Identifying a novel frameshift pathogenic variant in a Chinese family with neurofibromatosis type 1 and review of literature

AIM:To detect the pathogenic gene variant in a family with neurofibromatosis type 1(NF1).METHODS:This patient with NF1 was sequenced using target sequence capture and high-throughput sequencing technology.After detecting the suspicious pathogenic variant type,the pathogenic variant sites of the patient and the patient’s family members were verified by multiple ligation dependent probe amplification and Sanger sequencing.Sift,polyphen-2,Mutation Taster and GERP++software were used to predict the pathogenicity of the unknown loci.The clinical data,diagnosis and treatment process of the patients were reviewed.Using the keyword“NF1;frameshift pathogenic variant”,relevant literature was gathered for analysis from Chinese and international databases,with articles dating from the establishment of each database to April 2022.RESULTS:A heterozygous frameshift pathogenic variant of NF1 in exon 33 was detected in the patient.The insertion of adenine in coding region 4486 resulted in the replacement of isoleucine with asparagine in protein 1497.Sanger sequencing validation and segregation analysis were performed,which demonstrated that the NF1 gene was cosegregated with the disease phenotype in this family.This study identified a novel NF1 heterozygous frameshift mutation c.4486dupA(p.I1497Nfs*12).Relevant literature retrieval found 7 Chinese articles and 12 foreign articles.With NF1 gene mutation,mutation types are diverse,including point mutation,frameshift mutation,splice site mutation,exon mutation,chimeric mutation and de novo mutation.Foreign reports are based on autosomal dominant inheritance.CONCLUSION:This study’s results demonstrate that a novel deletion in exon 33 caused NF1 in this Chinese family,expanding the mutational spectrum of the NF1 gene.

Neurofibromatosis type 1 with multiple gastrointestinal stromal tumors:A case report

BACKGROUND Neurofibromatosis type 1(NF1)is characterized by café-au-lait patches on the skin and the presence of neurofibromas.Gastrointestinal stromal tumor(GIST)is the most common non-neurological tumor in NF1 patients.In NF1-associated GIST,KIT and PDGFRA mutations are frequently absent and imatinib is ineffective.Surgical resection is first-line treatment.CASE SUMMARY A 56-year-old woman with NF1 was hospitalized because of an incidental pelvic mass.Physical examination was notable for multiple café-au-lait patches and numerous subcutaneous soft nodular masses of the skin of the head,face,trunk,and limbs.Her abdomen was soft and nontender.No masses were palpated.Digital rectal examination was unremarkable.Abdominal computed tomography was suspicious for GIST or solitary fibrous tumor.Laparoscopy was performed,which identified eight well-demarcated masses in the jejunum.All were resected and pathologically diagnosed as GISTs.The patient was discharged on day 7 after surgery without complications.No tumor recurrence was evident at the 6-mo follow-up.CONCLUSION Laparoscopy is effective for both diagnosis and treatment of NF1-associated GIST.

Analysis of the current Covid-19 infection and vaccination status in patients with neurofibromatosis type 1

Background:To investigate the common symptoms after Covid-19 infection,characteristics of adverse events after vaccination,changes in clinical manifestations related to Neurofibromatosis type 1(NF1),as well as the current vaccination status and factors related to vaccine hesitation among NF1 patients,in order to provide a basis for scientific protection and vaccine acceptance in NF1 individuals in the new phase of pandemic management.Methods:From December 29,2022,to January 10,2023,we conducted a self-assessment questionnaire survey among diagnosed NF1 patients.General data were provided including sex,age,main clinical presentations,and current treatment.This study mainly focused on the infection and vaccination status of Covid-19 among these patients with NF1.The data were statistically analyzed using SPSS26.0 software.Results:Of the 250 questionnaires distributed,226 were valid.Among the 164 patients(72.6%)with Covid-19 infection,the most common infection symptoms and incidence of patients were not significantly different from those in the normal population(P>0.05),but the incidence of symptoms such as nasal congestion,headache,myalgia,sore throat,abdominal pain,diarrhea,and eye discomfort was higher than that in the normal population(P<0.05),and no severe infection was observed;186 patients(82.3%)had completed the Covid-19 vaccination,and more than half of those who were not vaccinated had no plans for vaccination.Among the vaccinated patients,there was no significant difference in the incidence of adverse events,such as fever,pain,redness,and swelling at the injection site after vaccination,compared to the normal population(P>0.05),but the incidence of fatigue and headache was higher in NF1 patients(P<0.001).Most patients with NF1 believe that there is no significant progressive change in NF1-related clinical manifestations after Covid-19 infection and vaccination.Conclusion:Currently,some NF1 patients appear to be worried about the evolution of their disease after Covid-19 infection in the face of large fluctuations in the pandemic situation,and some patients hesitate to receive the vaccine due to their special disease condition.Thus,clinical trials should be conducted to develop a refined pandemic response and vaccination program for this special group.

Perioperative Risk Factors for Post-operative Pneumonia after Type A Acute Aortic Dissection Surgery

Objective Type A acute aortic dissection(TAAAD)is a dangerous and complicated condition with a high death rate before hospital treatment.Patients who are fortunate to receive prompt surgical treatment still face high in-hospital mortality.A series of post-operative complications further affects the prognosis.Post-operative pneumonia(POP)also leads to great morbidity and mortality.This study aimed to identify the prevalence as well as the risk factors for POP in TAAAD patients and offer references for clinical decisions to further improve the prognosis of patients who survived the surgical procedure.Methods The study enrolled 89 TAAAD patients who underwent surgical treatment in Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei province,China from December 2020 to July 2021 and analyzed the perioperative data and outcomes of these patients.Logistic regression analyses were used to identify the risk factors for POP.Results In the study,31.5%of patients developed POP.Patients with POP had higher proportions of severe oxygenation damage,pneumothorax,reintubation,tracheotomy,renal replacement therapy,arrhythmia,gastrointestinal bleeding,and longer duration of mechanical ventilation,fever,ICU stay,and length of stay(all with P<0.05).The in-hospital mortality was 2.3%.Smoking,preoperative white blood cells,and intraoperative transfusion were the independent risk factors for POP in TAAAD.Conclusion Patients who underwent TAAAD surgery suffered poorer outcomes when they developed POP.Furthermore,patients with risk factors should be treated with caution.

Intraductal papillary bile duct adenocarcinoma and gastrointestinal stromal tumor in a case of neurofibromatosis type 1

We report our experience with a synchronous case of gastrointestinal stromal tumor(GIST) and intraductal papillary neoplasm of the bile duct(IPNB) in anelderly woman with neurofibromatosis type 1(NF-1). A 72-year-old woman presented with a 2-mo history of right upper abdominal pain unrelated to diet and indigestion. Fourteen years earlier, she had been diagnosed with NF-1, which manifested as café au lait spots and multiple nodules on the skin. Computed tomography(CT) revealed a multilocular low-density mass with septation, and mural nodules in the right hepatic lobe, as well as a 1.7-cm-sized well-demarcated enhancing mass in the third portion of the duodenum. The patient subsequently underwent right hepatectomy and duodenal wedge resection. We present here the first report of a case involving a synchronous IPNB and GIST in a patient with NF-1. Our findings demonstrate the possibility of various tumors in NF-1 patients and the importance of diagnosis at an early

A novel NF1 frame-shift mutation c.703＿704delTA in a Chinese pedigree with neurofibromatosis type 1

We analyzed the clinical features and NF1 gene mutation in a Chinese pedigree of neurofibromatosis type 1（NF1）. Three members of this family were NF1 patients presenting with different clinical phenotypes and the others were asymptomatic. Exons of NF1 were amplified by polymerase chain reaction, sequenced, compared with a reference database. One novel NF1 frame-shift mutation c.703_704delTA, which resulted in a premature stop signal at codon 720 and the synthesis of truncated, was revealed. This mutation segregated with the NF1 members is likely responsible for the pathogenesis of NF1 in the family.

Neurofibromatosis type 1-associated multiple rectal neuroendocrine tumors: A case report and review of the literature

Neurofibromatosis type 1(NF-1) is commonly associated with benign or malignant tumors in both the central and peripheral nervous systems. However, rare cases of NF-1-associated multiplerectal neuroendocrine tumors have been reported. This report describes a case of a 39 year old female with NF-1 and intermittent hematochezia as a primary symptom. Physical examination showed multiple subcutaneous nodules and café au lait spots with obvious scoliosis of the back. Imaging examinations and colonoscopy found malformation of the left external iliac vein and multiple gray-yellow nodules with varying sizes and shapes in the rectal submucosal layer. Histological and immunohistochemical results suggested multiple rectal neuroendocrine tumors, a rare disease with few appreciable symptoms and a particularly poor prognosis. The patient with NF-1 presented here had not only multiple rectal neuroendocrine neoplasms but also vascular malformations, scoliosis and other multiple system lesions. This case therefore contributes to improving clinical understanding, diagnosis and treatment of related complications for patients with NF-1 who present with associated medical conditions.

The R1947X mutation of NF1 causing autosomal dominant neurofibromatosis type 1 in a Chinese family

Neurofibromatosis type 1 is a common autosomal dominant disorder with a high rate of penetrance. It is caused by the mutation of the tumor suppressor gene NF1, which encodes neurofibromin. The main function of neurofibromin is down-regulating the biological activity of the proto-oncoprotein Ras by acting as a Ras-specific GTPase activating protein. In this study, we identified a Chinese family affected with neurofibromatosis type 1. The known gene NF1 associated with NF1 was studied by linkage analysis and by direct sequencing of the entire coding region and exon-intron boundaries of the NF1 gene. The R1947X mutation of NF1 was identified, which was co-segregated with affected individuals in the Chinese family, but not present in unaffected family members. This is the first report, which states that the R1947X mutation of NF1 may be one of reasons for neurofibromatosis type 1 in Chinese population.

Neurofibromatosis Type 1 in Four Children Cases

Neurofibromatosis Type 1 (NF-1 or Von Recklinghausen disease) is an autosomal dominant genetic disease, characterized by an extreme variability of its clinical expression which is also found in the same family. Our work focuses on the exploitation of four cases of patients with NF-1 who were enrolled in the paediatric neurology consultation at Rabat Children’s Hospital. They are two infants and two children. Otherwise the diagnosis was made in front of the existence of café au lait and lentiginous spots in two boys, also the existence of café au lait spots and abnormalities in brain imaging in two girls. Thus an evolution was marked by a favorable outcome for three patients and neurological sequelae in one patient.

Awake craniotomy for auditory brainstem implant in patients with neurofibromatosis type 2:Four case reports

BACKGROUND The auditory brainstem implant(ABI)is a significant treatment to restore hearing sensations for neurofibromatosis type 2(NF2)patients.However,there is no ideal method in assisting the placement of ABIs.In this case series,intraoperative cochlear nucleus mapping was performed in awake craniotomy to help guide the placement of the electrode array.CASE SUMMARY We applied the asleep-awake-asleep technique for awake craniotomy and hearing test via the retrosigmoid approach for acoustic neuroma resections and ABIs,using mechanical ventilation with a laryngeal mask during the asleep phases,utilizing a ropivacaine-based regional anesthesia,and sevoflurane combined with propofol/remifentanil as the sedative/analgesic agents in four NF2 patients.ABI electrode arrays were placed in the awake phase with successful intraoperative hearing tests in three patients.There was one uncooperative patient whose awake hearing test needed to be aborted.In all cases,tumor resection and ABI were performed safely.Satisfactory electrode effectiveness was achieved in awake ABI placement.CONCLUSION This case series suggests that awake craniotomy with an intraoperative hearing test for ABI placement is safe and well tolerated.Awake craniotomy is beneficial for improving the accuracy of ABI electrode placement and meanwhile reduces non-auditory side effects.

Tear inflammation related indexes after cataract surgery in elderly patients with type 2 diabetes mellitus

BACKGROUND Quantitative studies on the changes in inflammation-related content in tears,especially the effect of diabetes,are lacking.In this study,we measured the preoperative and postoperative tear inflammatory mediator levels in cataract patients,focusing on the expression of inflammatory factors in postoperative cataracts in the diabetic,and investigated the effect of drugs on the control of postoperative inflammation.AIM To study the expression of inflammatory factors in elderly people with type 2 diabetes after cataract surgery.METHODS Patients with a mean age of 70.3±6.3 years were divided into group A(composed of elderly patients with cataracts and type 2 diabetes,n=20 eyes)and group B(patients with age-related cataract,n=20 eyes).Their tears were collected before each operation and on days 1 and 3,and weeks 1,2,3,and 4 post-surgery.Saline(150μL)was dropped into the conjunctival sac of the surgical eye,followed by oculogyration in four directions.The fluid in the conjunctival sac was extracted using a sterile syringe and stored in Eppendorf tubes at-80°C until measurement.The expression levels of matrix metalloproteinase-2(MMP-2),MMP-9,tissue inhibitor of metalloproteinase-1(TIMP-1),TIMP-2,interleukin-6(IL-6),and IL-20 in tear fluid were measured using enzyme-linked immunosorbent assays.RESULTS The postoperative expression levels of MMP-2,MMP-9,TIMP-2,IL-6,and IL-20 in group A were significantly higher than those in group B,whereas the concentration of TIMP-1 in group A remained lower than that in group B.The levels of MMP-2 and IL-6 in both groups continuously increased until the peak in the first postoperative week,and then gradually decreased over the next three weeks.Ultimately,MMP-2 declined to a lower level than that preoperatively at week 4,but IL-6 decreased to the same level as that preoperatively.The level of MMP-9 peaked in the first two weeks postoperative and then returned to the same level as 1-day post-operation.The concentration of TIMP-1 post-operation remained constant at a lower level than before surgery,and TIMP-2 Levels remained stable in both groups.IL-20 content started to increase in the third week after surgery.CONCLUSION Inflammatory factor levels in tears fluctuated before and post-operation,which indicated more severe postoperative inflammation in the first two weeks.

Giant Mediastinal Neurofibroma in a Child with Neurofibromatosis Type I

Aim: There are a variety of malignant tumors related to neurofibromatosis type 1 (NF1). This report describes a rare pediatric NF1 case with an unresectable giant mediastinal tumor. Case: A 6-year-old girl with wheezing was admitted to our institution for the further evaluation of a right mediastinal mass on plain chest radiography. On examination, there were multiple café au lait spots mainly on the trunk, and a well-defined, immobile, painless mass was palpable on her neck. The mediastinal lesion was detected as nonuniform mass surrounding the aortic arch, pulmonary artery, and right main bronchus on the contrast-enhanced CT and MRI. Open biopsy was useful to rule out malignancy and revealed neurofibroma, and contributed to follow up and treatment. Discussion: Open biopsy was useful to rule out malignancy, such as malignant peripheral nerve sheath tumor, revealed neurofibroma, and also contributed to follow up and treatment. The authors report successful management by open biopsy and discuss several clinical points regarding mediastinal neurofibroma for NF1.

KIT and platelet-derived growth factor receptor α wild-type gastrointestinal stromal tumor associated with neurofibromatosis type 1: Two case reports

BACKGROUND Gastrointestinal stromal tumors(GISTs) associated with neurofibromatosis are uncommon compared to their gastrointestinal counterparts. Patients with neurofibromatosis type 1(NF-1) have an increased risk of developing gastrointestinal tumors, including rare types such as GIST.CASE SUMMARY A 60-year-old male Chinese patient was diagnosed with NF-1 10 years ago and presented with upper abdominal discomfort and black stools. Endoscopic ultrasonography and an enhanced abdominal computed tomography scan revealed a mass located 4 cm from the muscular layer of the descending duodenum. A 59-year-old Chinese woman who was diagnosed with NF-1 25 years ago presented with sudden unconsciousness and black stools. Multiple masses in the duodenum were noted by echogastroscopy and an enhanced abdominal computed tomography scan. Both patients presented with cutaneous neurofibromas. The histologic examination of tumors from both patients revealed spindle cells and low mitotic activity. Immunohistochemically, the tumor cells showed strong positivity for KIT(CD117), DOG-1, CD34, and Dehydrogenase Complex Subunit B, and negativity for SMA, desmin, S-100, and β-catenin. None of the six tumors from two patients had KIT exon 9, 11, 13, or 17 or platelet-derived growth factor receptor α exon 12 or 18 mutation, which is a typical finding for sporadic GISTs. None of the six tumors from the two patients had a BRAFV600 E mutation. The patients were alive and well during the follow-up period(range:0.6-5 yr).CONCLUSION There have been only a few previous reports of GISTs associated with NF-1.Although GISTs associated with NF-1 have morphologic and immunohistochemical similarities with GISTs, the pathogenesis, incidence,genetic background, and prognosis are not completely known. A medical history of NF-1 in a patient who has gastrointestinal bleeding or anemia and an intraabdominal mass with nonspecific computed tomography features may help in diagnosing GIST by virtue of the well-known association of these two entities.Molecular genetic studies of cases indicated that GISTs in NF-1 patients have a different pathogenesis than sporadic GISTs.

Neurofibromatosis type 2 gene mutation and progesterone receptor messenger RNA expression in the pathogenesis of sporadic orbitocranial meningioma

AIM: To investigate neurofibromatosis type 2(NF2) gene mutation at mRNA levels in sporadic orbitocranial meningioma and its association with progesterone receptor(PR) mR NA expression.METHODS: This was a case-control study. Thirty-four sporadic meningioma patients with no familial NF2-related meningioma history were recruited. They were interviewed for their obstetric, gynecologic, and contraception history. PR investigation was performed with real-time polymerase chain reaction(PCR). NF2 mutation was investigated using Qbiomarker Somatic Mutation PCR Assay at NF2 mRNA level after its cDNA extraction(four mRNA mutation cytoband coordinates for nucleotide change: c.634 C>T/p.Q212, c.655 G>A/p.V219 M, c.784 C>T/p.R262 and c.1228 C>T/p. Q410). RESULTS: After mutation analysis at mRNA level, NF2 gene mutation was found in 35.29% patients. Non-mutation group was strongly associated with exogenous hormonal exposure(non-mutation vs mutation: 95.5% vs 83.3%, P<0.001). PR mR NA was found significantly lower in nonmutation group(P=0.033) which presumed as long term exogenous progesterone exposure. However, mutation group was associated with higher rate of progression to gradeⅡ(mutation vs non-mutation, 18.2% vs 5%, P<0.001) and was associated more in fibrous and anaplastic tumor tissue.CONCLUSION: NF2 mutation-meningioma is associated with higher grade of meningioma. Non NF2 mutationmeningioma is strongly associated with exogenous progesterone exposure and lower PR expression.

Type Ⅰ neurofibromatosis with spindle cell sarcoma: A case report

BACKGROUND Neurofibromatosis type Ⅰ(NF1) is the most frequent subtype of neurofibromatosis. Its related tumor-suppressor syndromes are characterized by a predisposition to multiple tumor types and other disorder presentations. In addition, the incidence of tumors is much higher in patients with neurofibromatosis type Ⅰ. However, there are very few reports at home and abroad on this topic. Here, we present a case of NF1 with spindle cell sarcoma.CASE SUMMARY A 50-year-old male was found to have a right axillary mass for 20 years.Specialist examination found cafe-au-lait spots on many parts of the skin,rounded nodules in the skin, a bulge in the right armpit, touching a lump(10 cm× 6 cm, hard, unclear boundary, poor mobility, local tenderness). The anterior side of the thigh felt weakened on the opposite side;in the right groin a swollen lymph node(hard, clear border, good mobility, local tenderness). According to the results of positron emission tomography/computed tomography, puncture pathology and immunohistochemistry, genetic testing, a diagnosis of NF1 with spindle cell sarcoma was confirmed. According to the genetic testing result, the patient was given a targeted treatment with crizotinib.CONCLUSION Surgery, chemotherapy and radiotherapy are the main treatment methods of NF1. However, with the continuous progress of molecular biology research,molecular targeted therapy may bring benefits for patients.

Analysis of long-term outcome of modified gastric bypass for type 2 diabetes mellitus in Chinese patients

BACKGROUND Bariatric and metabolic surgery have been routinely performed following the rapid increase in obesity and metabolic diseases worldwide.Of all evolving procedures,Roux-en-Y gastric bypass(RYGB)is considered the gold standard for surgical treatment of patients with type 2 diabetes mellitus(T2DM)and obesity.RYGB was introduced in China nearly 20 years ago,but the number of RYGB surgeries only accounts for 3.1%of the total number of weight loss and metabolic surgeries in China,it’s effect on Chinese people still needs further study.AIM To investigate the effect and safety of a modified gastric bypass performed in Chinese patients with T2DM.METHODS Patients with obesity and T2DM who underwent modified gastric bypass,with>5-year follow-up data,were analyzed.RESULTS All 37 patients underwent uneventful laparoscopic surgery,no patient was switched to laparotomy during the surgery,and no severe complications were reported.Average weight and body mass index of the patients reduced from 84.6±17.3(60.0–140.0)kg and 30.9±5.0(24.7–46.2)kg/m2 to 67.1±12.2(24.7–46.2)kg and 24.6±3.9(17.7–36.5)kg/m2,respectively,and fasting plasma glucose and glycated hemoglobin decreased from 7.4±3.4 mmol/L and 8.2%±1.7%preoperatively to 6.5±1.3 mmol/L and 6.5%±0.9%5-years postoperatively,respectively.Only 29.7%(11/37)of the patients used hypoglycemic drugs 5-years postoperatively,and the complete remission rate of T2DM was 29.7%(11/37).Triglyceride level reduced significantly but high-density lipoprotein increased significantly(both P<0.05)compared with those during the preoperative period.Liver and renal function improved significantly postoperatively,and binary logistic regression analysis revealed that the patients’preoperative history of T2DM and fasting C-peptide were significant prognostic factors influencing complete T2DM remission after RYGB(P=0.006 and 0.012,respectively).CONCLUSION The modified gastric bypass is a safe and feasible procedure for Chinese patients with obesity and T2DM,exhibiting satisfactory amelioration of weight problems,hyperglycemia,and combination disease.

Conversion surgery after gemcitabine and cisplatin plus durvalumab for advanced intrahepatic cholangiocarcinoma:A case report

BACKGROUND The combination of immune checkpoint inhibitors and chemotherapy has shown promising results for the treatment of advanced biliary tract cancer(BTC).Based on the results of the TOPAZ-1 trial,a gemcitabine and cisplatin plus durvalumab(GCD)regimen was recently approved as first-line therapy for patients with advanced BTC.However,post-GCD conversion surgery has not been previously studied.Herein,we describe a case of advanced intrahepatic cholangiocarcinoma(ICC)successfully treated with radical surgery after GCD.CASE SUMMARY A 65-year-old female diagnosed with advanced ICC with periductal infiltration into the hepatic hilum underwent eight cycles of GCD,followed by durvalumab maintenance treatment,with mild adverse events.Partial response was obtained.Subsequently,a conversion surgery with extended left hepatectomy and bile duct resection was performed.The resection margins were negative,and the pathological diagnosis was compatible with small duct type ICC.The patient remained disease-free for 8 months without adjuvant chemotherapy.CONCLUSION We describe the case of a patient who received successful conversion surgery after GCD treatment for advanced ICC.

Remission of type 2 diabetes mellitus

The surge in type 2 diabetes mellitus(T2DM)is tightly linked to obesity,leading to ectopic fat accumulation in internal organs.Weight management has become a cornerstone of T2DM treatment,with evidence suggesting that significant weight loss can induce remission.Remission,defined as sustained hemoglobin(HbA1c)below 6.5% for at least 3 months without medication,can be achieved through various approaches,including lifestyle,medical,and surgical interventions.Metabolic bariatric surgery offers significant remission rates,particularly for patients with severe obesity.Intensive lifestyle modifications,including lowcalorie diets and exercise,have also demonstrated significant potential.Medications like incretin-based agents show robust results in improving beta-cell function,achieving glycemic control,and promoting weight loss.While complete remission without medication may not be attainable for everyone,especially those with severe insulin resistance or deficiency,early and aggressive glycemic control remains a crucial strategy.Maintaining HbA1c below 6.5%from the time of diagnosis reduces the risk of long-term complications and mortality.Moreover,considering a broader definition of remission,encompassing individuals with sustained control on medication,could offer a more comprehensive and inclusive approach to managing this chronic disease.

Neurofibromatosis type Ⅰ caused by a splicing mutation in NF1 using targeted next generation sequencing

Objective Neurofibromatosis typeⅠ(NF1)is an autosomal dominant disorder which is caused by loss-of-function mutations in neurofibromin 1 gene(NF1).Clinically,NF1 mainly manifests several typical features,such as multiple neurofibromas and café-au-lait spots,as well as axillary freckling and Lisch nodules in iris.The aim of the current study is to identification a splicing mutation and genotype-phenotype correlation.

Vascular anomaly in the levator aponeurosis of neurofibromatosis type 1

Dear Editor,I am Satoru Kase,from the Department of Ophthalmology,Faculty of Medicine and Graduate School of Medicine,Hokkaido University,Sapporo City,Japan.I write to present a case of neurofibromatosis type 1（NF1）showing massive hemorrhage during involutional blepharoptosis surgery.