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Keratitis‐ichthyosis‐deafness syndrome is a rare genetic disease presenting with cutaneous, ocular, and otic defects. This comprehensive review provides insight into the clinical presentations, highlighting the cutaneous manifestations including histopathology and treatment options. [ABSTRACT FROM AUTHOR]

Pathogenic sequence changes in mitochondrial DNA (mtDNA) are one of the most common causes of genetic hearing loss. We report an infant with palmoplantar hyperkeratosis, extrapalmoplantar cutaneous features and mitochondrial sensorineural hearing loss caused by the previously reported pathogenic NC_012920: m.7445A > G sequence change in the mitochondrial gene COX1 (COX1, MT-CO1). Next generation sequencing- based technology was key for the diagnosis and management of this patient. [ABSTRACT FROM AUTHOR]

A 70-year-old man, a known case of diabetes mellitus since 10 years ago, presented with lower limb swelling and dyspnea on exertion for one month and dysphagia to solids associated with early satiety for 2 weeks. The patient had palmoplantar keratosis (PPK), which was present since birth with a similar family history. The patient was admitted to rule out esophageal malignancy. Upper gastrointestinal gastroscopy revealed esophagitis and esophageal melanosis with gastric mucosal erythema. Biopsies samples were taken. Histopathological examination revealed reflux esophagitis and chronic active Helicobacter pylori gastritis with no evidence of malignancy. His symptoms improved following H. pylori eradication and treatment for coronary artery disease and heart failure. The patient was advised of regular follow-up as he had risk factors for the development of esophageal melanoma or squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive disorder that exhibits palmoplantar keratosis and early severe periodontitis. The oral disease affects both the primary and permanent dentitions leading to premature exfoliation of teeth. Various etiologic factors, such as genetic mutations, immunologic alterations, and bacteria have been implicated in PLS. Genetic mutations leading to the loss of function of cathepsin C (CTSC) gene, located on chromosome 11q14, is considered pivotal in this condition. The present case series describes PLS in three siblings, with consanguineously married parents, who live in a remote area of Yemen. The affected children presented with prominent palmoplantar keratosis and early periodontitis with only a few remaining teeth. The severity of skin lesions in all patients exhibited seasonal variations. Based on their clinical findings, a diagnosis of PLS was made. Dentists have a significant role in the early diagnosis and management of PLS patients. [ABSTRACT FROM AUTHOR]

Nagashima-type palmoplantar keratosis (NPPK) is a diffuse, non-syndromic (isolated), autosomal recessive palmoplantar keratoderma (PPK) with transgredients. It is characterized by non-progressive mild to moderate transgredient PPK. The mutation in SERPINB7 is reported to underlie the condition. Though many case reports/series have demonstrated various mutations in SERPINB7, the genotype-phenotype correlation in this disorder is still lacking. We herein report two brothers with NPPK. Both patients were found to be compound heterozygous for c.796C>T and c.650_653delCTGT in the SERPINB7 gene. We then summarize the previously reported cases of different mutations in SERPINB7 along with their clinical phenotypes in an attempt to shed some light on this correlation. Further investigations and systematic data collection are still needed to clarify this issue.

Papillon–Lefevre syndrome (PLS) is an autosomal recessive genetic disorder caused by a deficiency in Cathepsin C. It is characterized by palmoplantar keratosis and premature loss of both primary and permanent dentition. Patients are often edentulous at an early age. Other symptoms include increased susceptibility to infections. Various etiologic factors such as genetic mutations, immunologic alterations, and bacteria have been implicated. We present a case report of 12-year-old female who reported to the dental clinic with a history of pain and swollen gums. Family history revealed consanguinity. On clinical examination, there was palmoplantar keratosis and examination of the oral cavity showed generalized periodontal pockets, tooth mobility, and periodontal abscess. Radiographic examination revealed generalized horizontal bone loss. Lateral cephalogram revealed retarded somatic development. A diagnosis of PLS was arrived based on history, clinical and radiological findings. Nonsurgical periodontal treatment along with the treatment of skin lesions was performed. A combined and intensive mechanical and antimicrobial treatment with supportive periodontal treatment in PLS patients may halt the periodontal disease progression. The dentists should be aware of the same because an early diagnosis of the syndrome can help to preserve the teeth by the timely institution of treatment, using a multidisciplinary approach. [ABSTRACT FROM AUTHOR]

Nagashima-type palmoplantar keratosis (NPPK) is a diffuse, non-syndromic (isolated), autosomal recessive palmoplantar keratoderma (PPK) with transgredients. It is characterized by non-progressive mild to moderate transgredient PPK. The mutation in SERPINB7 is reported to underlie the condition. Though many case reports/series have demonstrated various mutations in SERPINB7, the genotype-phenotype correlation in this disorder is still lacking. We herein report two brothers with NPPK. Both patients were found to be compound heterozygous for c.796C>T and c.650_653delCTGT in the SERPINB7 gene. We then summarize the previously reported cases of different mutations in SERPINB7 along with their clinical phenotypes in an attempt to shed some light on this correlation. Further investigations and systematic data collection are still needed to clarify this issue. [ABSTRACT FROM AUTHOR]

Papillon-Lefèvre syndrome (PLS) is a rare genetic disorder characterized by palmoplantar keratosis and premature loss of primary and permanent dentition. Its onset can be as early as 1-4 years of age. The genetic disorder is mutation in the cathepsin C gene. Hereby, we discuss the fabrication of Cu-sil dentures for the prosthetic rehabilitation of a 14-year-old girl with PLS. The case report describes the procedure and associated relevant information regarding the management protocols. [ABSTRACT FROM AUTHOR]

Summary: Background: Mutations in the desmoplakin (DSP) gene have been demonstrated to be associated with lethal acantholytic epidermolysis bullosa, cardiomyopathy, and palmoplantar keratoderma (PPK). Aims: To better understand the relationship between PPK and the gene mutations in DSP. Methods: A pedigree of PPK was subjected to heterozygous missense mutation analysis in the DSP gene. Dermoscopy, reflectance confocal microscopy, and histopathological examination were performed from each epidermis layer in this study. Samples were derived from the blood of patients and normal healthy controls. DSP gene sequence analysis and Q‐PCR analysis was performed for evaluating DSP gene mutation and expression. Results: A novel heterozygous missense mutation c.3550 C>T in the coding region of the DSP gene, predicting substitution of arginine (Arg,R) by tryptophan (Trp,W) in the desmoplakin polypeptide, was discovered in a Chinese pedigree of PPK. In the meanwhile, this mutation was not found in 100 healthy individuals. Conclusions: The novel missense mutation c.3550 C>T(p.Arg1184Trp) of DSP gene expanded the mutation spectrum in palmoplantar keratoderma. [ABSTRACT FROM AUTHOR]

Premature tooth loss is a disastrous situation that affects deciduous or permanent teeth era with different causes. It may be attributed to some disorders like Papillon-Lefevre syndrome or coffin-lowry syndrome but because of ambiguous nature, precise diagnosis is not easily possible. Moreover, it has very low incidence and defines by few and limited case series, with vague characters to some extent, confusion in detecting the right diagnosis is a common possibility. Hence, it is expectable to have a wrong diagnosis for this case. In this study, a 5-yr-old boy with chief complaint of early tooth loss despite having blindness in left eye and palmar keratosis is reported, although he had some other manifestation of oculodentodigital dysplasia (ODDD) like ataxia, dysarthria and nail deformity, ignoring other extra and intra oral finding. He was diagnosed as Papillon-Lefevre syndrome already, just because of early tooth loss and palmar keratosis. [ABSTRACT FROM AUTHOR]

Background: Papillon–Lefèvre syndrome is a rare autosomal recessive disorder characterized by palmoplantar hyperkeratosis and aggressively progressing periodontitis leading to premature loss of deciduous and permanent dentition. The etiopathogenesis of the syndrome is relatively obscure, and immunologic, genetic, or possible bacterial etiologies have been proposed. Case presentation: A series of five cases of Papillon–Lefèvre syndrome among the siblings in a family is presented here: a 3-year-old Arab girl, a 4-year-old Arab boy, a 11-year-old Arab boy, a 12-year-old Arab boy, and a 14-year-old Arab boy. The patients presented with severe gingival inflammation and mobility of teeth. The clinical manifestations were typical of Papillon–Lefèvre syndrome and the degree of involvement of the oral and skin conditions varied among them. Conclusions: This case series stresses the consanguinity in the family as an etiologic factor. All siblings in the family were affected with Papillon–Lefèvre syndrome which makes this a rare case. A multidisciplinary approach with the active participation of a dental surgeon, dermatologist, and pediatrician is essential for the management of cases of Papillon–Lefèvre syndrome. [ABSTRACT FROM AUTHOR]

Papillon Lefevre syndrome (PLS) is an autosomal recessive disorder that results from a mutated gene that encodes a lysosomal peptidase known as cathepsin C (CTSC). The clinical presentation of PLS involves mainly palmoplantar keratosis and periodontitis with a variable degree of severity. and methods: Our study included ten patients with a broad spectrum of palmoplantar keratosis and periodontitis severity. CTSC variants were detected by Sanger sequencing. CTSC protein secreted in urine was detected by western blotting. Five patients have missense variants, Four have nonsense variants, and one has splice variants in CTSC. The activation products of cathepsin C protein (Heavy and light chains) were absent in all patients' urine samples except one with a significantly reduced level compared to the controls. The dimeric form of CTSC protein was found in all the studied cases. The monomeric form was found in five cases. The products of proteolytic activation of CTSC by other cathepsins (L and S) were found in the urine samples of five of the patients. Each patient had a characteristic pattern of accumulated CTSC protein maturation/activation substrates, intermediates, and products. 40% of the patients had the activation products of other lysosomal cathepsins. Urinary CTSC in PLS patients could be used as a diagnostic biomarker for the biochemical screening of the disease. Different variants in CTSC result in different profiles of CTSC secreted in the urine of PLS patients. The profiles of secreted CTSC in urine could be correlated to the severity of palmoplantar keratosis. • Cathepsin C (CTSC) protein secretion in urine diagnose Papillon Lefevre syndrome. • CTSC protein profile in urine varies among patients with Papillon Lefevre syndrome. • The type of mutation in CTSC affects the CTSC protein profile in urine. • Palmoplantar keratosis severity is correlated with CTSC protein profile in urine. [ABSTRACT FROM AUTHOR]

Haim-Munk syndrome is an extremely rare autosomal recessive disorder of keratinization characterized clinically by palmoplantar hyperkeratosis, severe early onset periodontitis, onychogryphosis, pes planus, arachnodactyly, and acro-osteolysis. Recently, germline mutations in the lysosomal protease cathepsin C gene have been identified as the underlying genetic defect in Haim-Munk syndrome and in the clinically related disorders, such as Papillon-Lefθvre syndrome and prepubertal periodontitis. The periodontal disease associated with these syndromes is particularly aggressive and unresponsive to traditional periodontal therapies. As a result, most patients become edentulous by 15 years of age. This case report describes a patient with the cardinal features of Haim-Munk syndrome.

RASopathies are rare genetic disorders caused by germline pathogenic variants in genes belonging to the RAS/MAPK pathway, which signals cell proliferation, differentiation, survival and death. The dysfunction of such signaling pathway causes syndromes with overlapping clinical manifestations. Skin and adnexal lesions are the cardinal clinical signs of RASopathies, such as cardiofaciocutaneous syndrome, Noonan syndrome with multiple lentigines, formerly known as LEOPARD syndrome, Costello syndrome, neurofibromatosis (NF1), Legius syndrome, Noonan-like syndrome with loose anagen hair (NSLH) and Noonan syndrome. As NF1, one of the most common RASopathies, described in 1882, has its clinical features well delineated, we will focus on the dermatological diagnosis, management and care of non-NF1 RASopathies, which are less known and more recently described. Dermatological manifestations are important clinical diagnostic elements that can aid differential diagnosis among RASopathies. They can affect dermis and epidermis, causing pigmented lesions (melanocytic nevi, café-au-lait spots, and lentigines), hyperkeratosis (keratosis pilaris, ulerythema ophryogenes, and palmoplantar keratosis) or hyperplasia. To date there are rare known links to malignancy, but oftentimes skin lesions require close attention because they can highly affect quality of life., (© 2022 Wiley Periodicals LLC.)

Papillion-Lefevre Syndrome is a rare autosomal recessive disorder characterized by severe early onset periodontopathia and palmoplantar hyperkeratosis leading to premature loss of primary and permanent dentition. PLS is caused by mutations in cathepsin C (CTSC) gene. It is transmitted with an estimated frequency of one to four per million individuals. In this case report, we present clinical and other relevant investigations of three siblings with symptoms typical of Papillion-Lefevre Syndrome. The three siblings were born of a second-degree consanguineous marriage, where the parents were first cousins. All the siblings reported with mobility, eventually leading to loss of teeth and masticatory inefficiency. All showed hyperkeratosis of palms and soles, with youngest sibling showing mild to severe form of severe generalized periodontal destruction. The elder two siblings were given dentures. The youngest sibling is undergoing periodontal therapy and has received partial dentures for missing teeth. [ABSTRACT FROM AUTHOR]

Mal de Meleda is a rare autosomal recessive genodermatosis caused by mutations in the ARS B ( SLURP1) gene, with possible founder effects in the Mediterranean and Adriatic regions. We report an affected individual from Indonesia without known consanguinity in the family, suggesting that SLURP1 gene mutations are ubiquitous. Recognition of the phenotype can be confirmed by genetic testing, thus facilitating genetic counselling. [ABSTRACT FROM AUTHOR]

The co-occurrence of two rare recessive genetic conditions in apparently unrelated individuals or families is extremely rare. Two geographically distant and apparently unrelated families were identified in which individuals were simultaneously affected by two rare recessive mendelian syndromes, Papillon–Lefèvre syndrome and type 1 oculocutaneous albinism. The families were tested for mutations in the causative genes, cathepsin C (CTSC) and tyrosinase (TYR), respectively, by direct sequencing. To assess the relationship of the two families, both families were tested for polymorphisms at eight microsatellite markers spanning bothCTSCandTYRloci. Independent mutations (c.318–1G→A and c.817G→C/p.W272C) were identified inCTSCandTYR, respectively, that were shared by the affected individuals in both families. The two affected genes lie close together on chromosome bands 11q14.2–14.3, and studies with linked genetic markers suggested that the families shared a small chromosomal segment carrying both mutations that had been transmitted intact from a remote common ancestor. The co-occurrence of the two rare diseases in multiple families depends on their shared chromosomal location, but not on any shared pathogenic mechanism. [ABSTRACT FROM AUTHOR]

We have followed a case of Papillon-Lefèvre syndrome over 20 years since the patient was brought to our hospital at the age of four. During this period, we inserted two sets of primary dentition dentures each into the upper and lower jaws, and later five sets of permanent dentition dentures in the both jaws corresponding the changes in the oral condition tootn erupution, exfoliation and the number of remaining teeth. From the longitudinal odservation, we have arrived at the conclusions as follows: [ABSTRACT FROM AUTHOR]

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 he a casual association in individuals with PPK. Genetic syndromes with palmoplantar keratosis and severe early 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-Leièvre syndrome were examined to determine disease status, and genotyped for microsatellite DNA markers closeIy 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 Maim 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. [ABSTRACT FROM AUTHOR]

Gap junction proteins are composed of 21 genes of the connexin (Cx) family. They play important roles in cell-cell contact by exchange of small molecules through hemichannels. Hence, mutations of Cx family genes affect various tissues of a body. The mutation of the GJA1 gene, which codes Cx43, causes oculodentodigital dysplasia ( ODDD), commonly in an autosomal dominant manner with phenotypic variability. It has been believed that gene mutations causing truncation of the Cx43 C-terminus is necessary and sufficient for palmoplantar keratosis ( PPK) development in ODDD patients. Here, we report a case of an ODDD patient developing PPK with a GJA1 gene mutation (c.412G>A/p.Gly138Ser), which was previously reported in a case of ODDD without PPK and expected not to result in C-terminal truncation of Cx43. This case suggests not only C-terminal truncation, but also that a point mutation in the cytoplasmic region of Cx43 can cause PPK in ODDD patients. [ABSTRACT FROM AUTHOR]

Richner-Hanhart syndrome (tyrosinemia type II) is a rare autosomal recessive disease associated with high serum tyrosine levels caused by the deficiency of tyrosine aminotransferase enzyme. We report a 15-year-old female patient with complaints of bilateral photophobia and tearing, which started during the infancy period. Biomicroscopic examination revealed bilateral circular corneal opacities on the inferior quadrant and small dendritic lesions at the center of the circular opacities. Blood tests showed a tyrosine level of 508 µmol/L (normal range: 30-150). On her dermatologic examination, plantar hyperkeratosis and seborrheic dermatitis were noted, and mild mental retardation was detected. One and a half months after the tyrosine- and phenylalanine-restricted diet, her tyrosine level dropped to 395 µmol/L level, her corneal lesions subsided, and a symptomatic relief was achieved. Tyrosinemia type II should be suspected in patients demonstrating dermatologic signs, especially palmoplantar keratosis, associated with bilateral pseudodendritic corneal lesions unresponsive to antiviral therapy. [ABSTRACT FROM AUTHOR]

Papillon-Lefevre Syndrome (PLS) is a very rare autosomal recessive disorder characterized by palmoplantar hyperkeratosis and severe early onset periodontitis, affecting the primary and permanent dentition. The syndrome was first described by Papillon and Lefevre in 1924. Genetic, immunologic, and microbiologic factors are suggested as responsible for the initiation and progression of the disease. A point mutation of cathepsin C gene has recently been detected in PLS. A multidisciplinary approach is important for management .The prognosis has improved with the early recognition of the syndrome, effective professional supervision, and home care. [ABSTRACT FROM AUTHOR]