Hyperkeratosis Of Palms Research Articles

Two siblings with triple A syndrome and novel mutation presenting as hereditary polyneuropathy

The clinical and molecular data on triple A syndrome in two siblings (girl 3.5years and boy 5.5years at presentation) with early onset of neurological dysfunction are described. Both patients showed delayed developmental milestones and neurological dysfunctions (motor and sensory demyelinating neuropathy, marked hyperreflexia, calves hypothrophy, pes cavus, gait disturbance) in early childhood, when erroneously diagnosed with hereditary polyneuropathy, most likely Charcot-Marie-Tooth disease. After a severe adrenal crisis in the younger sister at the age of 3years, the older brother aged 5.5years was also evaluated and latent adrenal insufficiency was discovered. As both of the siblings had alacrima, hyperkeratosis of palms, cutis anserina, and nasal speech, diagnosis of triple A syndrome was considered. Sequencing of the AAAS gene detected a compound heterozygous mutation consisting of a novel mutation p.Ser296Tyr (c.887C>A) in exon 9 and a previously described p.Ser263Pro (c.787T>C) missense mutation in exon 8 in both siblings. In conclusion, triple A syndrome should be considered in patients presenting with early neurological dysfunction and developmental delay. Alacrima as the earliest and most consistent clinical sign should be investigated by Schirmer test. Patients should be regularly tested for adrenal dysfunction to prevent life-threatening adrenal crises.

Treatment of Patient With Papillon-Lefevre Syndrome With Short Dental Implants: A Case Report

Papillon-Lefevre syndrome (PLS) is an autosomal recessive disorder. Main features of PLS are hyperkeratosis of palms and soles concomitant with premature loss of primary and permanent dentition due to progressive periodontitis. Dental management of patients with PLS is usually challenging because of early excessive loss of alveolar bone support. We describe dental rehabilitation of a 34-year-old patient with PLS with severely atrophic mandible by means of 2 short (6 mm) dental implants between 2 mental foramina supporting an implant retained complete denture. After 1 year of follow-up period, the patient was doing well and there was no sign of bone resorption. In patients with PLS, dental osseointegrated implants (even with shorter lengths) can be safely used for atrophic mandibles instead of invasive preprosthetic applications such as bone augmentation, nerve lateralization, or alveolar distraction to avoid possible complications.

Acne rosacea associated imatinib mesylate in a gastrointestinal stromal tumor patient

Tyrosine kinase inhibitors (TKIs) are targeted treatments for various cancers. Skin toxicities are one of the most common nonhematological side-effects of TKIs. We report an imatinib mesylate (IM) induced hyperpigmented acne rosacea (AR) and sunitinib-induced palmar hyperkeratosis in the case with gastrointestinal stromal tumor. AR was arisen due to the discontinuation of IM. To the best of our knowledge, this kind of cutaneous side-effect with IM has not been documented previously.

Papillon–Lefevre syndrome: A case report

Papillon-Lefevre syndrome (PLS) is a rare autosomal recessive disorder of keratinization, characterized by palmoplantar hyperkeratosis, periodontal involvement and precocious loss of dentition. The purpose of this report was to describe the case of an 18-year-old girl who presented to the out patient department of Navodaya Dental College and Hospital, Raichur, Karnataka, India, with the chief complaint of multiple loss of teeth. Her gingiva appeared erythematous, edematous and bled readily on probing, and the teeth were mobile. Hyperkeratosis of palms and soles were found. These findings are consistent with Papillon-Lefèvre syndrome. The clinical presentation, differential diagnosis, complications and management of this syndrome are discussed.

Papillon-Lefevre Syndrome

Papillon-Lefevre syndrome is a rare autosomal recessive disorder caused by cathepsin C gene mutation leading to the deficiency of cathepsin C enzymatic activity. The disease is characterized by palmoplantar hyperkeratosis, loss of deciduous and permanent teeth and increased susceptibility to infections. Onset of palmoplantar hyperkeratosis and periodontopathy is most commonly before the age of 4 years. A 15 year old boy with a history of frequent infections presented with hyperkeratosis of palms and soles, which worsened during winter season. Examination of the oral cavity revealed missing mandibular central incisors and left lateral incisors. Most remaining permanent teeth were mobile. Fibrosis and scarring of gingival and labial mucosa restricted opening of the mouth. Early diagnosis of Papillon-Lefevre syndrome may help preserve the teeth. We present a case of a late diagnosis of this syndrome.

Gorlin-Goltz syndrome: incidental finding on routine ct scan following car accident

IntroductionGorlin-Goltz syndrome is a rare hereditary disease. Pathogenesis of the syndrome is attributed to abnormalities in the long arm of chromosome 9 (q22.3-q31) and loss or mutations of human patched gene (PTCH1 gene). Multiple basal cell carcinomas (BCCs), odontogenic keratocysts, skeletal abnormalities, hyperkeratosis of palms and soles, intracranial ectopic calcifications of the falx cerebri and facial dysmorphism are considered the main clinical features. Diagnosis is based upon established major and minor clinical and radiological criteria and ideally confirmed by DNA analysis. Because of the different systems affected, a multidisciplinary approach team of various experts is required for a successful management.Case presentationWe report the case of a 19 year-old female who was involved in a car accident and found to present imaging findings of Gorlin-Goltz syndrome during a routine whole body computed tomography (CT) scan in order to exclude traumatic injuries.ConclusionRadiologic findings of the syndrome are easily identifiable on CT scans and may prompt to early verification of the disease, which is very important for regular follow-up and better survival rates from the co-existent diseases.

Síndrome tilose hereditária e câncer de esôfago

Tylosis palmoplantaris is an autosomal dominant disorder characterized by hyperkeratosis of palms and soles. Lesions start during childhood and are more evident in areas of pressure. Familial tylosis palmoplantaris comprises two forms: epidermolytic and non-epidermolytic. Patients with the epidermolytic variant have up to 40% higher chance of developing squamous cell carcinoma of the esophagus. The association of tylosis palmoplantaris with esophageal cancer is called Howel-Evans syndrome.

Epidermolysis Bullosa Simplex Dowling-Meara - A case report

A case with Epidermolysis bullosa simplex DowlingMeara is presented. It concerns a 20 days breast-fed girl with severe blistering and erosions on the skin formed at birth after minor mechanical trauma. There are no other affected relatives. A medical examination showed normal somatic and visceral status. There were multiple herpetiform grouped bullous and erosive lesions on the face, trunk, upper and lower limbs, palms and soles. The mucous membranes were not affected. There was also a marked nail dystrophy on the fingers and toenails. The electron microscopic examination revealed cytolysis of the basal keratinocytes with clumping of the perinuclear tonofilaments in the lesional skin. Because of the clinical features and the results of the electron microscopic examination of the skin the case here reported should be considered as an Epidermolysis bullosa simplex DowlingMeara. The child is followed up to the age of three. The course of the disease was benign with a decreased formation of blisters and erosions. The marked nail dystrophy was persistent. There was palmar and plantar hyperkeratosis. The child’s growth, neural and psychic development was normal. The early diagnosis of the bullous epidermolysis is helpful in the prognostic assessment of the disease and in the medical and genetic advice for the parents.

Nevoid basal cell carcinoma syndrome (Gorlin syndrome)

Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is a hereditary condition characterized by a wide range of developmental abnormalities and a predisposition to neoplasms.The estimated prevalence varies from 1/57,000 to 1/256,000, with a male-to-female ratio of 1:1.Main clinical manifestations include multiple basal cell carcinomas (BCCs), odontogenic keratocysts of the jaws, hyperkeratosis of palms and soles, skeletal abnormalities, intracranial ectopic calcifications, and facial dysmorphism (macrocephaly, cleft lip/palate and severe eye anomalies). Intellectual deficit is present in up to 5% of cases. BCCs (varying clinically from flesh-colored papules to ulcerating plaques and in diameter from 1 to 10 mm) are most commonly located on the face, back and chest. The number of BBCs varies from a few to several thousand. Recurrent jaw cysts occur in 90% of patients. Skeletal abnormalities (affecting the shape of the ribs, vertebral column bones, and the skull) are frequent. Ocular, genitourinary and cardiovascular disorders may occur. About 5–10% of NBCCS patients develop the brain malignancy medulloblastoma, which may be a potential cause of early death.NBCCS is caused by mutations in the PTCH1 gene and is transmitted as an autosomal dominant trait with complete penetrance and variable expressivity.Clinical diagnosis relies on specific criteria. Gene mutation analysis confirms the diagnosis. Genetic counseling is mandatory. Antenatal diagnosis is feasible by means of ultrasound scans and analysis of DNA extracted from fetal cells (obtained by amniocentesis or chorionic villus sampling). Main differential diagnoses include Bazex syndrome, trichoepithelioma papulosum multiplex and Torre's syndrome (Muir-Torre's syndrome).Management requires a multidisciplinary approach. Keratocysts are treated by surgical removal. Surgery for BBCs is indicated when the number of lesions is limited; other treatments include laser ablation, photodynamic therapy and topical chemotherapy. Radiotherapy should be avoided. Vitamin A analogs may play a preventive role against development of new BCCs.Life expectancy in NBCCS is not significantly altered but morbidity from complications can be substantial. Regular follow-up by a multi-specialist team (dermatologist, neurologist and odontologist) should be offered. Patients with NBCCS should strictly avoid an excessive sun exposure.

Novel and recurrent mutations in the 1B domain of keratin 1 in palmoplantar keratoderma with tonotubules

Conflicts of interest: none declared. Palmoplantar keratodermas (PPKs) are a large group of disorders characterized by hyperkeratosis of palms and soles. They can be classified by their mode of inheritance, the morphology and distribution of the hyperkeratosis (diffuse, focal or punctate), the involvement of other ectodermal structures, the presence or absence of associated nonectodermal features and the morphological findings at light and electron microscopic levels.1 Mutations in a variety of proteins are associated with different types of PPK. These proteins include keratins, proteins of the cornified cell envelope (loricrin), and molecules for cohesion (desmoglein, desmoplakin), intercellular communication (connexins) and transmembrane transduction (cathepsin C). PKK of Voerner is the most frequently inherited PPK.2 It is transmitted in an autosomal dominant mode and starts within the first year of life. It is characterized by a diffuse, yellowish or erythematous hyperkeratosis, sometimes covering bullous lesions, that is sharply demarcated with an erythematous margin; typically there is no progression to the dorsal aspects of hands and feet. Additional features frequently seen are knuckle pad‐like keratoses over the flexural areas of the finger joints, clubbing of the nails, and hyperhidrosis.3 Mutations in the keratin 9 gene (KRT9) have been identified in this PPK.3

Letters to the Editor

4 October 2007 Dear Sir, PACHYONYCHIA CONGENITA Pachyonychia congenita is a rare genodermatosis which is autosomal dominant in inheritance. We describe a Malay toddler who presented with leukaemia and this condition. A 20-month-old Malay boy was referred to our hospital for the management of acute lymphoblastic leukaemia. He had been noted to have abnormal nails at infancy and had been initially diagnosed to have onychomycosis. His nail clippings grew Aspergillus niger and he had been treated with itraconazole for several months. However, there was no improvement in the condition of his nails. He was then labelled as having yellow-nail syndrome. On examination at our centre, he was found to have hyperpigmentation and hyperkeratosis of all his fingernails as well as toenails. His mother had similar findings (Fig. 1) and she also had hyperkeratosis of her soles. No one else in the family was affected. Apart from the nail changes, the child did not have any oral lesions and his palms and soles were also normal. A diagnosis of pachyonychia congenita type 1 was made clinically and his mother was counselled regarding the disease. The child has completed two years of chemotherapy without complications and is currently well and in remission. Hyperpigmentation and hyperkeratosis of all 10 fingernails of both mother and child. Classic type 1 pachyonychia congenita (Jadassohn–Lewandowski syndrome) is due to mutations in the gene for keratin 16. It can cause a variety of ectodermal defects affecting the nails, skin, oral mucosa, larynx, hair and teeth.1 Nail dystrophy is the most striking feature, with thickened, tubular nails which can present either at birth or early in life as in our patient. The second most prominent feature is palmoplantar keratoderma, which was present in this child's mother. Other features include onychogryphosis, follicular keratosis and oral leucoplakia. Type 2 pachyonychia congenita is characterised by natal teeth and the development of epidermal cysts or steatocysts. Onychomycosis is also a cause of hyperkeratosis. However, it rarely affects all 20 nails. The most common cause of tinea unguium is the dermatophyte Trichophyton rubrum. In Malaysia, it has been found that moulds, in particular Aspergillus niger, cause a significant proportion (35%) of onychomycosis.2 The yellow nail syndrome is a triad of thickened, excessively curved, slow-growing yellow nails, primary lymphoedema and chronic respiratory disease. It has previously been classified as a dominantly inherited condition with variable expressivity. However, this has been challenged recently by findings that suggest that the majority of cases are sporadic and that the nail changes may remit.3 Our patient had no previous medical history of note; he had never had lymphoedema or respiratory problems. The yellow nail syndrome is known to be associated with malignancies, in particular Non-Hodgkin's lymphomas and carcinomas.4 In contrast, pachyonychia congenita has not been associated with cancers although squamous cell carcinoma has been reported in a patient who had chronic plantar ulcerations.5 It is likely that the leukaemia in our patient was a chance association. The treatment of pachyonychia congenita consists of keratolytic agents and lubricants for the palmar and plantar hyperkeratosis. At present, there is no satisfactory treatment for the nail changes.

Papillon-Lefevre syndrome: Report of two cases in the same family

Papillon-Lefevre syndrome is a very rare syndrome of autosomal recessive inheritance characterized by palmar-plantar hyperkeratosis and early onset of a severe destructive periodontitis, leading to premature loss of both primary and permanent dentitions. Various etiopathogenic factors are associated with the syndrome but a recent report has suggested that the condition is linked to mutations of the cathepsin C gene. Two cases of Papillon-Lefevre syndrome in the same family, having all of the characteristic features, are presented. An 11-year-old girl and a 9-year-old boy presented with the complaints of loose teeth. Both expressed hyperkeratosis of palms, soles, and knees. Severe generalized periodontal destruction, with mobility of teeth, was evident on intraoral examination; orthopantomograph examination showed severe generalized loss of alveolar bone in both the patients.

Abstracts

Kindler syndrome (KS) is a rare disorder leading to keratinocyte fragility, poikiloderma and palmar hyperkeratosis (OMIM173650). Defects in the actin/focal contact associated protein kindlin-1 encoded by the gene KIND1 have been shown to underlie this disease. We assessed the function of kindlin-1 in human keratinocytes and fibroblasts using RNAi knockdown. RNAi treatment reduced KIND1 message by 72% and 63% in cultured keratinocytes and fibroblasts, respectively. RNAi treatment reduced cultured keratinocyte but not fibroblast cell adhesion to plastic. Furthermore, kindlin-1 depletion reduced keratinocyte (but not fibroblast) survival by increasing rates of adherent keratinocyte apoptosis, as detected by TUNEL staining. Kindlin-1 depleted keratinocytes demonstrated an initial delay in cell spreading and filopodia formation (as observed by scanning EM) but were associated with some focal adhesion / contact assembly (as visualized by vinculin staining). Keratinocyte (but not fibroblast) migration was increased after kindlin-1 depletion. Taken together our data suggest that kindlin-1 plays important roles in keratinocyte cell-substrate adhesion, spreading, migration and in keratinocyte survival in vitro. These observations may explain the loss of keratinocyte-basement membrane adhesion in the pathogenesis of KS induced skin fragility. Furthermore, reductions in keratinocyte survival and/or increased rates of apoptotic cell death may underlie the early-onset poikiloderma observed in KS cases.

Skin changes in oculo‐dento‐digital dysplasia are correlated with C‐terminal truncations of connexin 43

Oculo-dento-digital dysplasia (ODDD, OMIM no.164210) is a pleiotropic disorder caused by mutations in the GJA1 gene that codes for the gap junction protein connexin 43. While the gene is highly expressed in skin, ODDD is usually not associated with skin symptoms. We recently described a family with ODDD and palmoplantar keratoderma. Interestingly, mutation carriers had a novel dinucleotide deletion in the GJA1 gene that resulted in truncation of part of the C-terminus. We speculated, that truncation of the C-terminus may be uniquely associated with skin disease in ODDD. Here, we describe a patient with ODDD and palmar hyperkeratosis caused by a novel dinucleotide deletion that truncates most of the connexin 43 C-terminus. Thus, our findings support the notion that such mutations are associated with the occurrence of skin symptoms in ODDD and provide the first evidence for the existence of a genotype-phenotype correlation.

Periodontal therapy in siblings with Papillon–Lefèvre syndrome and tinea capitis: a report of two cases

Report of clinical and microbiological periodontal findings before and 6 months after treatment of two siblings with Papillon-Lefèvre syndrome (PLS) and tinea capitis. Two brothers, RG 3 years and NG 5 years of age, were referred for treatment due to premature mobility of their deciduous teeth. Probing depths (PPD), attachment levels (PAL-V), and furcation involvements were examined clinically. Panoramic radiographs were taken. Subgingival plaque samples within the deepest pocket of each tooth were taken and analysed by real-time polymerase chain reaction (PCR) for Actinobacillus actinomycetemcomitans (AA), Porphyromonas gingivalis, Tannerella forsythensis, Treponema denticola, Fusobacterium nucleatum, and Prevotella intermedia. One-stage full-mouth scaling and extraction of hopeless teeth were performed under general anaesthesia, followed by systemic amoxicillin and metronidazole for 7 days. Clinical and microbiological analyses were performed 6 months after treatment. Before treatment, both siblings had exhibited PPD of up to 13 mm, Class III furcation defects at four teeth, and marginal suppuration. AA was detected in both patients and at all teeth at levels ranging from 3.0 x 10(2) to 5.1 x 10(6). Both patients exhibited palmar and plantar hyperkeratosis. Seven teeth were extracted from RG, and nine from NG. Six months after treatment, PPD had been reduced to <or=5 mm. AA was not detected in any of the remaining teeth. Even periodontally affected deciduous teeth of PLS patients can be treated successfully. Suppression of AA to below detection level seems to be of high significance.

The IGF system in a case of Costello syndrome

Costello syndrome is characterized by facial dysmorphia, hyperpigmented skin, palmar and plantar hyperkeratosis, curly hair, perioral and nasal papillomata (more rarely localized anally and on vocal cords), short stature, mental retardation and sociable personality. Although growth retardation is typical of Costello syndrome, its cause is not defined. We report on a 10-yr-old Caucasian girl affected by Costello syndrome with fasting hypoglycemia and short stature, associated low circulating levels of acid-labile subunit (ALS), relatively low levels of IGF-I and IGFBP-3, and normal IGF-II, mostly circulating in a binary complex with IGFBP-2 and -6 instead of in a 150 kDa ternary complex. The reduced ALS concentration and the consequent impaired formation of the circulating 150 kDa ternary complex can induce an accelerated clearance rate of IGF peptides and of IGFBP-3, contributing to the decreased IGF-I growth promoting activity in our patient. Moreover, the presence of IGF-II in the binary complex, which has been postulated to increase the insulin-like effects of these peptides, can explain, at least in part, the patient's asymptomatic fasting hypoglycemia.

Compound Heterozygosity for New Splice Site Mutations in the Plakophilin 1 Gene ( PKP1) in a Chinese Case of Ectodermal Dysplasia–Skin Fragility Syndrome

Ectodermal dysplasia-skin fragility syndrome is a rare autosomal recessive inherited disease characterized by skin fragility, nail dystrophy and hyperkeratosis of palms and soles. Skin biopsy shows the loss of cell adhesion and the decrease of desmosomes in number and size. Mutations in PKP1 have been found to be the underlying cause of the syndrome. We report here a Chinese case of ectodermal dysplasia-skin fragility syndrome. Mutation analysis revealed compound heterozygosity for mutations in PKP1 of the proband. A new splice site mutation (c.1053 T>A+c.1054+1 G>T) near the 3' end of exon 5 and at the donor end of intron 5 on one allele was transmitted from the proband's mother. Another new splice site mutation (c.1835-2 A>G) near the acceptor end of intron 10 originated from her father. The absence of the mutant mRNA and plakophilin 1 protein in the proband's skin may result from the mechanism of nonsense-mediated mRNA decay induced by premature stop codons in PKP1 transcripts due to the two splice site mutations.

Focal palmoplantar and gingival keratosis: A distinct palmoplantar ectodermal dysplasia with epidermolytic alterations but lack of mutations in known keratins

Focal palmoplantar and gingival keratosis is a rare autosomal dominant disease whose clinical features, and in particular, pathologic alterations and molecular etiology remain to be well defined. Recently we observed a German family affected by the disease in at least 3 consecutive generations. The 4 patients examined showed circumscribed and painful hyperkeratosis at the weight-bearing plantar skin since infancy, rather mild palmar hyperkeratosis, and continuous leukokeratosis confined to the maxillary and mandibulary attached gingiva. There were no nail changes, subungeal keratoses, or follicular hyperkeratosis. Light and electron microscopy of the plantar and gingival lesions revealed alterations of epidermolytic hyperkeratosis. Mutations in the known keratin genes were excluded by linkage analysis using microsatellite markers. We conclude that focal palmoplantar and gingival keratosis is a clinically distinct palmoplantar ectodermal dysplasia that is pathologically characterized by epidermolytic alterations, but is most probably not caused by a mutation in a keratin gene.

Late-onset Papillon-Lefèvre syndrome without alteration of the cathepsin C gene

Mutations in the cathepsin C gene have recently been detected in Papillon-Lefèvre syndrome (PLS). Until now, 5 cases with the late-onset variation of this disease have been reported in the literature. The genetic background of this type of PLS is still unknown. We describe a 46-year-old woman with late-onset transgredient palmar hyperkeratosis and a 10-year history of severe periodontal disease. Histology of skin biopsy specimens revealed a psoriasiform pattern. Dental examination showed severe gingival inflammation with loss of alveolar bone. Dental plaque investigated by a polymerase chain reaction method revealed DNA signals of 5 different dental bacteria. DNA from EDTA blood was investigated for mutations in the cathepsin C gene by polymerase chain reaction analysis and direct sequencing. A silent variation in the codon for proline-459 was detected but interpreted as a polymorphism of this gene. All genetic linkage and mutation studies for PLS performed so far have shown that PLS is genetically homogeneous. Our patient with late-onset variation of PLS, however, did not show a mutation in the cathepsin C gene. Thus, we suspect that there is another genetic cause for the late-onset forms of PLS.

Sjögren-Larsson-Syndrom mit reduzierter Fettaldehyddehydrogenase-Aktivität bei einem Kollodiumbaby und konsanguinen Eltern

Sjoegren-Larsson Syndrome (SLS) is a rare autosomal recessive disorder characterized by ichthyosis after birth, spastic di- or tetraplegia, mental retardation and complete or incomplete reduction in fatty aldehyde dehydrogenase (FALDH) activity, the gene localized on chromosome 17p11.2. Three days after birth we saw a collodium baby of consanguine parents with erythrodermia and hyperkeratosis of palms and soles. In the age of 3,5 the boy developed a spastic of the leg, mental retardation, hyperkeratosis and desquamation in the neck, flank and flexural parts of the body. A biopsy at the age of 8 years revealed acanthosis, a reduced stratum granulosum and a hyperkeratotic puffed up stratum corneum. Electromicroscopy showed an intact stratum spinosum, intact hyaline granules in stratum granulosum, a partially irregular drop out of keratinosomes, no lipid droplets, no cholesterin gaps and no membrane staples. Enzymatic analysis of fibroblast cultures from the boy resulted in reduced FALDH-activity. Mutation analysis in lymphocytes showed homozygous complex mutations with the transversion 901G→C and a nucleotide deletion 906delT. The same complex mutation was found in the heterozygote state in father and mother. This is the second report about this complex mutation in the FALDH cDNA in SLS.