 42-year-old man presented with painful toenails which were overcurved transversely and onycholytic. Examination revealed that all toenails, the thumbs and index fingers were similarly affected. In addition, he had a small area of leukokeratosis in the mouth, epidermal cysts of the scrotal skin and a small area of hyperkeratosis on the ulnar borders of his hands. His characteristic nail changes began in the great toenails at the age of 20 years. After renal transplantation at age 39, the other nails changed and he developed the features described above. His sister has overcurvature of the fifth toenails. A diagnosis of pachyonychia congenita tarda was made. His case is compared with 14 other reported cases of this rare syndrome.

Topics: Adult; Age of Onset; Epidermal Cyst; Genetic Predisposition to Disease; Humans; Keratins; Kidney Transplantation; Leukoplakia, Oral; Male; Nails, Malformed; Scrotum; Syndrome

Pachyonychia congenita (PC) comprises a heterogeneous group of autosomal dominantly inherited conditions showing characteristic nail thickening and associated signs such as palmoplantar keratoderma, follicular keratoses, and mucosal leukokeratoses. Less frequently epidermal cysts, hairshaft abnormalities, natal teeth and laryngeal involvement may be seen. Phenotypically and genetically two major forms of PC are recognized, pachyonychia congenita Jadassohn-Lewandowsky/PC type I (Medelian inheritance in man-MIM-167200) and pachyonychia congenita Jackson-Lawler/PC type II (MIM 167210). Both conditions show nail deformities, focal palmoplantar keratoderma, and follicular hyperkeratoses. Diagnostically relevant are leukokeratoses of the oral mucosa in patients with PC type I. In contrast individuals affected with PC type II show premature dentition and multiple pilosebaceous cysts predominantly affecting the upper trunk. The latter closely resemble eruptive vellus hair cysts and steatocystoma multiplex. By mutational analysis keratin K6a and K16 gene mutations have been detected in patients with PC type I, and keratin K6b and K17 gene mutations have been shown to be the underlying genetic defect in patients with PC type II.

Topics: Darier Disease; Ectodermal Dysplasia; Humans; Keratins; Keratoderma, Palmoplantar; Leukoplakia, Oral; Mutation; Nails, Malformed; Syndrome

Restrictive dermopathy (RD) is a lethal autosomal recessive genodermatosis (MIM No. 275210) in which tautness of the skin causes fetal akinesia or hypokinesia deformation sequence (FADS). Polyhydramnios with reduced fetal movements is followed by premature delivery at around 31 weeks gestation. Manifestations include a tightly adherent, thin, translucent skin with prominent vessels, typical facial changes, generalized joint contractures, enlarged fontanelles, dysplasia of clavicles, respiratory insufficiency, and an enlarged placenta with short umbilical cord. Histologic abnormalities of the skin include thin dermis with paucity and hypoplasia of the appendages and abnormally arranged collagen bundles. Elastic fibers are nearly missing. The subcutaneous fat is slightly increased. These skin findings usually appear after 22 or 24 weeks of gestation, which is why prenatal diagnosis with skin biopsy may fail. This disease is easily differentiated from other congenital FADS, such as Pena-Shokeir syndrome, COFS syndrome, Parana hard-skin syndrome, etc. We report on an affected boy of consanguineous parents and 30 previous cases are reviewed.

Topics: Calcification, Physiologic; Chromosome Inversion; Chromosomes, Human, Pair 9; Collagen; Contracture; Fatal Outcome; Female; Fetal Growth Retardation; Genes, Recessive; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Karyotyping; Keratins; Kyphosis; Male; Natal Teeth; Pregnancy; Skin Diseases; Syndrome

Olmsted syndrome is a rare disorder characterized by a mutilating palmoplantar keratoderma and periorificial keratotic plaques. It begins in early childhood and is complicated by the development of painful flexion contractures, constrictions, and autoamputations of the digits. Only 11 cases of Olmsted syndrome have been reported to date. However, no biochemical abnormalities in the skin were reported in any of these cases.. We report the 12th case of Olmsted syndrome. In addition, we describe a keratin abnormality found in a skin specimen obtained from our patient. The specimen showed a suprabasilar staining pattern with AE1, an antibody that shows only basilar staining in normal skin.. We report the 12th case of Olmsted syndrome, review the literature, and describe a keratin abnormality that was found in our patient's skin specimen.

Topics: Child; Female; Humans; Keratins; Keratoderma, Palmoplantar; Syndrome

Abnormalities of skin pigmentation are known to be associated sometimes with cardiovascular diseases. Such cases have been reported first in 1954 (14), then in 1962 (16) and 1966 (11), leading to the individualization of the leopard syndrome. In 1973 Rees et al. (21) described a lentiginosis, cardiac myxoma association, and this in turn resulted, in 1985, in a new syndrome (4) supported by several similar findings. We report here a new case with this association.

Topics: Adult; Cardiomyopathies; Epidermis; Heart Atria; Humans; Keratins; Lentigo; Male; Melanocytes; Myxoma; Syndrome

The association of congenital anomalies and pancytopenia is encountered in several clinical syndromes. Among these, Fanconi anemia is by far the most prevalent, and consequently best known. As a result, other similar conditions, such as dyskeratosis congenita and particularly WT syndrome, are often mistaken for Fanconi anemia. However, at a closer look, the type of congenital anomalies, the mode of inheritance, cytogenic and other laboratory findings allow clear differentiation between these 3 syndromes.

Topics: Abnormalities, Multiple; Anemia, Aplastic; Diagnosis, Differential; Fanconi Anemia; Female; Humans; Keratins; Male; Pancytopenia; Skin Diseases; Syndrome

Topics: Alopecia Areata; Child; Collagen Diseases; DNA; Genetic Counseling; Humans; Keratins; Male; Nevus; Pharmaceutical Preparations; Pharmacogenetics; Research; Skin Abnormalities; Skin Diseases; Skin Diseases, Vesiculobullous; Skin Neoplasms; Syndrome

Disturbances in the process of normal cornification leading to pathologic scaling provide the pathophysiologic basis for the ichthyoses. These disturbances may result from either abnormalities in protein metabolism (keratinization) (i.e., the "bricks") or in lipid metabolism (i.e., the "mortar") (Fig. 1). The evidence linking the various ichthyoses to defects in protein or lipid metabolism have been reviewed. It is likely that future advances will lead not only to a more complete understanding of the pathogenesis of these disorders, but also will shed significant light on the normal stratum corneum functions of barrier formation and desquamation, as well as lead the way to more rational and effective therapies. In recent years, prenatal diagnosis has been successfully performed in several of the ichthyoses. It is likely that improvements in our ability to prenatally diagnose those disorders will advance hand-in-hand with further progress in unraveling their underlying causes.

Topics: Animals; Cholesterol Esters; Epidermis; Fatty Acids, Essential; Female; Fetal Diseases; Humans; Ichthyosis; Keratins; Lipidoses; Mice; Pregnancy; Prenatal Diagnosis; Refsum Disease; Steryl-Sulfatase; Sulfatases; Syndrome; X Chromosome

Lichen planus (LP) and discoid lupus erythematosus (DLE) are separate disease entities. Nevertheless, patients with a so-called "overlap syndrome" have been described occasionally. The aim of the present study was to establish whether the LE/LP overlap syndrome, based on clinical and routine histological features, could be delineated from DLE or LP using immunohistochemical techniques. Formalin-fixated, paraffin-embedded skin biopsies of patients with DLE, LP and the overlap syndrome were compared regarding immunohistochemical markers for epidermal growth and differentiation and extracellular matrix components. With the markers for extracellular matrix proteins, it was possible to delineate the overlap syndrome from LP. This was not possible for the overlap syndrome and DLE. These findings might indicate that the LE/LP overlap syndrome could be considered as LP-like DLE rather than as a distinct disease entity.

Topics: Adult; Aged; Biomarkers; Biopsy, Needle; Culture Techniques; Diagnosis, Differential; Epidermal Growth Factor; Extracellular Matrix Proteins; Female; Humans; Immunohistochemistry; Keratins; Lichen Planus; Lupus Erythematosus, Discoid; Male; Middle Aged; Syndrome

A 30-year-old man presented with lesions on his oral mucosa and soles. There were no similar complaints in his family members. The dermatological examination revealed follicular hyperkeratosis on his trunk and upper extremities and flesh-colored, firm cystic lesions on his axillae. He had focal, painful, hyperkeratotic areas sited particularly on both his soles and palms. In addition to these, leukokeratosis and ulcerative areas on buccal, labial mucosa, tongue, and at corners of the mouth, and complete loss of teeth was observed. The proximal layering was revealed on all of his nails. The laboratory investigations produced normal results except the deficiency of immunoglobulin A. The psychiatric examination revealed mild mental retardation. Keratin gene (KRT6a, KRT6b, KRT16, and KRT17) mutations for pachyonychia congenita were negative. He got removable dental prosthesis because of inadequate alimentation. Squamous cell cancer developed on lower lip mucosa during follow-up. We present an individual who had different nail dystrophy, epidermal cysts, mental retardation, blepharitis, complete loss of teeth, and negative keratin gene mutations for pachyonychia congenita and developed squamous cell cancer on the oral leukokeratosis lesions. We think that the present case may be an unusual new type of pachyonychia congenita.

Topics: Adult; Carcinoma, Squamous Cell; Epidermal Cyst; Humans; Intellectual Disability; Keratins; Keratosis; Leukoplakia, Oral; Lip Neoplasms; Male; Mouth, Edentulous; Oral Ulcer; Pachyonychia Congenita; Syndrome

To evaluate the endothelial cell layer in patients with Fuchs' uveitis syndrome (FUS) with respect to the type and distribution of keratic precipitates (KP), endothelial cell morphology, and endothelial cell density (ECD), using in vivoconfocal microscopy (IVCM).. Forty eyes of 40 patients (mean age of 32.2 ± 12.5 years) with the clinical diagnosis of FUS were evaluated with IVCM (Confoscan 3.0, Vigonza, Italy). KP were classified as type I (small, round), type II (stippled), type III (dendritiform), and type IV (globular). When >1 KP type was present, differentiation between the predominant and less frequent KP was made as 'primary' and 'secondary'. ECD was measured and compared with age-matched 60 control subjects. Endothelial blebs were classified as small (3-10 μm) or large (>10 μm).. In 36 (90.0%) cases with FUS, more than one KP type was observed with IVCM. Type III (dendritiform) KP was the most frequently observed primary KP type (85.0%), followed by type II (stippled) KP (15.0%). Secondary KP included type II (58.3%), type IV (globular) (27.8%), and type III (13.9%). The mean endothelial cell density of eyes with FUS (2588 ± 396 cells/mm(2)) was significantly lower than that of control subjects (2930 ± 364 cells/mm(2)) (t-test; P<0.001). Eyes with FUS had lower proportion of hexagonal cells and higher percentage of polymegethism compared with the uninvolved contralateral eyes. Endothelial blebs (21 small, 16 large blebs) were observed in 37 (92.5%) eyes.. FUS is characterized by dendritiform KP and is associated with decreased ECD and altered endothelial cell morphology.

Topics: Adult; Case-Control Studies; Endothelium, Corneal; Epithelioid Cells; Female; Humans; Keratins; Male; Microscopy, Confocal; Syndrome; Uveitis, Anterior

To report Descemet's stripping endothelial keratoplasty (DSEK) as a treatment for corneal edema associated with toxic anterior segment syndrome.. A 75-year-old woman presented with decreased vision in her left eye after uneventful phacoemulsification. She was diagnosed with toxic anterior segment syndrome and a DSEK was performed. Histologic sections were examined after staining with hematoxylin and eosin, periodic acid Schiff, and Masson trichrome; immunoperoxidase reactions were used to identify cytokeratins, vimentin, and alpha-smooth muscle actin.. The corneal endothelium was selectively replaced by the DSEK technique. Descemet's membrane and endothelium were stripped from the recipient's stroma, and an 8-mm-diameter donor button consisting of posterior stroma and healthy endothelium was folded and implanted through a 5-mm incision. An air bubble was used to press the donor tissue against the recipient cornea, allowing it to attach without sutures. Corneal edema and visual acuity improved. Histopathologic evaluation of the DSEK specimen disclosed a multilaminar retro-Descemet's fibrous membrane in which many of the constituent fibroblasts contained scattered pigment granules and stained for both vimentin and cytokeratin with immunoperoxidase methods.. To the best of our knowledge, this is the first reported case of successful DSEK in a patient with corneal decompensation resulting from toxic anterior segment syndrome exhibiting a retrocorneal fibrous membrane. Visual recovery was rapid, and refractive changes were minimal compared with traditional penetrating keratoplasty. The immunoperoxidase staining strongly suggests that the retrocorneal fibrous membrane was created by dysplastic corneal endothelial cells.

Topics: Aged; Anterior Eye Segment; Corneal Edema; Descemet Stripping Endothelial Keratoplasty; Female; Humans; Immunoenzyme Techniques; Keratins; Phacoemulsification; Postoperative Complications; Syndrome; Treatment Outcome; Vimentin; Visual Acuity

The objective of this study was to analyze the expression of matrix metalloproteinases (MMPs) 1, 7, and 26 in odontogenic keratocysts (OKCs) associated with Gorlin syndrome (SOKCs) and nonsyndrome OKCs (NSOKCs).. Twenty-one SOKCs and 20 NSOKCs were evaluated for epithelial expression of MMP-1, MMP-7, and MMP-26 and for mesenchymal expression of MMP-1 by immunohistochemistry.. Strong epithelial positivity to MMP-1 was observed in 76% of SOKCs and in 15% of NSOKCs (P < .05). Strong mesenchymal immunoreactivity to MMP-1 was observed in 38% of SOKCs and in 20% of NSOKCs (P > .05). Epithelial immunoreactivity to MMP-7 was strongly positive in 67% of SOKCs and in 40% of NSOKCs (P > .05). For MMP-26, strong positivity was found in 62% of SOKCs, in contrast to 35% of NSOKCs (P > .05).. MMPs-1, -7 and -26 may play important roles in the biology of OKCs. Furthermore, the presence of these proteases at higher levels in SOKCs may help to explain increased OKC aggressiveness associated with nevoid basal cell carcinoma syndrome.

Topics: Basal Cell Nevus Syndrome; Female; Humans; Immunohistochemistry; Keratins; Male; Matrix Metalloproteinase 1; Matrix Metalloproteinase 7; Matrix Metalloproteinases, Secreted; Odontogenic Cysts; Syndrome

Naegeli-Franceschetti-Jadassohn syndrome (NFJS) is a rare autosomal dominant disorder characterized by loss of dermatoglyphics, reticulate hyperpigmentation of the skin, palmoplantar keratoderma, abnormal sweating, and other developmental anomalies of the teeth, hair, and skin. We recently demonstrated that NFJS is caused by heterozygous nonsense or frameshift mutations in the E1/V1-encoding region of KRT14, but the mechanisms for their deleterious effects in NFJS remain elusive. In this study, we further expand the spectrum of NFJS-causing mutations and demonstrate that these mutations result in haploinsufficiency for keratin 14 (K14). As increased apoptotic activity was observed in the epidermal basal cell layer in NFJS patients and as previous data suggested that type I keratins may confer resistance to tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis in epithelial tissues, we assessed the effect of down-regulation of KRT14 expression on apoptotic activity in keratinocytes. Using a HaCaT cell-based assay, we found that decreased KRT14 expression is associated with increased susceptibility to TNF-alpha-induced apoptosis. This phenomenon was not observed when cells were cultured in the presence of doxycycline, a known negative regulator of TNF-alpha-dependant pro-apoptotic signaling. Collectively, our results indicate that NFJS results from haploinsufficiency for K14 and suggest that increased susceptibility of keratinocytes to pro-apoptotic signals may be involved in the pathogenesis of this ectodermal dysplasia syndrome.

Topics: Apoptosis; Cell Line; Child; Female; Gene Expression Regulation; Genetic Predisposition to Disease; Humans; Keratin-14; Keratinocytes; Keratins; Mutation; Skin Abnormalities; Skin Diseases; Syndrome; Tumor Necrosis Factor-alpha

Global developmental delay is a serious social problem. It is often unrecognized and the phenotypes are inadequately studied. To investigate the phenotypes of children with aspecific central nervous system (CNS) impairment (poor speech, maladaptive behavioral symptoms such as temper tantrums, aggressiveness, poor concentration and attention, impulsiveness, and mental retardation).. Tertiary care hospital.. Three children (two male siblings, and one unrelated girl).. We used the results from clinical neurological evaluations; imaging and electrodiagnostic studies; metabolic and genetic tests; skin biopsies and bone mineral densitometry. All three children suffered from (A) global developmental delay, (B) osteopenia, and (C) identical skin defects. The skin ultrastructural abnormalities were abnormal keratin differentiation, consisting of hyperkeratosis and granular layer thickening; sweat gland abnormalities, consisting of focal, cytoplasmic clear changes in eccrine secretory cells; and melanocyte abnormalities, with both morphological changes (reduced number and size without evident dendritic processes), and functional changes (defects in the migration of melanosomes in the keratinocytes). These patients present a previously unrecognized syndrome. We retain useful to report this new association, to be recognized, in the next future, as a specific key-sign of a well-defined genetic defect.

Topics: Biopsy; Bone Diseases, Metabolic; Child; Child, Preschool; Developmental Disabilities; Ectoderm; Female; Humans; Intellectual Disability; Keratins; Male; Melanocytes; Siblings; Skin; Sweat Glands; Syndrome

Topics: CD56 Antigen; Encephalocele; Fetus; Gene Expression Regulation, Developmental; Humans; Keratin-20; Keratin-7; Keratins; Liver; Polycystic Kidney Diseases; Polydactyly; Syndrome

Naegeli-Franceschetti-Jadassohn syndrome (NFJS) and dermatopathia pigmentosa reticularis (DPR) are two closely related autosomal dominant ectodermal dysplasia syndromes that clinically share complete absence of dermatoglyphics (fingerprint lines), a reticulate pattern of skin hyperpigmentation, thickening of the palms and soles (palmoplantar keratoderma), abnormal sweating, and other subtle developmental anomalies of the teeth, hair, and skin. To decipher the molecular basis of these disorders, we studied one family with DPR and four families with NFJS. We initially reassessed linkage of NFJS/DPR to a previously established locus on 17q11.2-q21. Combined multipoint analysis generated a maximal LOD score of 8.3 at marker D17S800 at a recombination fraction of 0. The disease interval was found to harbor 230 genes, including a large cluster of keratin genes. Heterozygous nonsense or frameshift mutations in KRT14 were found to segregate with the disease trait in all five families. In contrast with KRT14 mutations affecting the central alpha -helical rod domain of keratin 14, which are known to cause epidermolysis bullosa simplex, NFJS/DPR-associated mutations were found in a region of the gene encoding the nonhelical head (E1/V1) domain and are predicted to result in very early termination of translation. These data suggest that KRT14 plays an important role during ontogenesis of dermatoglyphics and sweat glands. Among other functions, the N-terminal part of keratin molecules has been shown to confer protection against proapoptotic signals. Ultrastructural examination of patient skin biopsy specimens provided evidence for increased apoptotic activity in the basal cell layer where KRT14 is expressed, suggesting that apoptosis is an important mechanism in the pathogenesis of NFJS/DPR.

Topics: Apoptosis; Biopsy; Codon, Nonsense; Dermatoglyphics; Ectodermal Dysplasia; Female; Frameshift Mutation; Genes, Dominant; Humans; Keratin-14; Keratins; Lod Score; Male; Microsatellite Repeats; Mutation; Pedigree; Polymerase Chain Reaction; Protein Structure, Tertiary; Sweat Glands; Syndrome

Topics: Adult; Humans; Ichthyosis; Keratins; Male; Syndrome

Topics: Adult; Amino Acid Sequence; Ectodermal Dysplasia; Female; Humans; Keratins; Keratoderma, Palmoplantar; Keratosis; Mouth Diseases; Mutation, Missense; Nails, Malformed; Proline; Syndrome

Topics: Abnormalities, Multiple; Adult; Child; Corneal Diseases; Ear, External; Epithelium, Corneal; Eye Abnormalities; Female; Fingers; Humans; Keratin-3; Keratins; Lacrimal Apparatus; Limbus Corneae; Stem Cells; Syndactyly; Syndrome; Tooth Abnormalities

The ductal plate abnormality of the liver in fetuses with the Meckel-Gruber syndrome has been well characterised, but its aetiology remains unknown. We have analysed liver structure in six fetuses with this syndrome, using routine histology, immunocytochemistry, and electron microscopy.. Liver tissue from six fetuses of 11-27 weeks gestational age was examined by immunoperoxidase staining with antigens to cyokeratin (AE1/3) and polyclonal CEA. We also examined the ultrastructure of the syndromic fetal liver. The findings were compared with livers of control fetuses obtained from miscarriages, of similar size and gestational age but without dysmorphic features or developmental anomalies.. The ductal plate abnormality was present in all the fetuses with the Meckel-Gruber syndrome. There were abnormalities of biliary excretion in all syndromic fetuses. Ultrastructural studies of the portal tract revealed abnormal collagen bundles in the Meckel-Gruber syndrome.. Our findings, in conjunction with other reports in the literature, suggest that the ductal plate abnormality may be caused by failure of anastomosis of the intra- and extrahepatic biliary systems, perhaps in association with abnormalities of the portal tract stroma and biliary excretion.

Topics: Abnormalities, Multiple; Bile Ducts, Intrahepatic; Biomarkers; Carcinoembryonic Antigen; Fetal Development; Fetus; Gestational Age; Humans; Immunoenzyme Techniques; Keratins; Liver; Syndrome

Transgrediens et progrediens palmoplantar keratoderma, known as Greither's syndrome, was originally described in 1952 and is characterized by diffuse keratoderma of the palms and soles, extending to the back aspects (transgrediens) and involving the skin over the Achilles' tendon. Patchy hyperkeratosis also develops on the shins, knees, elbows, and sometimes on the skin flexures. We describe two unrelated families affected with Greither's syndrome, in which the same dominant missense mutation gave rise to the amino acid change N188S in K1. The previously reported cases of Greither's syndrome showed phenotypic variability suggestive of different underlying gene defects. Our findings suggest that at least some cases of Greither's syndrome are caused by keratin mutations.

Topics: Adolescent; Female; Humans; Infant; Keratin-1; Keratins; Keratoderma, Palmoplantar; Male; Mutation, Missense; Pedigree; Syndrome

Metastatic cancer of unknown primary site (CUP syndrome) comprises 2-5% of all solid malignant tumors. One should distinguish between initial CUP (primary tumor later detected) and the true CUP syndrome (primary tumor remains unknown for a patient's lifetime despite thorough diagnostic work-up). For initial CUP, the most important auxiliary diagnostic method is immunohistochemistry, which should be applied in a two-step algorithmic fashion. Firstly, a small marker panel (including certain cytokeratins) yields a preliminary categorization of the tumor. Secondly, selective, organ-specific markers (including recently established markers such as TTF-1 and uroplakin) and further tumor group markers may further subclassify or even identify the primary tumor. Although they are a heterogeneous group, true CUP tumors share some unique biological features such as an early metastatic phenotype and unusual metastasis patterns, and they mostly have a very poor prognosis. Even autopsy reveals the primary site in only 55-80% of cases, most commonly in the lung and pancreas. True CUP tumors, predominantly adenocarcinomas and poorly differentiated carcinomas, may exhibit unusual immunohistochemical phenotypes. Nevertheless, careful histologic and immunohistochemical examination are essential not only for determining the actual tumor immunophenotype but in particular for identifying therapy-responsive subgroups such as neck lymph node CUP, axillary lymph node CUP of females, neuroendocrine CUP, and germ cell tumor CUP of males. For CUP syndrome, future interdisciplinary research efforts are needed, such as gene expression profiling using microarrays. It is thus to be hoped that pathology will contribute to the elucidation of the largely still enigmatic pathogenesis of the CUP syndrome, to improve its diagnosis and classification and, finally, to aid in the development of more specific therapeutic regimens.

Topics: Biomarkers, Tumor; Female; Humans; Immunohistochemistry; Keratins; Neoplasms, Unknown Primary; Syndrome

To report the clinical features of the loose anagen hair syndrome and to test the hypothesis that the typical gap between the hair and the inner root sheath may result from hereditary defects in the inner root sheath or the apposed companion layer.. Case series.. A pediatric dermatology unit (referral center).. A consecutive sample of 17 children (13 girls). For 9 of them and their first-degree relatives, molecular analyses were performed in the K6HF gene with 50 appropriate controls.. Minoxidil therapy (5% lotion) in 11 patients for 1 to 12 months.. Clinical and follow-up features and determination of mutations in the K6HF gene.. Most patients had easily pluckable hair with no sign of scalp inflammation or scarring. Ten patients seldom cut their hair, and 4 had unmanageable hair. One patient had hypodontia. Two patients had an additional clinical phenotype of diffuse partial woolly hair. The family history was positive for loose anagen hair syndrome in 5 patients. Marked improvement was noted after treatment with 5% minoxidil lotion in 7 of the 11 patients treated. Polymerase chain reaction analysis of the gene segments encoding the alpha-helical 1A and 2B subdomains of K6hf, the type II cytokeratin exclusively expressed in the companion layer, was performed in 9 families. In 3 of these 9 families, a heterozygous glutamic acid and lysine mutation, E337K, was identified in the L2 linker region of K6HF.. Diffuse partial woolly hair can be associated with loose anagen hair syndrome. A keratin mutation, E337K in K6HF, was possibly causative in 3 of the 9 families studied. Another keratin, and possibly the type I partner of K6hf, could be responsible for loose anagen hair syndrome in other patients, or the gene involved may be a minor gene.

Topics: Child; Child, Preschool; Female; Hair Diseases; Humans; Keratins; Male; Syndrome

The purpose of this study was to identify the in vivo microstructural characteristics of an animal model of 'epithelialization of the endothelium' that are similar in appearance to the in vivo confocal microscopical appearance of corneal endothelium previously thought to be diagnostic of irido-corneal endothelial syndrome, and correlate these observations with ex vivo in situ confocal microscopical analysis. A rat model (n = 8 eyes)of transient 'epithelialization of the endothelium' resulting from superficial corneal trauma, was developed and analysed using in vivo confocal microscopy. One animal was killed at 48 hand the cornea was immuno-labelled and analysed, using ex vivo in situ confocal digital image reconstruction. Reversible 'epithelialization of the endothelium' was observed by in vivo confocal microscopy 48 h after superficial corneal trauma in all eight eyes. Ex vivo in situ analysis failed to demonstrate immunohistological characteristics of epithelialization. In vivo confocal microscopy is based on optical principles, and as a result various structural alterations may present with apparently identical characteristics that should be interpreted cautiously, on the basis of the presented clinicopathological observations.

Topics: Animals; Antibodies, Monoclonal; Cell Movement; Corneal Diseases; Endothelium, Corneal; Epithelium, Corneal; Female; Iris Diseases; Keratins; Microscopy, Confocal; Models, Animal; Rats; Rats, Wistar; Syndrome

Hay-Wells syndrome, also known as ankyloblepharon-ectodermal dysplasia-clefting (AEC) syndrome (OMIM 106260), is a rare autosomal dominant disorder characterized by congenital ectodermal dysplasia, including alopecia, scalp infections, dystrophic nails, hypodontia, ankyloblepharon and cleft lip and/or cleft palate. This constellation of clinical signs is unique, but some overlap can be recognized with other ectodermal dysplasia syndromes, for example ectrodactyly--ectodermal dysplasia--cleft lip/palate (EEC; OMIM 604292), limb--mammary syndrome (LMS; OMIM 603543), acro-dermato-ungual-lacrimal-tooth syndrome (ADULT; OMIM 103285) and recessive cleft lip/palate--ectodermal dysplasia (CLPED1; OMIM 225060). We have recently demonstrated that heterozygous mutations in the p63 gene are the major cause of EEC syndrome. Linkage studies suggest that the related LMS and ADULT syndromes are also caused by mutations in the p63 gene. Thus, it appears that p63 gene mutations have highly pleiotropic effects. We have analysed p63 in AEC syndrome patients and identified missense mutations in eight families. All mutations give rise to amino acid substitutions in the sterile alpha motif (SAM) domain, and are predicted to affect protein--protein interactions. In contrast, the vast majority of the mutations found in EEC syndrome are amino acid substitutions in the DNA-binding domain. Thus, a clear genotype--phenotype correlation can be recognized for EEC and AEC syndromes.

Topics: Abnormalities, Multiple; Amino Acid Sequence; Ankylosis; Base Sequence; Binding Sites; Blepharitis; Child; Cleft Lip; Cleft Palate; DNA; DNA Mutational Analysis; DNA-Binding Proteins; Female; Filaggrin Proteins; Genes, Tumor Suppressor; Heterozygote; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Male; Membrane Proteins; Molecular Sequence Data; Mutation, Missense; Phosphoproteins; Protein Structure, Tertiary; Sequence Alignment; Sequence Homology, Amino Acid; Skin; Syndrome; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins

Olmsted syndrome is an uncommon inherited disorder of keratinization that presents mutilating palmoplantar keratoderma, perioral hyperkeratosis, leukokeratosis and alopecia. We report a case of this rare syndrome diagnosed in a 48-year-old woman and confirms the existence of a generalized abnormality in keratin expression. Immunoreactivity in our case suggests an abnormal expression of keratins 5 and 14 similar to the observed in other hyperproliferative disorders.

Topics: Abnormalities, Multiple; Alopecia; Antibodies, Monoclonal; Female; Humans; Immunoenzyme Techniques; Keratins; Keratoderma, Palmoplantar; Leukoplakia, Oral; Middle Aged; Skin; Syndrome

Topics: Adenocarcinoma; Aged; Aqueous Humor; Biomarkers, Tumor; Carcinoembryonic Antigen; Cytological Techniques; Eye Neoplasms; Humans; Immunoenzyme Techniques; Immunophenotyping; Keratins; Lung Neoplasms; Male; Syndrome; Tomography, X-Ray Computed; Uveitis; Vitreous Body

Pseudomyxoma peritonei syndrome is a rare disease that originates from an adenomatous lesion of the appendix that, from pressure, perforates to gain access to the free peritoneal cavity. The relative sparing of the small bowel surfaces allows for complete cytoreduction even though many kilograms of mucinous tumour exist at other sites within the abdomen and pelvis. The purpose of this study was to examine the mechanism whereby the small bowel remains free of gross tumour and peritoneal surface polyps form.. Peritoneal surface polyps were harvested and examined grossly and histologically. A hypothesis for their formation on small bowel and small bowel mesentery was proposed. Polyps are known to be associated with repeated motion of enteric contents moving past adenomatous tissue so that, over time, an elongated stalk is created. We have repeatedly observed pedunculated polyps on the peritoneal surface of the small bowel in patients with pseudomyxoma peritonei syndrome. No other site within the peritoneal cavity has had a pseudomyxoma polyp located upon its surface.. The peristaltic motion of the small bowel causes adherent adenomatous tissue to develop a stalk on the peritoneal surface. Motion not only creates polypoid lesions but also repeatedly clears mucinous tumour cells from the small bowel surface. With pseudomyxoma peritonei and with other types of cancerous dissemination, prevention of adherence by motion may interfere with the implantation of malignant cells.

Topics: Biomarkers; Humans; Immunohistochemistry; Keratins; Peritoneal Neoplasms; Peritoneum; Polyps; Pseudomyxoma Peritonei; Syndrome

Topics: Adult; Diagnosis, Differential; Ectodermal Dysplasia; Female; Humans; Keratins; Mutation; Nail Diseases; Nails, Malformed; Phenotype; Polymerase Chain Reaction; Skin; Syndrome

To study the relationship between abnormal Sertoli cell differentiation and spermatogenic impairment, we examined the expression of Sertoli cell markers normally lost at puberty, cytokeratin 18 (CK18), anti-Müllerian hormone (AMH) and M2A antigen, in three children (aged 1-2 years), 50 adults (aged 19-45 years) with obstructive or non-obstructive azoospermia or oligozoospermia, and six patients (aged 1-18 years) with 5 alpha-reductase deficiency. There was CK18 and/or AMH expression, but never M2A antigen expression, associated with spermatogonial arrest or Sertoli cell-only (SCO) syndrome in infertile men. Loss of M2A antigen suggests the transition of Sertoli cells to an adult phenotype, while CK18 and/or AMH expression may be a manifestation of de-differentiation of Sertoli cells. In 5 alpha-reductase deficiency, there was a sequential loss of CK18, M2A antigen and AMH around puberty, associated with partial spermatogenesis. The persistence of immature Sertoli cells expressing M2A antigen was associated with prepubertal seminiferous cords and SCO syndrome. Therefore, 5 alpha-reductase deficiency may prevent the maturation of Sertoli cells, resulting in impairment of spermatogenesis, and loss of M2A antigen expression coincides with a critical step in the Sertoli cell maturation. High follicle stimulating hormone concentrations due to failure of normal Sertoli cell differentiation indicate a normal development pattern of the hypothalamic-pituitary-gonadal axis.

Topics: Adolescent; Adult; Anti-Mullerian Hormone; Antigens, Neoplasm; Cell Differentiation; Child; Child, Preschool; Cholestenone 5 alpha-Reductase; Choristoma; Glycoproteins; Growth Inhibitors; Humans; Infant; Infertility, Male; Keratins; Male; Middle Aged; Oligospermia; Oxidoreductases; Phenotype; Sertoli Cells; Syndrome; Testicular Hormones; Testis

Topics: Humans; Keratins; Keratoderma, Palmoplantar; Syndrome

The Papillon-Lefèvre and Haim Munk syndromes are characterized by the presence of both palmoplantar hyperkeratosis (PPK) and severe early onset periodontitis. It is the early onset periodontal disease component that distinguishes these from other more common forms of PPK. It has been proposed that the periodontal disease component may be a casual association in individuals with PPK. Genetic syndromes with palmoplantar keratosis and severe ealry onset periodontitis may be due to specific bacterial infections in individuals with PPK. Recently, keratin gene mutations have been identified in several conditions typified by palmoplantar keratosis. The present study sought to test the hypothesis that a keratin gene defect similar to those previously identified in other PPK conditions is responsible for the Haim Munk and the Papillon. Lefèvre syndromes. We have performed genetic linkage studies to test for linkage between polymorphic DNA loci within 2 cytokeratin gene families and the disease phenotype in Haim Munk syndrome and Papillon-Lefèvre syndrome. Families with individuals segregating for the Haim Munk syndrome and the Papillon-Lefèvre syndrome were examined to determine disease status, and genotyped for microsatellite DNA markers closely linked to the acidic (type I) and the basic (type II) cytokeratin genes on chromosomes 12 and 17. Genotype data were evaluated for microsatellite allele homozygosity in affected individuals. Results of these preliminary genetic studies suggest that the gene defect in Haim Munk syndrome is not due to a gene defect in either the type I or the type II keratin gene clusters. These findings suggest that Haim Munk syndrome may be genetically distinct from other more common forms of PPK that have been linked to the cytokeratin gene families, and suggest that mutations in genes other than keratin genes are responsible. Additional family studies are needed to confirm these preliminary findings.

Topics: Adult; Aggressive Periodontitis; Bacteria, Anaerobic; Child; Chromosome Mapping; Chromosomes, Human, Pair 12; Chromosomes, Human, Pair 17; Colony Count, Microbial; Female; Genetic Heterogeneity; Genetic Linkage; Genotype; Haplotypes; Humans; Keratins; Keratoderma, Palmoplantar; Male; Microsatellite Repeats; Multigene Family; Papillon-Lefevre Disease; Pedigree; Syndrome

Several clinical syndromes are characterized by ectodermal dysplasia (ED) in association with clefting of the lip and/or palate. In these syndromes, alopecia is primarily due to abnormalities of the hair shaft associated with increased hair fragility. Scalp dermatitis is yet another peculiar finding, primarily seen in the ankyloblepharon-ED-clefting (AEC) syndrome. We report on a 16-year-old patient with ectrodactyly-ED-clefting (EEC) syndrome, who exhibited a scarring alopecia due to deep folliculitis. On scanning electron microscopy, irregular torsion and longitudinal grooving of the hair shaft (pili torti et canaliculi) were observed. Quantitative determinations of the elastic and viscous parameters of hair demonstrated a normal viscosity but a significantly reduced hair elasticity, indicating either an abnormal composition or a disordered arrangement of microfibrils within the apparently normal keratin matrix. In contrast to the erosive scalp dermatitis of early onset in the AEC syndrome, alopecia in this case of EEC syndrome demonstrated follicular scarring with onset during puberty. We question a possible role of the anatomical hair abnormality in the pathogenesis of chronic deep folliculitis in this and clinically related syndromes.

Topics: Adolescent; Alopecia; Biophysical Phenomena; Biophysics; Cicatrix; Cleft Lip; Cleft Palate; Dermatomycoses; Ectodermal Dysplasia; Elasticity; Fingers; Folliculitis; Hair; Humans; Keratins; Malassezia; Male; Microscopy, Electron, Scanning; Puberty; Scalp Dermatoses; Staphylococcal Skin Infections; Syndrome; Viscosity

To test the hypothesis that the aberrant, cytokeratin-expressing cells that replace endothelium in the iridocorneal endothelial (ICE) syndrome are of endothelial origin.. Corneas from four patients with Chandler's syndrome and three with essential iris atrophy were examined by two-color immunofluorescence for simultaneous expression of cytokeratins and two markers of endothelial lineage: vimentin and the antigen recognized by the antiendothelial monoclonal antibody 2B4.14.1.. In six corneas, unequivocal endothelial staining for cytokeratins was present; in each of these, cells coexpressing cytokeratins and the two endothelial markers were clearly identifiable. In the remaining cornea, weak cytokeratin staining that colocalized with vimentin was present.. These results lend strong support to the hypothesis that the "epithelial-like" endothelial cells in ICE syndrome are cells of endothelial lineage rather than heterotopia of epithelial cells; these cells probably arise via a metaplastic transformation of preexisting endothelium.

Topics: Adult; Aged; Antibodies, Monoclonal; Corneal Diseases; Endothelium, Corneal; Fluorescent Antibody Technique, Indirect; Humans; Iris Diseases; Keratins; Metaplasia; Middle Aged; Syndrome; Vimentin

The pathogenesis of 'collodion baby' has not been clarified yet, and this descriptive term is thought to include several heterogeneous conditions. We report a collodion baby whose clinical features had changed to those of lamellar ichthyosis (LI) as the patient got older. By electron microscopy, skin specimens at 3 days of age revealed the presence of lipid inclusions within the cornified cells, abnormal lamellar granules in the granular layer keratinocytes and a lack of extracellular lamellar structure between the first cornified cell and the granular cell though the cornified cell envelope appeared to be normally formed. Immunohistochemical labeling showed normal distribution of keratins 1, 5, 10, 14, filaggrin/profilaggrin and cornified cell envelope proteins (involucrin, small proline-rich proteins and loricrin). These observations suggested that a collodion baby might have a normal cornified cell envelope and show morphologic changes similar to those of harlequin ichthyosis at birth, even though its underlying disorder is LI.

Topics: Abnormalities, Multiple; Ear; Filaggrin Proteins; Follow-Up Studies; Humans; Ichthyosis, Lamellar; Infant, Newborn; Intermediate Filament Proteins; Keratins; Male; Membrane Proteins; Microscopy, Electron; Skin; Syndrome

Kindler syndrome is a genodermatosis that combines clinical features of hereditary epidermolysis bullosa and poikiloderma congenitale. The ultrastructural level of blister formation has not been well characterized.. Two brothers with Kindler syndrome had a history of primarily acral blistering since infancy as well as photosensitivity. Blister formation was found through the basal layer. Marked tonofilament clumping was found in intact keratinocytes adjacent to the blisters. The younger brother (aged 21 years) had actinic keratoses, which have not been previously described in Kindler syndrome.. The findings of basal layer separation in both spontaneous and induced blisters in Kindler syndrome suggest this is the true level of blister formation. The finding of actinic keratoses in a young patient with Kindler syndrome suggests that some patients may be at increased risk for early solar-induced skin disease. The presence of clumped tonofilaments in keratinocytes adjacent to blistered areas suggests an abnormality of keratin 5 or 14 could be present and may play a role in blister formation in patients with Kindler syndrome.

Topics: Adult; Blister; Epidermolysis Bullosa; Humans; Intermediate Filaments; Keratinocytes; Keratins; Keratosis; Male; Photosensitivity Disorders; Rothmund-Thomson Syndrome; Skin; Syndrome

The triple A or Allgrove's syndrome (MIM*231550) is an autosomal recessive disease characterized by the triad of adrenocorticotropic hormone (ACTH) resistant adrenal insufficiency, achalasia and alacrima. Since its first description by Allgrove et al. (1978) more than 70 cases from all over the world have been reported. The syndrome manifests itself during the first decade of life with severe hypoglycaemic episodes which can cause sudden death. The frequent association with neurological disorders presenting as a mixed pattern of upper and lower motor neuropathy, sensory impairment, autonomic neuropathy and mental retardation may result in a severely disabling disease. As an additional feature some patients have hyperkeratosis of their palms and soles. We have performed a systematic genome linkage scan in eight triple A families of which three were consanguineous [including the large highly inbred kindred described by Moore et al. (1991)]. We obtained conclusive evidence for linkage of the triple A syndrome locus to markers on chromosome 12q13 (D12S368, theta max = 0, Zmax = 10.81) with no indication of genetic heterogeneity. Haplotype and multipoint analyses suggest that the gene is located on a chromosomal segment flanked by the markers D12S1629 and D12S312 which are 6 cM apart. This region harbors the type II keratin gene cluster, and potential candidate genes include SCN8A and HOXC genes.

Topics: Adrenal Insufficiency; Chromosome Mapping; Chromosomes, Human, Pair 12; Esophageal Achalasia; Female; Genetic Linkage; Humans; Keratins; Lacrimal Apparatus Diseases; Male; Multigene Family; Pedigree; Syndrome

Trichorhinophalangeal syndrome (TRPS) comprises a distinctive combination of hair, facial and bony abnormalities with variable expression. A 20-year-old man with TRPS was seen because of marked androgenetic alopecia. Scanning electron-microscopic studies of the hair revealed flattened hair with an elliptoid transverse section pattern. Mechanical behavior of the hair was abnormal with a significant increase in the viscous parameter, indicating a decreased intermolecular bridging within the keratin matrix. The dermatologist confronted with premature or marked alopecia in young adults should always consider the possibility of an underlying congenital syndrome involving the hair and prompt further investigation.

Topics: Adult; Alopecia; Elasticity; Finger Joint; Fingers; Hair; Humans; Keratins; Male; Microscopy, Electron, Scanning; Nose; Syndrome; Viscosity

A new patient with CHILD syndrome (congenital hemidysplasia, ichthyosiform erythroderma, and limb defects), the thirtieth in the literature, was observed for over three years. Initially, the right-sided lesion spared the breast area. At 10 months of age the trunk lesion extended to cover the entire area of the right chest. At age 20 months the patient developed linear, bandlike, keratotic, brown-black lesions on her left thigh that subsided within six weeks, leaving a slight hyperpigmentation. This patient was studied by routine histologic methods as well as with markers of keratinization and electron microscopy. In hematoxylin and eosinstained sections, parakeratosis and orthokeratosis alternated. In some parakeratotic areas, large granular cells, and in others, ghost granular cells, were present. The latter showed basophilic cytoplasm, and palestaining or vacuolated nucleus and were seen either above the normal granular layer or without it. Although regional variations existed, basal cell-type keratins as recognized by AE1 continued to be expressed in suprabasal layers. Filaggrin- and involucrin-positive layers were expanded, particularly the latter, down to the lower prickle cell layer. Ultrastructurally, numerous lamellar or membranous structures were found in upper layers of the epidermis, both intracellulary and intercellularly. Normal cementsomes coexisted with these abnormal lamellar structures, and it was thought that the latter represent modified cementsomes because the discharge of those from the cell periphery was often detected.

Topics: Arm; Epidermis; Female; Filaggrin Proteins; Follow-Up Studies; Humans; Hyperpigmentation; Ichthyosiform Erythroderma, Congenital; Infant; Infant, Newborn; Intermediate Filament Proteins; Keratinocytes; Keratins; Keratosis; Leg; Lichenoid Eruptions; Protein Precursors; Syndrome

Pachyonychia congenita (PC) is a rare autosomal dominant condition characterized by multiple ectodermal abnormalities. Patients with Jadassohn-Lewandowsky Syndrome (MIM #167200; PC-1) have nail defects (onchyogryposis), palmoplantar hyperkeratosis, follicular hyperkeratosis and oral leukokeratosis. Those with the rarer Jackson-Lawler Syndrome (MIM #167210; PC-2) lack oral involvement but have natal teeth and cutaneous cysts. Ultra-structural studies have identified abnormal keratin tonofilaments and linkage to the keratin gene cluster on chromosome 17 has been found in PC families. Keratins are the major structural proteins of the epidermis and associated appendages and the nail, hair follicle, palm, sole and tongue are the main sites of constitutive K6, K16 and K17 expression. Furthermore, mutations in K16 and K17 have recently been identified in some PC patients. Although we did not detect K16 or K17 mutations in PC families from Slovenia, we have found a heterozygous deletion in a K6 isoform (K6a) in the affected members of one family. This 3 bp deletion (AAC) in exon 1 of K6a removes a highly conserved asparagine residue (delta N170) from position 8 of the 1A helical domain (delta N8). This is the first K6a mutation to be described and this heterozygous K6a deletion is sufficient to explain the pathology observed in this PC-1 family.

Topics: Amino Acid Sequence; Base Sequence; DNA; Female; Genes, Dominant; Heterozygote; Humans; Keratins; Keratoderma, Palmoplantar; Leukoplakia; Male; Molecular Sequence Data; Nails, Malformed; Pedigree; Sequence Deletion; Syndrome

Brooke-Spiegler syndrome is characterized by the development of multiple trichoepitheliomas and cylindromas. In addition, multiple spiradenomas have been observed in this autosomal-dominant inherited disease. We report a 53-year-old woman with multiple cylindromas on the head and neck and multiple trichoepitheliomas on the face. Additionally, she had had since birth a plaque on the right side of her neck containing two nodules with features of both cylindroma and trichoepithelioma. Immunohistochemical investigations revealed in the basaloid cells of trichoepithelioma an expression of CK 5/6, CK 14, CK 17, CK 19 and vimentin. The cells of the cylindroma lacked vimentin but expressed additionally CK 7, CK 8 and CK 18. The occurrence of cylindroma and trichoepithelioma in a single nevoid plaque from a patient with Brooke-Spiegler syndrome implies an alteration in the stem cells of the folliculosebaceous-apocrine unit and could be characteristic of the disorder.

Topics: Antibodies, Monoclonal; Carcinoma, Adenoid Cystic; Eyebrows; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Neck; Neoplasms, Basal Cell; Neoplasms, Multiple Primary; Scalp; Skin Neoplasms; Syndrome

A corneal specimen obtained by surgery in a 55-year-old woman with Chandler's syndrome was studied by light and transmission electron microscopy as well as by immunocytochemistry. The pathologic features were abnormalities of the endothelially derived cells lining the posterior corneal surface with a fibrous material consisting of collagen fibrils, filaments and banded material similar to that found in the anterior part of Descemet's membrane observed between the endothelial cell layer and Descemet's membrane. The multilayered endothelial cell layer in our case was found to be strongly positive for cytokeratins K7 and KL1 and vimentin and negative for factor-VIII-related antigen, neuron-specific enolase, nerve tissue S-100 protein, epithelial membrane antigen, CD 68, actin and desmin. This immunohistochemical reaction pattern argues in favor of an epithelial origin for cells lining the endothelial cell layer in Chandler's syndrome.

Topics: Corneal Diseases; Endothelium, Corneal; Female; Humans; Immunoenzyme Techniques; Iris Diseases; Keratins; Keratoplasty, Penetrating; Middle Aged; Syndrome; Vimentin

Visual impairment resulting from retinal, subhyaloid, or vitreous hemorrhages in association with Tersons syndrome is often significant. The most common long-term sequelae that may result in permanent visual deficit is the formation of an epimacular membrane.. This report provides clinicopathologic documentation of epiretinal membrane proliferation secondary to Tersons syndrome. Pars plana vitrectomy was performed in 16 eyes of 11 patients with Tersons syndrome. After removal of vitreous hemorrhage, epimacular membranes were found in 10 eyes (62.5%). The posterior cortical vitreous and the epiretinal tissue were examined histologically.. Immunostainings with glial and retinal pigment epithelial cell markers showed that the majority of cells derived form the glia. Perls staining, specific for iron, showed that the high melanic-like component contained in the histopathologic samples corresponded to degradation of blood products secondary to chronic hemorrhage.. The high risk of epiretinal membrane formation and the toxicity of blood breakdown products over the inner retina worsen the long-term visual prognosis in Tersons syndrome. Early surgery is advocated in such cases.

Topics: Adolescent; Adult; Cell Membrane; Child, Preschool; Female; Fundus Oculi; Glial Fibrillary Acidic Protein; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Neuroglia; Retina; Retinal Diseases; S100 Proteins; Subarachnoid Hemorrhage; Syndrome; Vitrectomy; Vitreous Hemorrhage

Acanthosis nigricans (AN) comprises a broad spectrum of etiologic subtypes. The underlying pathomechanisms have not yet been completely clarified. We present a patient affected with a syndromelike AN subtype including disturbed epidermopoiesis as evidenced by immunohistologic findings and in situ hybridization.. A 54-year-old white man contracted AN during childhood. There were connate malformations consisting of webbed toes II/III on the right side and a supernumerary left mammilla. As an adult he developed psoriasis vulgaris, obesity, and latent diabetes mellitus, polycystic kidney and liver disease. With regard to keratin 6 mRNA, and the protein expression of keratin 6/16, KI-67, and proliferating cell nuclear antigen, the AN lesion showed moderate hyperproliferation. A much higher degree of hyperproliferation was evident in psoriatic areas of the patient's skin. In contrast to psoriatic tissue, basal keratinocytes of the AN showed an unusually high expression of keratin 18 and 19 protein.. The observation thus deals with a unique, syndromelike constellation of AN characterized by a particular epidermal pattern of moderate hyperproliferation. A further dysregulation of protein expression in the epidermis is indicated by the demonstration of the rare keratins 18 and 19 in basal keratinocytes of the AN lesion.

Topics: Abnormalities, Multiple; Acanthosis Nigricans; Humans; Keratins; Male; Middle Aged; Nipples; Polycystic Kidney Diseases; RNA, Messenger; Syndactyly; Syndrome

The immunocytologic characteristics of two formalin-fixed, paraffin-embedded corneas from patients with the iridocorneal endothelial (ICE) syndrome and unaffected control corneas were studied. Binding of polyclonal antisera to Factor VIII, S-100 protein, involucrin, neuron specific enolase (NSE), and the lectins peanut agglutinin and Ulex europaeus agglutinin-1 was performed using the standard peroxidase-anti-peroxidase method. We detected reactive patterns of monoclonal antibodies to cytokeratins (34BE12 is a 56-58 kD mouse IgG reactive to stratified epithelia; Pkk1 is a 44-54 kD mouse IgG reactive to simple epithelia; and KL1 is a 55-57 kD mouse IgG reactive to epidermis and simple epithelia) using the standard avidin-biotin complex method. Staining properties were similar for the polyclonal antisera, lectins, NSE, and chromogranin in corneas with ICE syndrome and in the controls. However, the cytokeratins 34BE12, Pkk1, and KL1 were detected in the endothelium of the corneas with the ICE syndrome but not in the controls. These findings suggest that various cytokeratins are expressed in the corneal endothelium in the ICE syndrome that are not expressed in unaffected corneal endothelium.

Topics: Antibodies, Monoclonal; Corneal Diseases; Endothelium, Corneal; Factor VIII; Humans; Immunoenzyme Techniques; Iris Diseases; Keratins; Microscopy, Electron, Scanning; Protein Precursors; S100 Proteins; Syndrome

Congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD) syndrome is a rare genetic disorder. The epidermal abnormalities associated with the unilateral ichthyosis have previously been examined only by morphology. In order to describe these abnormalities more completely we analyzed the expression of markers of epidermal differentiation (keratins and filaggrin), grew keratinocytes in culture, and correlated the results with ultrastructural features. Expression of all differentiation markers was significantly reduced or absent, whereas keratins K5 and K14 and keratins K6 and K16 were strongly expressed in lesional epidermis, suggesting that basal cell keratin expression was not down-regulated as in normal epidermis and that lesional keratinocytes mature via an abnormal pathway. When removed from the tissue and grown in culture, keratinocytes from lesional and non-lesional biopsies had similar phase microscopic morphology as well as keratin and profilaggrin expression, in contrast to the extreme differences in vivo. Lesional keratinocytes also had similar contents of keratin filaments and keratohyalin, but showed abnormal accumulation of intercellular vesicles and debris and altered cell-cell and cell-substratum interaction. Comparison of the results in tissue and in culture suggests that systemic or dermal factors influence the abnormal structural protein expression and ichthyosiform epidermal differentiation seen in CHILD syndrome, but that lesional keratinocytes maintain abnormalities in the secretion and accumulation of extracellular material in vitro similar to the lesional tissue in vivo.

Topics: Abnormalities, Multiple; Biopsy; Electrophoresis, Polyacrylamide Gel; Female; Filaggrin Proteins; Humans; Ichthyosis; Immunohistochemistry; Infant; Intermediate Filament Proteins; Keratins; Limb Deformities, Congenital; Skin; Skin Abnormalities; Syndrome

Pachyonychia congenita (PC) is a very rare hereditary disorder of keratinization. Immunohistological findings has so far been lacking. Reported in this paper is a case of Jadassohn-Lewandowsky type PC in a woman aged 18 years on which immunohistological investigations could be performed. Several monoclonal antibodies to filaggrin and keratin were used to stain tissue sections of lesional plantar skin, with a view to studying impairment of epidermal differentiation. While staining patterns comparable to those of normal skin were exhibited by anti-filaggrin and some antikeratins (RPN 1161, A51-B/H4), substantially altered immunostaining was recordable from other anti-keratins. Only superficial vital keratinocytes were stained by RKSE 60 against keratin 10 and K 8.12 against keratins 13 and 16. The authors, in other words, obtained information on expression of keratin 10, normally occurring in all suprabasal keratinocytes, as well as of the basal proliferation keratin 16 in the uppermost vital cell positions of PC lesion. The above results are likely to suggest impairment of keratin expression in cases of PC.

Topics: Adolescent; Epidermis; Female; Filaggrin Proteins; Frozen Sections; Humans; Hyperplasia; Immunohistochemistry; Intermediate Filament Proteins; Keratinocytes; Keratins; Keratoderma, Palmoplantar; Nails, Malformed; Syndrome; Tongue

We report on two cases of pachyonychia congenita, Jadassohn-Lewandowsky type, in a father and daughter. Histopathological examination revealed thickened, aggregated bundles of tonofilaments and an increased number of atypical keratohyalin granula, which is suggestive of an altered keratinization. Immunohistological staining with antibodies to cytokeratins (A45-B/B3, A51-B/H4, A53-B/A2, RPN 1161) was unchanged. Filaggrin could not be detected. Basal cells immunoreactive for calmodulin were markedly reduced or even absent in the rete ridges. Staining with a monoclonal antibody against Ki67 made epidermal cell hyperproliferation seem unlikely. The epidermal lectin binding was normal. C3 was detectable in vessel walls mainly of the stratum reticulare. The findings are discussed with reference to pachyonychia pathogenesis.

Topics: Adolescent; Adult; Autoantibodies; Female; Filaggrin Proteins; Humans; Hyperhidrosis; Immunohistochemistry; Keratins; Keratosis; Male; Nails, Malformed; Syndrome

A 29-year-old woman had unilateral essential iris atrophy, corneal endothelial changes, and absolute glaucoma. The enucleated eye was examined by routine light microscopy. Separate portions of unfixed fresh frozen cornea were sectioned and reacted with monoclonal antibodies against keratins, vimentin, and inflammatory cell markers. Stains for filamentous actin (f-actin) were performed using the 7-nitro-benz-2-oxa-1,3-diazolylphallacidin (NBD phallacidin) probe. In addition, portions of cornea and iris were examined by scanning and transmission electron microscopy. Immunocytochemical stains with anti-keratin antibodies showed reactivity only in the corneal epithelium of the patient and normal control. Immunoreactivity with anti-vimentin antibodies was observed in corneal endothelium and keratocytes of the patient and control, but was negative in the epithelium. Staining for f-actin appeared more pronounced in the corneal endothelium of the patient. Scanning electron microscopy of the corneal endothelium showed irregularity in cell size and shape and filopodial processes characteristic of migrating cells. Transmission electron microscopy disclosed abnormalities of Descemet's membrane and endothelium with a posterior collagenous layer. The corneal endothelium displayed normal junctional complexes without desmosomal junctions or increased microvillus projections. Increased 10-nm cytoplasmic filaments were noted consistent with the expression of vimentin. Occasional chronic inflammatory cells perturbed the corneal endothelium and were detected within the endothelial layer. Alterations in the endothelium and Descemet's membrane suggest the acquired nature of this disease.

Topics: Actins; Adult; Atrophy; Corneal Diseases; Endothelium, Corneal; Female; Glaucoma; Humans; Immunohistochemistry; Iris; Iris Diseases; Keratins; Microscopy, Electron; Microscopy, Electron, Scanning; Syndrome

A case of 'peeling skin syndrome' is reported. We have demonstrated a hitherto unreported keratohyalin abnormality and a four-fold increase of cellular retinoic acid binding protein, in one of two biopsies from an erythematous, scaling lesion.

Topics: Adult; Female; Humans; Ichthyosis; Keratins; Microscopy, Electron; Skin; Syndrome; Vitamin A

Two women with the iridocorneal endothelial syndrome had unilateral corneal edema, iris stromal atrophy, and glaucoma. Each underwent penetrating keratoplasty. Transmission electron microscopy of the corneal buttons disclosed a thin, normally structured Descemet's membrane bounded posteriorly by a posterior collagenous layer that contained banded and fibrillar tissue, indicating that the disorder was acquired after childhood. Scanning electron microscopy showed some degenerated corneal endothelial cells with filopodial cytoplasmic projections, suggesting endothelial migration. Transmission electron microscopy of the endothelium showed no signs of epithelial-like alteration, such as stratification, desmosomal junctions, or increased cytoplasmic fibrils. Immunohistochemical staining of fresh-frozen sections with monoclonal antibodies to keratin showed normal staining of the epithelium and no staining of the endothelium. Occasional lymphocytes were seen within the endothelium in one case but were also observed in one case of an inherited corneal disease, posterior polymorphous dystrophy, suggesting that they might be normal "passenger" cells migrating in the endothelial monolayer.

Topics: Adult; Antibodies, Monoclonal; Cornea; Corneal Diseases; Descemet Membrane; Endothelium; Female; Histocytochemistry; Humans; Immunochemistry; Iris Diseases; Keratins; Microscopy, Electron; Syndrome; Visual Acuity

A 26-year-old male patient with dermatological and systemic features suggestive of dyskeratosis congenita is reported with an unusual associated ocular feature of bilateral cataract.

Topics: Adult; Cataract; Humans; Keratins; Male; Pedigree; Skin Diseases; Syndrome

Histological, histochemical and immunohistochemical findings were studied in 40 cutaneous biopsies from 7 patients with Cowden's disease. Most facial biopsies showed a spectrum of trichilemmomas and related follicular malformations, including cylindrical trichilemmomas, lobulate trichilemmomas (14 lesions), and a keratinizing type sharing features with inverted follicular keratosis. One facial growth showed trichilemmomal changes without apparent follicular origin. Studies for common papilloma virus structural antigens were negative, apart from a typical common wart in one patient. Immunohistochemical studies in 6 facial trichilemmomas and acral keratoses, using a panel of anti-keratin antibodies, disclosed only abnormal differentiation with lack of large keratins in the lobulate trichilemmomas. Nine biopsies revealed a distinctive type of fibroma characterized by an organized pattern of interwoven fascicles of collagen bundles with a laminated or tortuous appearance, embedded in abundant mucin. A number of fibromas showed striking hyalinization; these may represent a second microscopic hallmark of Cowden's disease in addition to facial trichilemmomas.

Topics: Antigens, Viral; Biopsy; Facial Neoplasms; Fibroma; Hamartoma; Humans; Keratins; Skin; Skin Neoplasms; Staining and Labeling; Syndrome

Topics: Brain Diseases; Hair; Hair Diseases; Humans; Keratins; Syndrome

A Japanese girl, 2 years, 8 months of age, with palmoplantar keratosis and dendritic corneal opacities, showed increased tyrosine levels in the plasma, urine, and cerebrospinal fluid. The mental and physical growth was not retarded. The hepatorenal functions were within normal limits. Electron microscopically, the epidermal keratinocytes showed increased tonofibrils and no structures suggestive of tyrosine crystals. Cytosol and mitochondrial tyrosine aminotransferase (TAT) activities of the liver were greatly decreased, while p-hydroxyphenyl pyruvate oxidase (p-HPPO) activity was not decreased. The plasma tyrosine levels were controlled for 3 years with low phenylalanine-tyrosine diet.

Topics: Amino Acid Metabolism, Inborn Errors; Child, Preschool; Corneal Opacity; Female; Humans; Keratins; Keratoderma, Palmoplantar; Phenylacetates; Phenylalanine; Phenylpropionates; Phenylpyruvic Acids; Syndrome; Tyrosine; Tyrosine Transaminase

Three males with the X-linked disorder dyskeratosis congenita are described. Each suffered femoral fractures after minimal trauma with poor healing. Long bones showed coarse trabecular patterns of the metaphyses and small lucency areas in the diaphyses. Two of the males were retarded brothers who additionally showed intracranial calcifications.

Topics: Adolescent; Bone and Bones; Bone Diseases; Calcinosis; Female; Fractures, Bone; Humans; Intellectual Disability; Keratins; Male; Osteoporosis; Radiography; Sex Chromosome Aberrations; Skin Diseases; Skull; Syndrome; X Chromosome

The Sjögren-Larsson syndrome (SLS) is characterized by congenital ichthyosis, spastic dior tetraplegia and mental retardation. The inheritance is autosomal recessive. All 36 patients with SLS alive in Sweden in 1980 were studied with regard to ichthyosis. A slight or moderate generalized hyperkeratosis, less pronounced in the face, was already present at birth. Collodion-like membranes were never seen. The ichthyosis developed to its full extent during infancy. It was sometimes slight but most often moderate. Three types occurred in various combinations. The skin changes were concentrated in the neck, flexures and lower abdomen, in which regions the scales were often dark. The non-scaly hyperkeratosis produced characteristic and easily visible skin markings. Generalized erythema was rare, especially in adults. The DNA synthesis of the epidermis and the production of a horny layer were increased. Hair and nails were normal, as also was the ability to sweat.

Topics: Adolescent; Adult; Biopsy; Child; Child, Preschool; DNA; Female; Genes, Recessive; Humans; Ichthyosis; Infant, Newborn; Intellectual Disability; Keratins; Male; Middle Aged; Muscle Spasticity; Paralysis; Skin; Syndrome

In two Arab brothers presenting the characteristic clinical picture of epidermodysplasia verruciformis (EV), histological examination revealed large clear cells in the granular layer and uppermost part of the prickle cell layer of the epidermis. The report of this histological picture in two cases by other authors in the past had aroused considerable discussion as to the true diagnosis. The finding of large clear cells in our two confirmed cases of EV supports the opinion that this does not necessarily contradict the diagnosis of EV. Electron microscope investigation revealed groups of particles in the nuclei of a few keratinocytes in the granular layer which were compatible with papova virus particles. The changes seen in the clear cells support the theory of the viral etiology of EV. Ehe immunological studies showed intact humoral immunity but impaired cellular immunity.

Topics: Adolescent; Epidermis; Humans; Keratins; Male; Papillomaviridae; Polyomaviridae; Precancerous Conditions; Skin Diseases; Skin Neoplasms; Syndrome

Hereditary mucoepithelial dysplasia is an autosomal, dominantly inherited disorder affecting all of the orificial mucosa with cataracts, follicular keratosis of skin, nonscarring alopecia, bouts of pneumonia, spontaneous pneumothorax, and terminal cor pulmonale. The oral lesion is a fiery red, flat or micropapillary-appearing mucosa most frequently involving the gingiva and hard palate. All oral and pharyngeal mucosa may be involved, however. Red scrotal mucosa of the tongue is common. Histologically, the oral mucosa shows a lack of cornified and keratinized cells, a decrease in the thickness of the epithelial cell layer, dyshesion, and dyskeratosis. Papanicolaou smears show lack of epithelial cell maturation, poikilocytosis, anisocytosis, large paranuclear cytoplasmic vacuoles, and cytoplasmic strand-shaped inclusions. Ultrastructural features include a paucity of desmosomes, intercellular accumulations of amorphous material, cytoplasmic vacuoles, and paranuclear lesions with strands of material resembling gap junctions and desmosomes. The condition most likely represents a basic defect in gap junction and desmosome formation.

Topics: Adult; Cell Adhesion; Cytoplasm; Desmosomes; Epithelium; Female; Gingiva; Gingival Diseases; Humans; Inclusion Bodies; Infant; Intercellular Junctions; Keratins; Mouth Diseases; Mouth Mucosa; Mucous Membrane; Syndrome; Vacuoles

Electron microscopic analyses of lichen simplex chronicus Vidal (LSC) are reported. The submicroscopic organization is described. The frequent occurrence of collagen fibres directly juxtaposed to and contiguous with the lamina basalis seems to be a distinguishing feature of the LSC. Discontinuations in the lamina basalis are rarely indicated. A ubiquitous fragmentation and a certain paucity of tonofilamentous structure are present in cells preceding parakeratosis. There is an indubitable paucity of tonofilament-keratohyalin association. Mitochondria, endoplasmic reticulum and ribosomes are abundant. Odland bodies of type II are completely dominant. Parakeratosis and observed submicroscopically deficient or incomplete orthokeratosis are related to the numbers of defective Odland bodies. The keratinization of some acanthotic disorders is discussed.

Topics: Adult; Collagen; Epidermis; Humans; Keratins; Male; Middle Aged; Neurodermatitis; Syndrome

The rate and pattern of epidermal lipogenesis from [14C] glucose were measured in fifteen patients with psoriasis and three with lichen simplex, compared with twenty controls. In 'uninvolved' epidermis from psoriatic subjects the mean lipogenic rate was slightly raised, although the increase was not statistically significant. There was a positive correlation between overall lipogenic rate and the percentage of isotope appearing in free sterol, while the relative proportions of the other lipid classes were unchanged. By contrast, in control epidermis sterol percentage was negatively correlated with lipogenic rate. In psoriatic lesions total epidermal lipogenesis (per unit surface area) was raised compared with matched control 'uninvolved' epidermis. Also raised were percentage labelling of free sterol and of combined (free sterol and monoesters), and the free sterol: monoester ratio was increased. Similar findings were obtained with lesions of lichen simplex, suggesting that disturbed sterol metabolism may be a common feature in conditions of abnormal keratinization.

Topics: Adolescent; Adult; Aged; Esters; Female; Glucose; Humans; Keratins; Lipids; Male; Middle Aged; Neurodermatitis; Psoriasis; Skin; Sterols; Syndrome

Topics: Animals; Cells, Cultured; Cornea; Corneal Dystrophies, Hereditary; Cytoplasm; Cytoplasmic Granules; Glycosaminoglycans; Histocytochemistry; Keratins; Lysosomes; Macula Lutea; Microscopy, Electron; Rabbits; Syndrome

Topics: Acrodermatitis; Adolescent; Biopsy; Cell Membrane; Child; Cytoplasm; Endoplasmic Reticulum; Female; Herpesviridae Infections; Humans; Impetigo; Keratins; Male; Microscopy, Electron; Neutrophils; Skin; Skin Diseases, Infectious; Syndrome

Topics: Adult; Aged; Cell Nucleus; Diagnosis, Differential; Female; Fingers; Humans; Keratins; Male; Nails; Nails, Malformed; Syndrome

Topics: Adolescent; Adult; Carcinoma, Squamous Cell; Cell Membrane; Cell Nucleus; Child; Child, Preschool; Collagen; Cytoplasm; Female; Fibroblasts; Foot Dermatoses; Hand Dermatoses; Humans; Keratins; Keratosis; Leg; Male; Melanocytes; Microscopy, Electron; Middle Aged; Skin; Syndrome

Topics: Adult; Chromosome Aberrations; Chromosome Disorders; Darier Disease; Desmosomes; Hand; Humans; Hyalin; Ichthyosis; Keratins; Male; Nails, Malformed; Scleredema Adultorum; Skin; Sweating; Syndrome

Topics: Adolescent; Adult; Aged; Basophils; Calcinosis; Child; Child, Preschool; Citrulline; Epithelial Cells; Eyelid Neoplasms; Facial Neoplasms; Female; Granulation Tissue; Hair; Humans; Infant; Keratins; Male; Sex Factors; Skin Neoplasms; Staining and Labeling; Syndrome

Topics: Abnormalities, Multiple; Adult; Carcinoma, Basal Cell; Chromosome Aberrations; Chromosome Disorders; Creatinine; Female; Humans; Jaw Diseases; Keratins; Male; Meningioma; Metabolic Clearance Rate; Middle Aged; Odontogenic Cysts; Phosphates; Syndrome

Topics: Animals; Brain Diseases; Child; Copper; Deficiency Diseases; Growth Disorders; Hair; Humans; Intellectual Disability; Keratins; Proteins; Sheep; Syndrome; Wool

Topics: Cell Membrane; Child; Child, Preschool; Cytoplasmic Granules; Desmosomes; Ectodermal Dysplasia; Female; Hair; Humans; Ichthyosis; Keratins; Microscopy, Electron; Scalp Dermatoses; Skin; Syndrome

Topics: Adult; Bone Cysts; Carcinoma, Basal Cell; Diagnosis, Differential; Epidermal Cyst; Humans; Jaw Diseases; Keratins; Male; Ribs; Skin; Skin Neoplasms; Syndrome