RESUMO
BACKGROUND: Desmosomes are intercellular cadherin-mediated adhesion complexes that anchor intermediate filaments to the cell membrane and are required for strong adhesion for tissues under mechanical stress. One specific component of desmosomes is plakophilin 1 (PKP1), which is mainly expressed in the spinous layer of the epidermis. Loss-of-function autosomal recessive mutations in PKP1 result in ectodermal dysplasia-skin fragility (EDSF) syndrome, the initial inherited Mendelian disorder of desmosomes first reported in 1997. METHODS: To investigate two new cases of EDSF syndrome and to perform a literature review of pathogenic PKP1 mutations from 1997 to 2019. RESULTS: Sanger sequencing of PKP1 identified two new homozygous frameshift mutations: c.409_410insAC (p.Thr137Thrfs*61) and c.1213delA (p.Arg411Glufs*22). Comprehensive analyses were performed for the 18 cases with confirmed bi-allelic PKP1 gene mutations, but not for one mosaic case or 6 additional cases that lacked gene mutation studies. All pathogenic germline mutations were loss-of-function (splice site, frameshift, nonsense) with mutations in the intron 1 consensus acceptor splice site (c.203-1>A or G>T) representing recurrent findings. Skin fragility and nail involvement were present in all affected individuals (18/18), with most cases showing palmoplantar keratoderma (16/18), alopecia/hypotrichosis (16/18) and perioral fissuring/cheilitis (12/15; not commented on in 3 cases). Further observations in some individuals included pruritus, failure to thrive with low height/weight centiles, follicular hyperkeratosis, hypohidrosis, walking difficulties, dysplastic dentition and recurrent chest infections. CONCLUSION: These data expand the molecular basis of EDSF syndrome and help define the spectrum of both the prototypic and variable manifestations of this desmosomal genodermatosis.
Assuntos
Displasia Ectodérmica/genética , Placofilinas/genética , Dermatopatias/genética , Mutação da Fase de Leitura , Mutação em Linhagem Germinativa , Homozigoto , Humanos , Hipotricose/genética , Lactente , Ceratodermia Palmar e Plantar/genética , Mutação com Perda de Função , Masculino , Unhas Malformadas/genética , LinhagemRESUMO
Background: Hereditary hypotrichosis simplex is a rare genetic hair disease that affects the scalp. Failure to grow normal hair in terms of length and density is the main complaint of patients. Diagnosis usually established by exclusion of other congenital hair and other ectodermal disorders. Till now, no satisfactory treatment was used for the condition.Report: A 14 year old patient with hypotrichosis simplex was treated with combined platelet rich plasma injection and topical minoxidil 2% with marked improvement.Conclusion: While no satisfactory treatment presents for this condition, the use of platelet rich plasma injection can add new hope for hypotrichosis simplex patients.