A Case Of Autosomal Recessive Monilethrix And Literature Review

BackgroundMonilethrix is a rare hereditary alopecia disease,with moniliform appearance of hair under a light microscope.The patient's hair is sparse and easily broken and accompanied by follicular keratosis papules.There is no effective cure for this disease now.Monilethrix is an autosomal inherited disease,the autosomal dominant inheritance of monilethrix is associated with mutations in the human hair keratin genes KRT86,KRT81,and KRT83,and the autosomal recessive inheritance is associated with mutations in desmoglein 4(DSG4)gene.The basis of the pathogenesis of patients with monilethrix is due to mutations in the desmosome and keratin genes,abnormal interconnections between cells.When the tissue is exposed to external environmental stimuli such as mechanical stress,it is not enough to produce the mechanical stability required to maintain the structure and integrity of the tissue,which in turn affects the growth of the hair.Autosomal recessive monilethrix caused by mutations in the DSG4 gene is very rare and there are few domestic and foreign literature reports about its characteristics.Now we report a case of our hospital and review the literatures.ObjectiveTo report a case of an autosomal recessive monilethrix caused by DSG4 gene mutations.Literature cases were collected to discuss the general characteristics,clinical manifestations,genetic diagnosis and treatment methods of this disease,so as to provide references for the diagnosis and treatment of this disease.Methods1.Case collection1.1 Case report of our hospital:A 3-year-old female proband,her hair grew slowly for 3 years and lost hair intermittently for 1 year.Skin examination showed that the flaky hair on the top of scalp and occipital part was sparse and lost,residual broken hair and keratinized papules of hair follicles,some eyebrows and eyelashes were lost.Dermoscopy,optical microscopy and scanning electron microscopy all showed that affected hair appeared as beaded appearance.Gene sequencing test showed that the proband carried heterozygous deletionsof exons 2-16 in the DSG4 gene,and a heterozygous mutation c.574T>C(p.S192p)in the DSG4 gene,her mother carried heterozygous deletion mutation of exon 2-16 of DSG4 gene and her father carried the heterozygous mutation of DSG4 gene c.574T>c(P.S.192p).None of the 100 healthy controls of DSG4 gene showed any mutation at the above sites.According to the patient's clinical manifestations,auxiliary examination and genetic test results,the final diagnosis was autosomal recessive monilethrix caused by DSG4 gene mutation;1.2 Literatures review:To search the related databases and screen related literatures.1.2.1 Domestic literature:In terms of "monilethrix","autosomal recessive","desmoglein" and "DSG4" to search the literatures in "Chinese National Knowledge Infrastructure(CNKI)" and "Wanfang database";1.2.2 Foreign literature:In terms of "monilethrix","autosomal recessive","desmoglein" and "DSG4" to search the literatures in "PubMed";2.Inclusion criteria:(1)An autosomal recessive monilethrix caused by mutations in the DSG4 gene;(2)Gender,age,clinical manifestations,family history and genetic test results of the patients were complete;3.Exclusion criteria:(1)The publication catalogs and call for papers of magazines or journals on the website;(2)Duplicate documents;(3)The patient data were incomplete and did not meet the inclusion criteria;4.Statistical analysis:The clinical data of cases and selected literatures were collected and analyzed statistically.Results1.General informationA total of seven cases(one case in our hospital)were included,including two males and five females.The age distribution of seven patients was from seven months to 25 years old,and the median age was three years old.The onset age of all the seven cases was less than one year old,and the onset was at birth in six cases.None of the seven patients had a family history of hereditary diseases and their parents were not close relatives married.2 Clinical features2.1 Hair changeAll the seven patients had thinning hair,easy to fracture,and partial loss of eyebrows and eyelashes.2.2 Keratinized papules of hair folliclesAll the seven patients presented with keratinized papules of hair follicles,which were mainly distributed in the areas of the neck,scalp and occipital region.3.Laboratory and auxiliary examinationIn one case,the contents of trace elements iron and zinc decreased,humoral immune function decreased,and cellular immune function increased.In one case,serum IgA level decreased and serum IgE level increased.Five cases were examined by light microscope and four cases by dermoscopic examination all showed moniliform changes in the affected hair.Mycological examination of three cases were negative.Scanning electron microscopy of two cases showed obvious crimp,cracking and shedding.Transmission electron microscopy of two cases showed desmosomes reduction and abnormal keratinization.Confocal laser scanning microscopy of one case revealed moniliform changes in hair morphology,multiple hyperkeratinized papules at the hair follicle,and keratin filled in the hair follicle.4.Histopathological examination and immunohistochemical examinationHistopathology in three cases showed that there were curled endogenous hair drifts in the hair follicles,keratinized papules in the hair follicles showed mild focal hyperkeratinization,and immunohistochemical staining in two cases showed a reduction in DSG4 protein staining in affected skin.5.Genetic testingAll the seven patients underwent gene testing and analysis,and all of them found that the DSG4 gene had mutations,involving point mutations,nonsense mutations,shift mutations,translocation mutations and large-segment deletion mutations.6.TreatmentThe cases in our hospital were treated with compound glycyrrhizin tablets and erythromycin isotretinate gel,and the symptoms of hair thinning and keratinized papule were improved compared with the previous ones.In the literature,there was one case of patient who was treated with topical strong corticosteroid ointment and had no obvious effect.Conclusion1.DSG4 gene mutations are the cause of autosomal recessive monilethrix.2.This disease is clinically rare.The clinical manifestations of the patient are sparse hair and keratinized papules of the hair follicles.Affected hair with moniliform appearance can be found by light microscopy,dermoscopy and scanning electron microscopy.3.Currently,there is no standard treatment plan.Erythromycin isotretinate gel and compound glycyrrhizin tablets can partially improve the clinical symptoms of patients.