| Background Stiff skin syndrome(SSS)is a rare cutaneous connective tissue disorder which is highly heterogeneous.SSS is characterized by skin induration,accompanied by joint movements restricted,and mild hypertrichosis.Affected patients develop stony-hard induration of the skin at birth or under the age of 6 years,but most cases reported in the literature are not diagnosed until early or mid-childhood,which may be related to the rarity of SSS and it resemble other sclerotic diseases.Generally speaking,it does not involve the skeletal muscle and visceral system,but severe SSS patients may die.SSS has certain disability,and serious complications will cause great damage to the physical and mental health of patients and reduced quality of life.Not only has the etiology and pathogenesis of SSS not been fully elucidated,but its treatment methods are also very limited.As it is a condition with limited treatment options,prompt diagnosis and early initiation of physical therapy is crucial to prevent joint restriction and maintain quality of life.This study performed mutation screening on 1 patient with clinical diagnosis of SSS.At the same time,review the literature to discuss the clinical characteristics,histological findings,and pathogenic gene characteristics,so as to provide some experience and reference for future clinical diagnosis and treatment.Research Purposes According to the clinical manifestations of the patients and the basis of previous genetic studies,mutation screenings by whole exome sequencing to the families with SSS,and retrospective analysis of 61 cases including this patient in the world to summarize the clinical characteristics of SSS,to improve the diagnosis level of SSS,avoiding misdiagnosis and treatment,provide reference for improving the prognosis of disease.Experimental materials and methods 1.A 11-year-old boy presented with a 7-year history of indurated skin on her right lower extremity and had limited joint mobility for 6 years.Collected the patient's clinical data,and routine blood urine analysis,liver and kidney functional tests,myocardial enzymes,immunoglobulin,complement C3,complement C4,ESR,EMG,double-stranded DNA,antinuclear extract antibodies(ENA,including SCL-70,SM,SSA,SSB and other antibodies),and perfect X-rays of both lower limbs,nuclear magnetic resonance,histopathological examination,and Alcian blue staining.Collected peripheral blood samples of patients and his mothers;mutation screening by whole-exome sequencing,especially focus on screening previously reported target genes for pathogenicity.2.We retrospectively analyzed the clinical data of 60 cases of SSS have been reported,including the 1 presented in this series.Results 1.We failed to find the previously reported pathogenic gene and new pathogenic genes of SSS by whole exome sequencing,which led a negative gene diagnosis.The reason may be that part of the genetic information is omitted due to the lack of the blood sample of the patient's father in the control sample,or there may be new pathogenic genes or mutant forms of the disease and the peripheral blood whole exome sequencing method fails to find it.2.A total of 61 patients with SSS were collected in this study.The age distribution ranged from 0 to 51 years,and the average age of onset was 4.15 years.(1)In this group of data,there were 28 male patients and 33 female patients,and the ratio of male to female patients was 1: 1.178;widespread SSS were more common in clinical classification(39/61,63.79%),and there were statistics between gender and clinical classification.Significance(P<0.05).(2)The skin manifestations of the disease are mainly skin sclerosis(61/61,100%),local pigmentation(16/61,26.23%);skin sclerosis mainly affects thighs(44/55,80.00%),buttocks(35/55,63.64%)and waist(26/55,47.27%);SSS outside the skin manifestations mainly limited joint movements(41/61,67.21%),local hypertrichosis(36/61,59.02%),growth retardation(9/61,14.75%),restrictive pulmonary ventilation dysfunction(8/61,13.11%)and abnormal gait and posture(8/61,13.11%);limited joint movement often affects the knee joint(20/41,48.78%),hip joints(18/41,43.90%)and elbow joints(15/41,36.59%)and other large joints;there was no statistically significant difference between gender and the occurrence of limited joint mobility(P> 0.05),and there was no statistically significant difference in the limited joint mobility between different clinical subtypes(P>0.05);SSS combined with other diseases is relatively rare in clinical,of which esophageal hiatal hernia with gastric acid reflux is more common(3/9).(4)A total of 56 cases whose histopathological results were clearly recorded in this group of data,including mucopolysaccharide deposits in the dermis(27/56,48.21%);deep collagen dermis thickening and thickening of collagen fibers(53/56,94.64%);the absence of an inflammatory infiltrate(47/56,83.93%);adipocyte clusters visible between collagen fibers(36/56,64.29%);fibroblasts increased(17/56,30.36%);the structure of skin appendages was not abnormal(16/56,28.57%);fascial thickening(14/56,25.00%).(5)There were 23 cases of the first clinical diagnosis error,and the misdiagnosis rate was 37.70%.The first clinical diagnosis is easily misdiagnosed as scleroderma(16/23,69.57%),morphea(6/23,26.09%),connective tissue nevus(2/23,8.70%),scleredema(2/23,8.70%),eosinophilic fasciitis(1/23,4.35%)and dermatomyositis(1/23,4.35%).Conclusion 1.No pathogenic mutation was detected in a patient with SSS,which led to a negative gene diagnosis.The reason may be that some genetic information is missing due to the lack of blood samples from the father of the child in the control sample,which resulted in partial genetic information omission,or the presence of a new pathogenic gene or mutant forms of the disease.2.FBNI gene mutation is associated with the pathogenesis of widespread SSS,while segmental SSS may have new pathogenic genes or mutant forms.3.There was no significant gender difference in the incidence of SSS,but the incidence of segmental SSS was higher in females than in males.Clinical classification with widespread SSS is more common.4.The clinical manifestations of SSS are mainly localized skin stiffness,limited joint mobility,and mild hypertrichosis.Stony-hard skin occurs most commonly in the thighs,buttocks,and waist.Limited joint movements are mainly limited to large joints,such as knees,hips,and elbows.5.Adipocyte entrapment,horizontal orientation of thickened collagen bundles and no inflammatory infiltrate should be considered the histopathological hallmark of the stiff skin syndrome.6.SSS is easily misdiagnosed and needs to be distinguished from some other sclerosing diseases of the skin.Therefore,scleroderma,morphea,connective tissue nevus,scleredema and eosinophilic fasciitis are should be distinguished. |
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