Ectodermal Dysplasia-skin Fragility Research Articles

Ectodermal Dysplasia-Skin Fragility Syndrome in an Infant

Ectodermal Dysplasia-Skin Fragility Syndrome in an Infant

Twisted tressess: a rare case series of familial woolly hair

Woolly hair is an uncommon congenital anomaly of the scalp hair presenting with strongly coiled hair involving a localized area of the scalp or covering the entire side and occurring in non-black people. Among the syndromes presenting with woolly hair, the most known are the Naxos syndrome, the Carvajal-Huerta syndrome, the woolly hair/hypotrichosis, the ectodermal dysplasia-skin fragility and the tricho-hepato-enteric syndrome. Case characteristics: herein, we report a case of autosomal recessive familial woolly hair of an Asian female child and member of a family, her younger brother affected by a localised woolly hair, not associated to complications. Children with woolly hair must be examined completely and monitored regularly to rule out cardiofaciocutaneous and Noonan syndrome.

Clinical spectrum of woolly hair: indications for cerebral involvement

BackgroundWoolly Hair is an uncommon congenital anomaly of the scalp hair presenting with strongly coiled hair involving a localized area of the scalp or covering the entire side and occurring in non-black people. Isolated or localized wooly hair is usually benign and is not related to other disorders and/or complications. On the contrary, the generalized type may be related to disorders and syndromes affecting heart, cutis, liver and gastrointestinal organs. Among the syndromes presenting with wooly hair, the most known are the Naxos syndrome, the Carvajal-Huerta syndrome, the wooly hair/hypotrichosis, the ectodermal dysplasia-skin fragility, the tricho-hepato-enteric syndrome.Case presentationTo our knowledge, no cases of wooly hair syndromes has been associated to neurologic involvement. Among the clinical notes of patients admitted in the Pediatric Units of the Catania University, we have selected four individuals presenting wooly hair, who showed different clinical features and course: case 1 presenting with a localized wooly hair type; case 2, member of a family affected by WH with autosomal dominant inheritance, not associated to complications; case 3, a wooly hair patient who displayed a progressive, severe form of Rasmussen’s encephalitis with fatal evolution, and case 4, wooly hair associated to brain malformation and drug-resistant epilepsy.ConclusionsWith this report, we aim to underline the wide spectrum of clinical presentation of individuals with WH and in particular we wish to give an annotation on a possible association of WH with severe neurologic disorders.

Ectodermal Dysplasia-Skin Fragility Syndrome: A Rare Case Report.

Ectodermal dysplasia/skin fragility syndrome (ED-SFS) is a newly described autosomal recessive disorder characterized by skin fragility and blistering, palmoplantar keratoderma, abnormal hair growth, nail dystrophy, and occasionally defective sweating. It results from mutations in the PKP1 gene encoding plakophilin 1 (PKP1), which is an important component of stratifying epithelial desmosomes and a nuclear component of many cell types. Only 12 cases of this rare genodermatosis have been reported so far. We present an unusual case of ED-SFS in a 12-year boy who was normal at birth but subsequently developed skin fragility, hair and nail deformities, abnormal dentition, palmoplantar keratoderma, and abnormal sweating but no systemic abnormality.

Ectodermal dysplasia-skin fragility syndrome: a novel mutation in thePKP1gene

Ectodermal dysplasia-skin fragility syndrome (EDSFS) is an autosomal recessive genodermatosis characterized by skin fragility, palmoplantar hyperkeratosis, onichodystrophy, perioral fissuring and noncicatricial alopecia. It is caused by plakophilin-1 (PKP1) deficiency, which results in desmosomal abnormality and poor intercellular cohesion between the epidermal cells. We report a case with a novel PKP1 mutation in intron 6.

Deficient Plakophilin-1 Expression Due to a Mutation in PKP1 Causes Ectodermal Dysplasia-Skin Fragility Syndrome in Chesapeake Bay Retriever Dogs

In humans, congenital and hereditary skin diseases associated with epidermal cell-cell separation (acantholysis) are very rare, and spontaneous animal models of these diseases are exceptional. Our objectives are to report a novel congenital acantholytic dermatosis that developed in Chesapeake Bay retriever dogs. Nine affected puppies in four different litters were born to eight closely related clinically normal dogs. The disease transmission was consistent with an autosomal recessive mode of inheritance. Clinical signs occurred immediately after birth with superficial epidermal layers sloughing upon pressure. At three month of age, dogs exhibited recurrent superficial skin sloughing and erosions at areas of friction and mucocutaneous junctions; their coat was also finer than normal and there were patches of partial hair loss. At birth, histopathology revealed severe suprabasal acantholysis, which became less severe with ageing. Electron microscopy demonstrated a reduced number of partially formed desmosomes with detached and aggregated keratin intermediate filaments. Immunostaining for desmosomal adhesion molecules revealed a complete lack of staining for plakophilin-1 and anomalies in the distribution of desmoplakin and keratins 10 and 14. Sequencing revealed a homozygous splice donor site mutation within the first intron of PKP1 resulting in a premature stop codon, thereby explaining the inability to detect plakophilin-1 in the skin. Altogether, the clinical and pathological findings, along with the PKP1 mutation, were consistent with the diagnosis of ectodermal dysplasia-skin fragility syndrome with plakophilin-1 deficiency. This is the first occurrence of ectodermal dysplasia-skin fragility syndrome in an animal species. Controlled mating of carrier dogs would yield puppies that could, in theory, be tested for gene therapy of this rare but severe skin disease of children.

Ectodermal dysplasia‐skin fragility syndrome due to a new homozygous internal deletion mutation in the PKP1 gene

Ectodermal dysplasia-skin fragility syndrome (ED-SFS) is a rare autosomal recessive genodermatosis resulting from mutations in the PKP1 gene, encoding the desmosomal plaque protein plakophilin-1 (PKP1). Mutations in PKP1 may manifest with skin fragility and erosions, patches of scale crust on the trunk and limbs, peri-oral cracking and inflammation, hypotrichosis, palmoplantar keratoderma with painful fissuring and other somewhat variable ectodermal anomalies. Ten cases of the syndrome have been reported. We report a further case of this desmosomal genodermatosis. A 14-month old child, born to consanguineous parents, presented with a history of neonatal bullae and subsequent development of dystrophic nails, sparse eyelashes and eyebrows, woolly scalp hair, abnormal dental development and a desquamating erythematous rash at sites of trauma. A clinical diagnosis of ED-SFS was supported by skin biopsy findings of suprabasal intraepidermal clefting and a loss of immunoreactivity for PKP1. Sequencing of genomic DNA revealed a homozygous 5 base pair deletion in exon 5 of the PKP1 gene, designated c.897del5 (CAACC). This new mutation creates a frameshift, leading to a downstream premature termination codon, p.Pro299fsX61. This case highlights the clinicopathological consequences of inherited mutations in the PKP1 gene and illustrates the key role of desmosomes in skin biology.

Ectodermal dysplasia-skin fragility syndrome

Ectodermal dysplasia-skin fragility (EDSF) syndrome is a rare and first described inherited disorder of desmosomes. It occurs due to loss-of-function mutations in PKP1 gene resulting in poorly formed desmosomes and loss of desmosomal and epidermal integrity. We report a case of a 2-year-old Indian male child who presented with palmoplantar hyperkeratosis with fissuring, short, sparse, and easily pluckable scalp hair, nail dystrophy, and multiple erosions over the skin. Skin biopsy showed epidermal hyperplasia with widening of intercellular spaces. His developmental milestones were delayed but intelligence was normal. Echocardiography, X-ray chest, and electrocardiogram were normal. Very few cases of this syndrome have been reported in the literature. We consider this as the first case report from India.

Ectodermal Dysplasia-Skin Fragility Syndrome

Pathogenic mutations have now been described in ten different desmosomal proteins: plakophilin 1 (PKP1) and 2 (PKP2); desmoplakin; plakoglobin; desmoglein 1, 2, and 4; desmocollin 2, and 3 corneodesmosin. Nevertheless, the first report of an inherited desmosomal gene disorder, published in 1997, involved loss-of-function mutations on both alleles of PKP1, the PKP1 gene. Loss of PKP1 expression in human skin leads to skin erosions and crusting, notably with perioral fissuring as well as palmoplantar hyperkeratosis with painful cracking of the skin. Other more variable features include abnormalities of ectodermal development with growth delay, hypotrichosis or alopecia, hypohidrosis, and nail dystrophy. In contrast to some other inherited disorders of desmosomes, there is no cardiac pathology in individuals with PKP1 mutations since it is not expressed in the heart. The collection of clinical features in individuals with PKP1 mutations has been termed ectodermal dysplasia-skin fragility (ED-SF) syndrome. This genodermatosis is classified as a suprabasal form of epidermolysis bullosa simplex and thus far there have been 10 published cases. Skin biopsy shows acanthosis, acantholysis, and a reduced number of small, poorly formed desmosomes. Loss of PKP1 expression results in an integral weakness within the desmosomal plaque, leading to desmosomal detachment and cell-cell separation. Thus, the clinicopathologic features attest to the significant role of PKP1 in stabilization of desmosome structure and function, predominantly in the spinous layers of the epidermis. This article reviews the clinical, structural, and molecular pathology of this genetic disorder of desmosomes.

The Desmosomal Plaque Proteins of the Plakophilin Family

Three related proteins of the plakophilin family (PKP1_3) have been identified as junctional proteins that are essential for the formation and stabilization of desmosomal cell contacts. Failure of PKP expression can have fatal effects on desmosomal adhesion, leading to abnormal tissue and organ development. Thus, loss of functional PKP 1 in humans leads to ectodermal dysplasia/skin fragility (EDSF) syndrome, a genodermatosis with severe blistering of the epidermis as well as abnormal keratinocytes differentiation. Mutations in the human PKP 2 gene have been linked to severe heart abnormalities that lead to arrhythmogenic right ventricular cardiomyopathy (ARVC). In the past few years it has been shown that junctional adhesion is not the only function of PKPs. These proteins have been implicated in cell signaling, organization of the cytoskeleton, and control of protein biosynthesis under specific cellular circumstances. Clearly, PKPs are more than just cell adhesion proteins. In this paper we will give an overview of our current knowledge on the very distinct roles of plakophilins in the cell.

Acantholytic ectodermal dysplasia: clinicopathological study of a new desmosomal disorder

We describe two boys with curly hair, palmoplantar keratoderma and skin fragility who presented clinical and histological features similar, but not identical, to those exhibited by patients with ectodermal dysplasia-skin fragility syndrome (McGrath syndrome) and other genetic desmosomal defects such as Carvajal syndrome and Naxos disease. Clinical features included trauma-induced blisters and erosions, palmoplantar keratoderma and hyperkeratotic, fissured plaques with perioral involvement. The patients had abundant curly scalp hair, and normal eyebrows and eyelashes. Sweating was normal. Nails were normal at birth but subsequently showed secondary dystrophy. Histopathological analysis of the skin demonstrated acantholysis and intercellular widening of the spinous and granular layers in involved regions. No involvement of scalp skin was seen. Desmosomes were markedly reduced in number and poorly developed with no clear insertions of the keratin filaments. The latter were clumped around the nuclei. Immunostaining of patient skin with antibodies raised against key desmosomal proteins demonstrated disrupted expression of desmoplakin, plakoglobin and desmoglein 1. Additional studies of the family history and of the desmoplakin, plakoglobin and desmoglein 1 genotype for both patients may help further elucidate the molecular cause of this variation on ectodermal dysplasia-skin fragility syndrome.

Novel truncating mutations inPKP1andDSPcause similar skin phenotypes in two Brazilian families

Inherited mutations in components of desmosomes result in a spectrum of syndromes characterized by variable abnormalities in the skin and its appendages, including blisters and erosions, palmoplantar hyperkeratosis, woolly hair or hypotrichosis and, in some cases, extracutaneous features such as cardiomyopathy. We investigated the molecular basis of two Brazilian patients presenting with clinical features consistent with ectodermal dysplasia-skin fragility syndrome. In patient 1 we identified a homozygous nonsense mutation, p.R672X, in the PKP1 gene (encoding plakophilin 1). This particular mutation has not been reported previously but is similar to the molecular pathology underlying other cases of this syndrome. In patient 2 we found compound heterozygosity for two frameshift mutations, c.2516del4 and c.3971del4, in the DSP gene (encoding desmoplakin). Although there was considerable clinical overlap in the skin and hair abnormalities in these two cases, patient 2 also had early-onset cardiomyopathy. The mutation c.3971del4 occurs in the longer desmoplakin-I isoform (which is the major cardiac transcript) but not in the more ubiquitous desmoplakin-II. In contrast, PKP1 is not expressed in the heart, which accounts for the lack of cardiomyopathy in patient 1. Collectively, these cases represent the first desmosomal genodermatoses to be reported from Brazil and add to genotype-phenotype correlation in this group of inherited disorders. Loss-of-function mutations in the DSP gene can result in a phenotype similar to ectodermal dysplasia-skin fragility syndrome resulting from PKP1 mutations but only DSP pathology is associated with cardiac disease.

Ectodermal dysplasia–skin fragility syndrome resulting from a new homozygous mutation, 888delC, in the desmosomal protein plakophilin 1

We report an unusual case of an inherited disorder of the desmosomal protein plakophilin 1, resulting in ectodermal dysplasia-skin fragility syndrome. The affected 6-year-old boy had red skin at birth and subsequently developed skin fragility, progressive plantar keratoderma, nail dystrophy, and alopecia. Skin biopsy revealed widening of intercellular spaces in the epidermis and a reduced number of small, poorly formed desmosomes. Mutation analysis of the plakophilin 1 gene PKP1 revealed a homozygous deletion of C at nucleotide 888 within exon 5. This mutation differs from the PKP1 gene pathology reported in 8 previously published individuals with this rare genodermatosis. However, all cases show similar clinical features, highlighting the importance of functional plakophilin 1 in maintaining desmosomal adhesion in skin, as well as the role of this protein in aspects of ectodermal development.

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.

Clinical and Molecular Significance of Splice Site Mutations in the Plakophilin 1 Gene in Patients with Ectodermal Dysplasia–Skin Fragility Syndrome

Clinical and Molecular Significance of Splice Site Mutations in the Plakophilin 1 Gene in Patients with Ectodermal Dysplasia–Skin Fragility Syndrome