日本発のHHT関連の2011年以降の最近の論文をlist upします.

Ozawa H, Ohki T, Kanaoka Y, Maeda K, Hagiwara S: Open arterial reconstruction of multiple hepatic artery aneurysms in a patient with hereditary hemorrhagic telangiectasia: A case report. Medicine (Baltimore) 95:e5430, 2016


Hereditary hemorrhagic telangiectasia (HHT) is characterized by mucocutaneous telangiectasia and visceral vascular malformations (VMs). Liver involvement with VMs may lead to high-output cardiac failure, portal hypertension, and biliary disease. There is no curative treatment for the disease, and liver transplantation is indicated for life-threatening complications. Herein, we report a case of multiple hepatic artery aneurysms (HAAs) in a patient with HHT in which open arterial reconstruction was performed. There have only been a few case reports on HAA occurring with HHT. Thus, this case provides important information for the management of HHT-associated HAAs.


A 62-year-old female with known HHT was referred to our facility to seek further treatment for a giant HAA. She denied any symptoms except recurrent epistaxis. A computed tomography (CT) scan revealed a right HAA with a diameter of 72 mm, in addition to 2 other minor HAAs. The CT scan also revealed the VMs that were scattered in the liver, and a continuously dilated and tortuous artery existing from the celiac trunk to the right and left hepatic arteries. We performed open arterial reconstruction of the HAAs. Her postoperative course was uneventful.


When treating HAAs, there are a variety of options. However, hepatic VMs might affect HHT patients in various ways postprocedurally. Ligation and embolization of the hepatic artery may lead to complications, such as massive hepatic necrosis. Hepatectomy should be avoided if possible, because a postoperative hyperperfusive state in the remaining liver can cause adverse events. We believe that arterial reconstruction of HHT-associated HAAs might reduce the risk of postprocedural complications with minimal hemodynamic changes in the liver, thus obviating the need for hepatectomy or liver transplantation.

Miyake R, Fujino T, Abe K, Hosokawa K, Ohtani K, Morisaki H, Yamada O, Higo T, Ide T:  Pulmonary arterial hypertension associated with hereditary hemorrhagic telangiectasia successfully treated with sildenafil. Int J Cardiol 214:275-276, 2016 (no abstract available)

Yoshioka Y, Nozawa H, Tanaka J, Nishikawa T, Tanaka T, Kiyomatsu T, Kawai K, Hata K, Kazama S, Yamaguchi H, Ishihara S, Sunami E, Kitayama J, Watanabe T: Small bowel adenocarcinoma arising in a patient with hereditary hemorrhagic telangiectasia: A case report. Oncol Lett 11:2137-2139, 2016

Patients with hereditary hemorrhagic telangiectasia (HHT) are reportedly at a lower overall risk of malignancies, and small bowel adenocarcinoma (SBA) arising in a HHT patient is extremely rare. In this study, the case of a 37-year-old female with HHT who developed a poorly differentiated jejunal adenocarcinoma five years after ileocecal resection for multiple colonic adenomas is presented. The patient underwent curative resection of the cancer invading the ileum and the mesentery of the transverse colon, but had to overcome critical complications perioperatively, stemming from HHT-associated peripheral capillary dilatation and arteriovenous malformation, including nosebleeds and possible infusion-induced air embolism through pulmonary shunts. The patient subsequently received adjuvant chemotherapy including capecitabine and oxaliplatin for 6 months, and currently remains alive without any evidence of recurrence 12 months after the second surgery. This patient with SBA was an instructive case demonstrating the necessity of careful attention during major surgery in HHT.

Minami K, Haji T: Intranasal topical estrogen in the management of epistaxis in hereditary hemorrhagic telangiectasia. Acta Otolaryngol 2016 Jan 25:1-4 (Epub ahead of print)

Conclusion Application of topical estriol ointment is an effective treatment for hereditary hemorrhagic telangiectasia (HHT) epistaxis. Objective HHT is an autosomal-dominant disease characterized by epistaxis in more than 96% of patients. Management of this major symptom, epistaxis, has not been standardized. This study reports experience with topical application of estriol in patients with HHT. Methods Five patients with a confirmed diagnosis of HHT who first visited the hospital between 2012 and 2013 received 0.1% estriol ointment and were guided to apply the ointment twice daily to the anterior part of both nasal cavities. Severity of epistaxis was valued using epistaxis severity score (ESS) before and 3 months after initiating therapy. Results Five patients (three males, two females) received treatment. After the initiation of treatment, intensity and frequency of epistaxis became moderate in all patients. ESS decreased significantly from pre- to post-treatment (p = 0.043). No adverse events were recorded during follow-up.

Ichimura K, Kikuchi H, Imayoshi D, Dias MS: Topical application of timolol decreases the severity and frequency of epistaxis in patients who have previously undergone nasal dermoplasty for hereditary hemorrhagic telangiectasia. Auris Nasus Larynx 2015 Dec 28, pii: S0385-8146(15)30001-8. doi: 10.1016/j.anl.2015.12.001. [Epub ahead of print]

OBJECTIVE:Hereditary hemorrhagic telangiectasia (HHT) is widely known to cause bleeding that is difficult to control because of the associated vascular wall fragility. Although nasal dermoplasty results in decreased severity and frequency of nasal bleeding in patients with HHT, it does not eradicate epistaxis because this procedure cannot cover the entire nasal cavity. Residual bleeding warrants additional effective therapy. Preliminary reports on the use of β-adrenergic blockers for treating epistaxis in patients with HHT encouraged us to examine their effects in HHT patients who had previously undergone nasal dermoplasty but still complained of epistaxis.

METHODS:We performed a prospective topical timolol, a nonselective beta blocker, application study involving 12 HHT patients who had undergone nasal dermoplasty. The observation period lasted for 3 months.

RESULTS:There was one improperly enrolled case in which timolol administration was discontinued. The mean score of bleeding intensity and that of bleeding frequency were markedly reduced after treatment. Two patients who had required transfusions before treatment did not need them afterward, and patients were generally satisfied with the treatment.

CONCLUSION:Topical timolol application was effective in decreasing epistaxis. Although no adverse effects were observed in the properly selected patients, there are contraindications to timolol application that should be kept in mind when applying this treatment.

Shimoda Y, Osanai T, Nakayama N, et al: De novo arteriovenous malformation in a patient with hereditary hemorrhagic telangiectasia. J Neurosurg Pediatr (in press)

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant systemic disorder characterized by the enlargement of capillaries, recurrent nosebleeds, and multiple arteriovenous malformations (AVMs). Although cerebral AVMs are traditionally considered to be congenital lesions, some reports have described de novo AVMs, which suggests that the authors believed them to be dynamic conditions. In this article, the authors describe the case of a 5-year-old boy with HHT in whom a de novo cerebral AVM was detected after a negative MRI result at 5 months. To the authors' knowledge, this is the first report of a de novo AVM in a patient with HHT. In patients with a family history of HHT, de novo AVMs are possible, even when no lesions are detected at the first screening. Therefore, regular screenings need to be performed, and the family should be informed that AVMs could still develop despite normal MRI results.

Nishioka Y, Akamatsu N, Sugawara Y, et al: Hereditary hemorrhagic telangiectasia with hepatic vascular malformations. Cade Rep Med 2015; 2015:917818. doi: 10.1155/2015/917818. Epub 2015 May 21.

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant hereditary disease. Early diagnosis is important to avoid complications from vascular lesions, but diagnosis is difficult in asymptomatic patients. A 69-year-old Japanese male patient was referred to our hospital for evaluation of hepatic vascular malformations. He had mild anemia with iron deficiency, and dynamic contrast-enhanced computed tomography revealed significant arteriovenous and arterioportal shunts throughout the liver. Telangiectasia from the pharynx to the duodenum was confirmed by gastrointestinal endoscopy. The patient history revealed episodes of epistaxis as well as a family history of epistaxis. He was diagnosed with HHT, although no other family member had been diagnosed with definite HHT. A diagnosis of HHT must be considered in patients with hepatic vascular malformations.

Komiyama M, et al: Neuroradiological manifestations of hereditary hemorrhagic telangiectasia in 139 Japanese patients. Neurol Med Chir (Tokyo) 55:479-486, 2015, doi:10.2176/nmc.oa.2015-0040

The purpose of this study is to report the neuroradiological manifestations of hereditary hemorrhagic telangiectasia (HHT). One hundred and thirty-nine Japanese HHT patients (73 men and 66 women, aged 2–78 years) were included in this study. Diagnosis of HHT was based on genetic analysis and/or clinical diagnosis of Curaçao. They included 68 HHT1 and 37 HHT2 patients. Essentially, all patients underwent brain magnetic resonance imaging (MRI) and pulmonary computed tomography (CT). Contrast enhanced studies of brain MRI and hepatic CT were performed in a subset of patients. Catheter cerebral angiography was performed when indicated. Their neuroradiological features were reviewed retrospectively. Various imaging abnormalities were found. Brain arteriovenous malformations (AVMs) were observed in 27/136 patients (19.9%, 21 patients with HHT1 and 1 patient with HHT2). Pulmonary arteriovenous fistulas (AVFs) were found in 73/137 patients (65.2%, 45 patients with HHT1 and 6 patients with HHT2). Cerebral infarction and brain abscess were found in 17 patients and 3 patients with pulmonary AVFs, respectively. T1 high lesions in the basal ganglia suggestive of porto-venous shunts were observed in 51/136 patients (37.5%, 9 patients with HHT1 and 28 patients with HHT2). Hepatic AVMs were observed in 61/136 patients (44.9%, 15 patients in HHT1 and 29 patients in HHT2). Brain AVMs and pulmonary AVFs were more common in HHT1 than in HHT2 (both p < 0.01), but hepatic AVMs were conversely more common in HHT2 than in HHT1 (p < 0.01). In conclusion, HHT patients present with a variety of neuroradiological manifestations, which are related to substantial causes of morbid-mortality in HHT.

小宮山雅樹:遺伝性出血性毛細血管拡張症.脳卒中の外科 43:193-200, 2015

Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Rendu-Weber disease, is not a rare, but under-recognized autosomal dominant disorder that results from multi-system vascular dysplasia. It is characterized by mucocutaneous telangiectases and arteriovenous malformations (AVMs) of the brain, lung, liver and spinal cord. Neurological manifestation is either due to paradoxical embolism from the pulmonary AVM or hemorrhage of AVMs of the brain and spinal cord. This article summarizes the clinical features of HHT and its managements, and also emphasizes the high index of suspicion of this disease in patients with characteristic clinical manifestations.

Saji N, Kawarai T, Miyamoto R, et al: Exome sequencing identifies a novel intronic mutation in ENG that causes recurrence of pulmonary arteriovenous malformations. J Neurol Sci 352:29-33, 2015 doi: 10.1016/j.jns.2015.02.007. Epub 2015 Apr 2.

Hereditary hemorrhagic telangiectasia (HHT) occasionally can be discovered in patients with cerebrovascular disease. Pulmonary arteriovenous malformation (PAVM) is one of the complications in HHT and occasionally is causative for life-threatening embolic stroke. Several genetic defects have been reported in patients with HHT. The broad spectrum of phenotype and intrafamilial phenotype variations, including age-at-onset of vascular events, often make an early diagnosis difficult. We present here a Japanese family with a novel intronic heterozygous mutation of ENG, which was identified using whole exome sequencing (WES). The intronic mutation, IVS3+4delAGTG, results in in-frame deletion of exon 3 and would produce a shorter ENG protein lacking the extracellular forty-seven amino acid sequences, which is located within the orphan domain. Our findings highlight the importance of the domain for the downstream signaling pathway of transforming growth factor-beta and bone morphogenesis protein superfamily receptors. Considering the phenotype variations and the available treatment for vascular complications, an early diagnosis using genetic testing, including WES, should be considered for individuals at risk of HHT.

Komaki Y, Kanmura S, Funakawa K, Komaki F, Hashimoto S, Taguchi H, Numata M, Fujita H, Uto H, Ido A, Tsubouchi H: A case of hereditary hemorrhagic telangiectasia with repeated hemobilia arrested by argon plasma coagulation under direct peroral cholangioscopy. Gastrointest Endosc 80:528-9, 2014

小宮山雅樹:遺伝性出血性毛細血管拡張症.循環器内科 77:327-330, 2015

Kato Y, Maruyama H, Uchino A, Tanahashi N: Late-onset portosystemic encephalopathy in a patient with Rendu-Osler-Weber disease. Intern Med 53:2653-2654, 2014 (no abstract available)

Nakamura Y, Shinkata F, Ryugo M, et al: Redo cardiac surgery for active prosthetic valve endocarditis associated with hereditary hemorrhagic telangiectasia: report of a case. Surg Today 44:2378-2381, 2014

Hereditary hemorrhagic telangiectasia (HHT) is caused by an autosomal dominant gene and characterized by multiple arteriovenous malformations in several organs, leading to bleeding or shunting. These patients often suffer severe infections and heart failure, which should be managed in the perioperative period, when open heart surgery is indicated. We report a case of successful aortic root replacement for active prosthetic valve endocarditis and ventricular septal perforation in a patient with HHT, who had severe heart failure.

Ishiwata T, Terada J, Tanabe N, et al: Pulmonary arterial hypertension as the first manifestation in a patient with hereditary hemorrhagic telangiectasia. Intern Med 53:2359-2363, 2014

A 17-year-old Japanese girl visited our hospital for an evaluation of exertional dyspnea. A diagnosis of pulmonary arterial hypertension (PAH) was confirmed based on the findings of right heart catheterization. Detailed questioning revealed a family history of hereditary hemorrhagic telangiectasia (HHT), and a genetic mutation analysis disclosed a mutation in the activin receptor-like kinase 1 gene (ACVRL1). The patient was finally diagnosed with HHT according to the Curaçao diagnostic criteria eight years after the diagnosis of PAH. This case supports previous reports indicating that signs of PAH can be the first manifestation of disease in ACVRL1 mutation carriers.

山本慶子、須田 明、飯田智彦、他:胸腔内出血をきたした妊娠合併遺伝性出血性毛細血管拡張症の1例.日本呼吸器学会誌 2:782-787, 2013

症例は35歳、女性.21歳時に肺動静脈瘻(pulmonary arteriovenous fistula: pAVF)の診断で肺部分切除術を施行されている.27歳時、遺伝性出血性毛細血管拡張症(hereditary hemorrhagic telangiectasia: HHT)の診断を受けるも、医療機関による経過観察は受けていなかった.今回、第3子妊娠25週0日に胸痛を主訴に受診し、pAVFの破裂による胸腔内出血と診断され緊急入院となった.保存的に止血は得られたが、再出血の危険性が高いと判断され妊娠26週4日に肺部分切除術を施行.妊娠36週6日に帝王切開にて正常女児を出産した.HHT合併妊婦でpAVF破裂をきたしながらも母体・児ともに無事出産しえた貴重な症例である.

   Fukushima H, Mitsuhashi T, Oto T, et al: Successful lung transplantation in a case with diffuse pulmonary arteriovenous malformations and hereditary hemorrhagic telangiectasia. Am J Transplant 13:3278-3281, 2013. doi: 10.1111/ajt.12499. Epub 2013 Oct 24.

Diffuse pulmonary arteriovenous malformations (AVMs) are associated with a poor prognosis and the therapeutic strategy remains controversial. We describe a pediatric patient with diffuse pulmonary AVMs associated with hereditary hemorrhagic telangiectasia (HHT), who presented with two cerebral AVMs in the parietal and occipital lobes as well. Of note, successful bilateral lung transplantation not only improved the hypoxemia but also resulted in size reduction of the cerebral AVMs. Although it is essential to consider involvements other than pulmonary AVMs, especially brain AVMs, to decide the indication, lung transplantation can be a viable therapeutic option for patients with diffuse pulmonary AVMs and HHT.

 Komiyama M, Ishiguro T, Yamada O, et al: Hereditary Hemorrhagic Telangiectasia in Japanese Patients. J Hum Genet, doi:10.1038/jhg.2013.113, 7 November 2013

Objective: To describe clinical presentations of hereditary hemorrhagic telangiectasia (HHT) patients in Japan.

Materials: There were 80 patients (40 men and 40 women, age 2-78, mean 39.4 years old), who were either genetically verified or genetically not-identifiable but clinically definite HHT patients. Clinical presentations of these HHT patients were analised retrospectively. Radiological examinations, which included at least brain MR imaging and lung CT, were performed when indicated.

Results: Seventy-eight patients had either endoglin or activin A receptor type II-like 1 (ACVRL1) mutation. They were 53 HHT1 patients with endoglin mutation in 27 families and 25 HHT2 patients with ACVRL1 mutation in 17 families. Two other female patients were clinically definite HHT, but genetic mutation could not be identified. Nosebleeds were noted in 53/53 (100%) HHT1 and 24/25 (96%) HHT2 patients. Telangiectases were observed in 34/53 (64%) HHT1 and 18/25 (72%) HHT2 patients. Pulmonary arteriovenous malformations (AVMs) were noted in 33/52 HHT1 (63%) and 5/25 HHT2 patients (20%). Brain AVMs were detected in 12/51 HHT1 (24%) and 1/25 HHT2 (4%) patients. Hepatic AVMs were noted in 7/29 (24%) HHT1 and 16/20 (80%) HHT2 patients.

Conclusions: The number of HHT1 patients was roughly twice as many as that of HHT2 patients in Japan. Pulmonary and brain AVMs were predominantly observed in HHT1 while hepatic AVMs were detected in HHT2. It seemed that ethnicity and regionality played minimal roles in the clinical presentation of HHT.

  Komiyama M, Ishiguro T, Umaba, et al: Transcardiac, retrograde transvenous embolization of proximally occluded pulmonary arteriovenous malformation. CardioVasc Interv Radiol DOI 10.1007/s00270-013-0755-3, 23 October 2013

Purpose: to report a novel transcardiac, retrograde transvenous coil embolization of inadequately proximally occluded pulmonary arteriovenous malformation (AVM).

Case presentation: Pulmonary AVM in the right A4 segment in an 8-year-old boy with hereditary hemorrhagic telangiectasia was initially treated by proximal occlusion of the feeding artery with coils. Six years later, recurrent AVM caused dyspnea on exertion. The A4 AVM was re-perfused by many collaterals from local pulmonary arteries. By Brockenbrough procedure, an 8F long sheath was introduced from right atrium to left atrium. A 7F balloon catheter was then coaxially introduced into right middle pulmonary vein. Then, a microcatheter was introduced retrogradely from pulmonary vein to pulmonary artery through the recurrent AVM. The venous sac as well as the distal arterial segment of the A4 AVM was successfully embolized with detachable coils. The A4 AVM was completely occluded. No adverse effects were observed and dyspnea on exertion disappeared.

Conclusion: This novel transcardiac, retrograde transvenous embolization is useful for inadequately treated pulmonary AVM with proximal feeding artery occlusion.

 住友靖彦、山下幸政、板井良輔、他:SMAD4の変異が証明された若年性ポリポーシス/遺伝性出血性末梢血管拡張症複合症候群の1例.日消誌 110:64-73, 2013

症例は47 歳男性.胸部異常陰影を指摘され受診し,胸部MRI などにて肺動静脈奇形と判明した.また反復する鼻出血や皮膚の毛細血管拡張を認めたことから,遺伝性出血性末梢血管拡張症と診断した.大腸に多数の若年性ポリープを認め,49 歳時にSMAD4 遺伝子の生殖細胞系変異が検出され,若年性ポリポーシス遺伝性出血性末梢血管拡張症複合症候群と診断された.本症例はSMAD4 変異をともなう本症の本邦最初の報告例である.

   Morita H, Kimura N,  Yuri K, et al: Bentall Operation for Prosthetic Valve Endocarditis with Hereditary Hemorrhagic Telangiectasia. Thorac Cardiovasc Surg   http://dx.doi.org/10.5761/atcs.cr.12.01933

Hereditary hemorrhagic telangiectasia (HHT; Osler–Weber–Rendu syndrome) is an uncommon disease characterized by abnormal telangiectasias and arteriovenous malformations that cause recurrent bleeding. Here, we present the case of a patient with HHT, who had a history of pulmonary and hepatic arteriovenous malformations and endocarditis of a prosthetic aortic valve that was caused by methicillin-resistant Staphylococcus aureus. The patient underwent the Bentall operation after coil embolization for pulmonary arteriovenous malformations. The postoperative course was uneventful.

   NIshida T, Faughnan ME, Krings T, et al: Brain arteriovenous malformations associated with hereditary hemorrhagic telangiectasia: gene-phenotype correlations. Am J Med Genet A, 156A:2829-2834, 2012, DOI 10.1002/ajmg.a.35622

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disease with a wide spectrum of vascular malformations (VMs) involving multiple organs. Nine to 16% of patients withHHTharbor brain arteriovenous malformations (AVMs), which can cause intracranial hemorrhage (ICH). Our objective was to study clinical manifestations of brain AVMs in patients with HHT and correlate these with the specific gene mutated. We reviewed records of 171 patients with HHT and brain AVMs. A history of ICH was found in 27% (41/152) patients, with a mean age of 2618 range, (0–68) years. All of patients with ICH were neurologically asymptomatic prior to ICH. Multiple brain AVMs were found in 23% (170/39) of patients on initial examination. Genetic test results were available in 109 (64%) patients. Mutations in ENG, ACVRL1, and SMAD4 were present in 75 (69%), 18 (17%), and 2 (2%), respectively. A history of ICH was reported in 24% of patients with an ENG mutation and 27% of patients with an ACVRL1 mutation, with a mean age of 2616 (range, 2–50) and 1821 (0–48) years, respectively. No statistically significant differences in age at first brain AVM diagnosis, prevalence of ICH history, age atICH, or othermanifestations of brainAVMswere observed among gene groups. In conclusion, no evidence for differences in brain AVM characteristics was observed among HHT gene groups, although we cannot exclude clinically important differences. Larger studies are needed to further guide brain AVM screening decisions in patients with HHT.

 瀬川正孝: 肺動静脈瘻を切除したRendu-Osler-Weber病. 胸部外科 65:862-865, 2012

A 36-year-old man was admitted to our hospital for examination of a nodular shadow in the left lung. Chest 3-dimensional computed tomography (3D-CT) revealed a pulmonary arteriovenous fistula (PAVF) of 21 mm in diameter composed of the feeding artery (A4) and the draining vein (V4) in the left S4. Abdominal enhanced CT revealed multiple hepatic arteriovenous fistula. Brain CT revealed a cavernous hemangioma in right occipital cerebrum. He had a family history, habitual epistaxis, and oral  telangiectasia and was diagnosed as Rendu-Osler-Weber disease (hereditary hemorrhagic telangiectasia:HHT). According to his family history, PAVF was likely to be a risk factor of brain infarction and abscess, and the wedge resection of the lingual lobe was performed to remove PAVF.

 Sugiyama T, Nakayama N, Terasaka S, et al: Giant calcified thrombosed varices secondary to a pial arteriovenous fistula associated with hereditary hemorrhagic telangiectasia. Neurol Med Chir (Tokyo) 52:506-509, 2012

A 28-year-old woman presented with an unusual case of giant thrombosed varix with calcified walls that had mass effects secondary to a pial single-channel arteriovenous fistula (AVF) associated with  hereditary hemorrhagic telangiectasia (HHT). She consulted our hospital for chronic headache. She had been diagnosed with HHT based on genetic testing when her 3-year-old son presented with subarachnoid hemorrhage due to spinal AVF. Imaging studies revealed pial single-channel AVF with multiple varices. The varices in the right frontal lobe were over 6 cm in diameter and had laminar thromboses and calcified walls. Because of the mass effect, direct surgical flow disconnection was performed followed by removal of the varices using an internal decompression technique. Postoperatively, the patient was discharged with no neurological symptoms and no longer suffered chronic headache. Intracerebral varices are occasionally associated with high-flow AVF, and usually treated by interrupting the feeding arteries  leaving the varices intact. This extremely rare case of intracerebral giant thrombosed varices with  calcified wall and mass effect indicates that surgical removal of varices should be considered.

 Ishii D, Takechi A, Seyama G, et al: Ruptured large basilar artery aneurysm associated with an arteriovenous malformation in hereditary hemorrhagic telangiectasia. Neurol Med Chir (Tokyo) 52:502- 505, 2012

A 53-year-old woman presented with intracranial hemorrhage caused by a ruptured cerebral aneurysm. Digital subtraction angiography revealed a large aneurysm arising from the top of the basilar artery and a Spetzler-Martin grade 3 arteriovenous malformation. Endovascular embolization of the aneurysm was completed with a slight neck remnant. Medical examination confirmed that she suffered from hereditary hemorrhagic telangiectasia (HHT). HHT is a rare autosomal dominant disorder characterized by multiple mucocutaneous telangiectasia and associated vascular malformations. This case suggests that the prognosis for HHT patients with treatable aneurysms should be as good as that of healthy individuals. Consequently, neurosurgeons should suspect underlying HHT in all patients with cerebral vascular malformations.

 Suzuki A, Nakashima D, Miyawaki Y, et al: A novel ENG mutation causing impaired co-translational processing of endoglin associated with hereditary hemorrhagic telangiectasia. Thromb Res 129:e200-208, doi: 10.1016/j.thromres.2011.12.030. Epub 2012 Mar 3.

Hereditary hemorrhagic telangiectasia (HHT) is an inherited autosomal dominant vascular dysplasia caused by mutations in mainly the endoglin gene (ENG) or activin-like kinase receptor 1 (ALK1) gene (ACVRL1). We investigated the molecular basis of HHT in a Japanese patient, and identified a novel missense mutation in ENG (c.38T>A, p.Leu13Gln) located in the signal peptide's hydrophobic core, but not in ACVRL1. In experiments in COS-1 cells, the Leu13Gln (L13Q) mutant endoglin appeared to be expressed as a precursor form, probably due to impaired protein processing. Flow cytometry analyses of the COS-1 cells transiently expressing recombinant endoglins revealed that the wild-type endoglin was detected on the cell surface, but the L13Q mutant was not. We also analyzed expression patterns of the recombinant endoglins by immunofluorescent staining, and found that the wild-type co-localized with the endoplasmic reticulum (ER), but the L13Q mutant did not. These results implied that the L13Q mutant endoglin fails to insert into the ER, probably due to destruction of the hydrophobic core structure in the signal peptide to be recognized by signal recognition particles. Thus, the Leu13 in the signal peptide of endoglin might be essential for correct protein processing through the ER and cell-surface expression. Taken together, the novel c.38T>A mutation in ENG would impair co-translational processing of the endoglin, and could be responsible for HHT in this patient.

 Ichimura K, Kikuchi H, Imayoshi S: A new method of nasal dermoplasty (MW grafting method) in patients with large septal perforation. Laryngoscope. 121:1715-1717, 2011

Nasal dermoplasty is effective in controlling epistaxis in patients with hereditary hemorrhagic telangiectasia (HHT). Skin graft take failure occurs mostly in cases of large septal perforation. The MW method was developed as a modification of nasal dermoplasty designed for patients with HHT having a large septal perforation. It seems to be a safe and effective approach and should be tried for recurrent bleeders with septal perforation.

 Ichimura K, Kikuchi H, Imayoshi S, et al: Are patients with severe epistaxis caused by hereditary hemorrhagic telangiectasia satisfied with nostril closure surgery? Auris Nasus Larynx 39:59-64, 2012, doi: 10.1016/j.anl.2011.03.003. Epub 2011 May 17.


Recurrent epistaxis as a manifestation of hereditary hemorrhagic telangiectasia (HHT) is usually difficult  to control. Although no treatment is regarded to be completely efficacious, nostril closure is considered a modality of choice for the most severe cases. The cessation of airflow resulting from this procedure can stop bleeding by minimizing risk factors. However, loss of nasal functions is a disadvantage of nostril closure. We conducted a questionnaire survey of patients who underwent nostril closure surgery, regarding the effects and disadvantages of the operation.


Seven patients were asked questions on issues including frequency and severity of epistaxis pre- and post-operatively, satisfaction of treatment, and impairment in daily living activities.


Most patients reported complete cessation of bleeding. Some still had bleeding, but the frequency and severity were far lower. No transfusions were required in any of the cases. Patients reported some disadvantages, for example, respiratory, olfactory, and phonatory issues. Six out of seven patients were very satisfied with the outcome of surgery.


Nostril closure surgery can remarkably reduce frequency and volume of epistaxis. Our survey indicated that satisfactory results were achieved. However, difficulties caused by complete nasal obstruction varied. Thus, individualized coping strategies are required.

 Nakayama M, Nawa T, Chonan T et al: Prevalence of pulmonary arteriovenous malformations as estimated by low-dose thoracic CT screening. Intern Med 51:1677-1681, 2012

BACKGROUND: Pulmonary arteriovenous malformations (PAVMs) are rarely encountered in clinical practice. The prevalence of PAVMs associated with hereditary hemorrhagic telangiectasia (HHT) has been estimated based on the rate in the family members of HHT patients, but the prevalence of PAVMs in the general population remains unknown.

METHODS: We retrospectively examined the prevalence and clinical characteristics of PAVMs as detected by a low-dose thoracic CT screening program for lung cancer at the Hitachi Medical Center and the Hitachi General Health Care Center in the northern part of Ibaraki Prefecture, Japan.

RESULTS: From 2001 to 2007, we identified eight patients (seven females and one male) with PAVMs among 21,235 initial screening participants (the mean age of the patients with PAVMs and that of the screening participants was 60.6 years). The prevalence of PAVMs was estimated at 38 per 100,000 individuals [95% confidence interval (CI)=18-76]. The diameter of the PAVMs was a mean of 6.6 mm, and none of the lesions could be detected by chest X-ray. Females older than 60 years tended to have larger PAVMs than younger women did (p=0.06). Two patients (25%) were diagnosed with HHT. One patient had previously undergone surgery for a brain abscess.

CONCLUSION: PAVMs are more prevalent than previously reported, especially among females.

 竹田淳恵、藤堂謙一、山本司郎、山上 宏、川本未知、幸原伸夫:遺伝性出血性毛細血管拡張症にともなう肺動静脈瘻を介して奇異性脳塞栓症を発症した1例.臨床神経 52:161-165, 2012


 Kaneko M, Nozawa H, Kitayama J, Sunami E, Akahane M, Yamauchi N, Furukawa Y, Nagawa H: A case of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease) with multiple polyps arising in the cecum and appendix. Acta Gastroenterol Belg 74:352–354, 2011

We present the case of a 32-year-old female with cecal and appendiceal polyps that were removed by laparoscopy-assisted surgery. She also had recurrent nosebleeds due to telangiectases in the nasal mucosa and arteriovenous malformations in the lung, all of which contributed to the diagnosis of hereditary hemorrhagic telangiectasia.