A pedigree study of Loeys-Dietz syndrome type 4 with skeletal deformity related to a novel TGFβ2 mutation / 中华内科杂志

Objective:Loeys-Dietz syndrome is a rare type of hereditary connective tissue disease. This study was aimed to analyze the clinical characteristics and gene mutations in a family of Loeys-Dietz syndrome with skeletal deformity.Methods:Clinical data of the proband and family members were collected and biochemical measurements and radiological examinations were conducted. Genomic DNA was extracted from peripheral blood of the family members. Whole-exome sequencing was performed to determine the mutation sites in the proband, and Sanger sequencing was applied to verify the candidate mutation in the other family members.Results:The proband is a 34-year-old man with deformities of lower extremities for more than 30 years. Physical examinations showed dolichostenomelia, pes planus, joint laxity and scoliosis. Echocardiography revealed the dilatation of aortic root at the level of the sinuses of Valsalva. A heterozygous missense mutation (c. 220A>C, p.Thr74Pro) in exon 1 of TGFβ2 gene was identified in the proband. The same mutation was detected in his sister and niece with similar clinical features such as deformities of lower extremities and pes planus. This novel mutation has not been reported in ExAC or 1000G and was predicted to be deleterious, supporting a diagnosis of Loeys-Dietz syndrome type 4.Conclusions:Loeys-Dietz syndrome type 4 is caused by TGFβ2 mutations. Skeletal deformity is one of the distinctive features. Genetic testing is helpful for the early diagnosis and differential diagnosis from other connective tissue diseases.

Novel Association of a Familial TGFBR1 Mutation in Loeys-Dietz Syndrome with Concomitant Hematologic Malignancy / 대한흉부외과학회지

Concomitant Loeys-Dietz syndrome (LDS) and hematologic malignancies are exceptionally rare. This is the first report of a patient operated on for aortic root dilation who had been previously diagnosed with LDS and B-cell-lymphoma. After completion of chemotherapy and complete remission, an elective valve-sparing aortic root replacement (using the David-V method) was performed. Due to the positive family history, pre-operative genetic counseling was conducted, and revealed LDS with a TGFBR1 (transforming growth factor beta receptor type I) mutation in 6 probands of the family, albeit in 1 of them posthumously. This missense mutation has been previously described in relation to aortic dissection, but a causative relationship to malignancy has so far neither been proposed nor proven.

A Case of Total Arch Replacement for Non-anastomotic Pseudoaneurysm by Proximal Stent Graft Induced-Vascular Graft Perforation in Loeys-Dietz Syndrome after Total Aortic Replacement / 日本心臓血管外科学会雑誌

A 26-year-old lady with Loeys Dietz syndrome had undergone 5 consecutive operations from 2007 to 2014. Finally, her total aorta was replaced by vascular grafts and stent grafts. The patient was admitted to our hospital with headache and dizziness in 2016. Computed tomography showed a giant pseudoaneurysm at the aortic arch with extravasation from the vascular graft. The proximal flares of thoracic stent grafts caused perforation of thoracic vascular grafts. Cerebral perfusion was not sufficient, because this aneurysm compressed the innominate, left carotid and left subclavian arteries. Decreasing of cerebral perfusion caused headache and dizziness. We performed total arch replacement. We started extracorporeal circulation before median sternotomy but the aneurysm ruptured during median sternotomy. We controlled the bleeding by manual compression and immediately started selective cerebral perfusion and induced cardiac arrest. After opening the distal portion, we cut down the proximal flares of thoracic stent graft and inserted an elephant trunk into the stent graft. We sutured between the new vascular graft and the stent graft and covered the suture line with another short vascular graft. As a result we could protect the vascular graft from the stent graft. Computed tomography demonstrated that the pseudoaneurysm and extravasation disappeared. Cerebral perfusion increased and the patient's symptoms improved. Postoperatively the patient was discharged from our hospital without any major complications at POD 11.

Síndrome de Loeys-Dietz, 3 generaciones, 4 casos familiares / Loeys-Dietz Syndrome, 3 generations, 4 familial cases

El síndrome de Loeys-Dietz es una enfermedad genética autosómica dominante caracterizada por aneurismas aórticos, tortuosidad arterial generalizada, hipertelorismo y úvula bifida o paladar hendido. La complicación cardiovascular más grave es la disección aórtica. Se presentan cuatro casos familiares de este síndrome en tres generaciones, todos con dilatación aórtica grave, y se describen sus aspectos diagnósticos, indicación y tratamiento quirúrgico, como así también pautas de seguimiento.

Loeys-Dietz Syndrome is an autosomal dominant disease with aortic aneurysms, arterial tortuosity with hypertelorism and bifid uvula. We describe four familial cases within three generations. The diagnosis, surgical management and followup will be addressed.

Aortic Arch Aneurysm 7 Years after Aortic Root Replacement in a Patient of Loeys-Dietz Syndrome / 日本心臓血管外科学会雑誌

<p>A 14-year-old women who had a history of aortic root replacement at 7 years old admitted our hospital due to dilatation of aortic arch aneurysm. Loeys-Dietz syndrome was diagnosed when she was 10 years old. Computed tomography showed 70 mm proximal arch aneurysm. Operative findings revealed brachiocephalic artery and left common carotid artery branched from aneurysm. Partial arch replacement was performed and distal anastomosis was made between left common carotid artery and left subclavian artery. Close observation by CT regularly is necessary and undergo aortic repair not to miss the timing of surgery.</p>

Síndrome de Loeys-Dietz, una mutación en el gen TGFBR2, primer reporte en el suroccidente colombiano / Loeys-Dietz syndrome, a mutation in TGFBR2 gene, first report in the colombian suroccident

Resumen: el síndrome de Loeys-Dietz es una rara enfermedad genética, autosómica dominante, con hábito marfanoide, que pertenece a un subconjunto de enfermedades del tejido conectivo con afectación esquelética, ocular y cardiovascular, principalmente. El desarrollo de aneurismas es característico en esta patología. El síndrome de Loeys-Dietz es causado por mutaciones en los genes TGFBR1, TGFBR2, TGFB2, TGFB3 Y SMAD3. En este manuscrito se describe el caso clínico de un paciente masculino, de 22 meses de vida, con una dilatación importante de la raíz aórtica y arco aórtico elongado cuya prueba molecular confirma el diagnóstico de síndrome de Loeys-Dietz, asociado a una mutación en el gen TGFBR2. Este corresponde al primer caso reportado en el suroccidente colombiano. (AU)

Abstract: Loeys-Dietz syndrome is a rare, autosomal dominant genetic disease, with marfanoid habit, which belongs to a subset of diseases of the connective tissue with mainly skeletal, ocular, and cardiovascular involvement. Aneurysms development is characteristic in this pathology. Loeys-Dietz syndrome is caused by mutations in TGFBR1, TGFBR2, TGFB2, TGFB3 and SMAD3 genes. In this manuscript is presented the clinical case of a 22-month-old male patient with significant dilatation of the aortic root and elongated aortic arch is described. The molecular test confirms the diagnosis of Loeys-Dietz syndrome associated with a mutation in the TGFBR2 gene. This corresponds to the first case reported in the southwestern Colombian. (AU)

A Case of Frozen Elephant Trunk Technique for Aortic Dissection in Loeys-Dietz Syndrome / 日本心臓血管外科学会雑誌

The patient was a 37 year-old man. We diagnosed Loeys-Dietz syndrome based on his physical characteristics that were widely spaced eyes and brachycephaly etc. Since he developed De Bakey III b aortic dissection 3 months later, he needed surgical repair for saccular-shaped distal arch aortic aneurysm. We performed total aortic arch replacement for the aneurysm and valve-sparing aortic root reconstruction for dilatation of the Valsalva sinus. Furthermore we performed the frozen elephant trunk technique for residual aortic dissection at the same time. After 18 months from the operation, we were able to recognize by computed tomography that the false lumen of the aorta next to the stent graft was thrombosed and absorbed and finally disappeared. The stent graft treatment for patients with connective tissue disease might be an effective method and deserves more attention.

Total Arch Replacement for Acute Type A Aortic Dissection 5 Years after Aortic Valve-Sparing Operation in a 14-Year-Old Boy with Loeys-Dietz Syndrome / 日本心臓血管外科学会雑誌

A 14-year-old boy who underwent aortic valve-sparing operation for annuloaortic ectasia at the age of 9 was referred to our service with a diagnosis of acute type A aortic dissection. Emergency total arch replacement with the elephant trunk technique was done successfully and the postoperative course was uneventful. However, computed tomography (CT) 2 weeks after the operation showed a new dissection and enlargement in left subclavian artery and folded elephant trunk. Dilatation in coronary buttons were also seen since the time of surgery. No residual dissection was found in the aorta. Careful follow up is necessary for this case due to multiple aneurysmal changes and a new dissection lesion in a short period. Loeys-Dietz syndrome (LDS) is characterized by vascular findings (aortic aneurysm and dissection) and skeletal manifestations. Due to aortic dissection occurring in smaller diameter aortas in LDS patients than in Marfan syndrome, early and aggressive surgery is recommended for patients with LDS.

Valve Sparing Aortic Root Replacement in Children with Loeys-Dietz Syndrome

Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder that is characterized by aggressive arterial and aortic disease, often involving the formation of aortic aneurysms. We describe the cases of two children with LDS who were diagnosed with aortic root aneurysms and successfully treated by valve-sparing aortic root replacement (VSRR) with a Valsalva graft. VSRR is a safe and suitable operation for children that avoids prosthetic valve replacement.

Multiple Aortic Operations in Loeys-Dietz Syndrome: Report of 2 Cases

Due to its low prevalence and because there is lack of awareness about it, Loeys-Dietz syndrome is often mis-diagnosed as Marfan syndrome, which has similar skeletal abnormalities and aortic pathology. However, the differential diagnosis between these two connective tissue diseases is critical because they correspond to different surgical indications and surgical decision-making. We report two cases of successful thoracoabdominal aortic replacement in patients with previously undiagnosed Loeys-Dietz syndrome.

Aneurismas de aorta abdominal e ilíaca y síndrome de Loeys- Dietz / Abdominal aortic iliac aneurysms and Loeys-Dietz syndrome

Se presenta el caso clínico de una paciente de 29 años de edad, con antecedentes de ectasia aórtica, quien había sido estudiada a los 18 años mediante cineangiografía y se halló un aneurisma fusiforme de la aorta abdominal infrarrenal y de la arteria ilíaca primitiva izquierda, de causa no precisada, las cuales fueron sustituidas con derivación aortofemoral izquierda. Posteriormente, en el 2012, presentó dolor y aumento del volumen en la región inguinal izquierda, por lo que fue atendida en el Cuerpo de Guardia del Hospital Provincial Docente Clinicoquirúrgico "Saturnino Lora Torres" de Santiago de Cuba, y evaluada por especialistas del Servicio de Angiología y Cirugía Vascular, los cuales determinaron operarle de urgencia, al observar un aneurisma anastomótico de la arteria femoral izquierda, de causa micótica, y las características: craneosinostosis, úvula bífida y hendidura del paladar; propias del síndrome de Loeys-Dietz.

The case report of a 29 year-old patient, with a history of aortic ectasia who had been studied when she was 18 years through cineangiography is presented and a fusiform aneurysm of the infrarrenal abdominal aorta and of the left primitive iliac artery, of unspecific cause was found, which were substituted with left aortofemoral bypass. Later on, in 2012, she presented pain and increase of the volume in the left inguinal region, reason why she was assisted in the emergency room of "Saturnino Lora Torres" Teaching Provincial Clinical Surgical Hospital in Santiago de Cuba, and evaluated by specialists of the Angiology and Vascular Surgery Service, which determined to treat her with an emergency surgery, when observing an anastomotic aneurysm of the left femoral artery of fungal cause, and the characteristics: craneosinostosis, bifid uvula and cleft palate; characteristic of Loeys Dietz syndrome.

Aortic Valve-Sparing Operation in a 8 Years Old Boy with Loeys-Dietz Syndrome with Annuloaortic Ectasia / 日本心臓血管外科学会雑誌

An 8 year-old boy had a cardiac murmur pointed out on day three after birth and was given a diagnosis of ventricular septal defect (VSD). He underwent VSD patch closure at two months after birth. He was also found the having Loeys-Dietz syndrome on the basis of mutation of <i>TGFBR2 </i>and physical examination at the age of 2 years. He had been followed up at pediatrics clinic of our hospital since then, and was hospitalized for a 46.5-mm extension of valsalva sinus diameter and moderate aortic insufficiency. The aortic valve was three-cusped and had no abnormality. We performed valve-sparing aortic root replacement. He was discharged on day 18 after the operation without any problems in the postoperative course. Use of an artificial heart valve for the surgery of the aortic root lesion in childhood will probably cause reoperation in the future and difficulty in Warfarin anticoagulation control. A careful decision is needed in the choice of an operation method. Valve-sparing aortic root replacement is a useful operation for patients without aortic valve abnormality.

Neurovascular Manifestation of Loeys-Dietz Syndrome: A Case Report

Loeys-Dietz syndrome (LDS) is an autosomal dominant disorder caused by heterozygous mutations in the genes encoding transforming growth factor-beta receptor type 1 or 2. It is typically characterized by a triad of hypertelorism, cleft palate or bifid uvula, and arterial tortuosity with aneurysm or dissection. Characteristic vascular abnormalities such as tortuosity, aneurysms, dissections, and stenosis are the most severe complications of LDS and can occur in the neurovascular system. We report a 5-year-old boy who presented with headaches and neurovascular abnormalities and was diagnosed with LDS with a novel mutation of the TGFBR1 gene. It is the first Korean report of neurovascular abnormalities in LDS.

A Case of Loeys-Dietz Syndrome That Caused Rapid Enlargement of the Distal Aortic Arch Following Aortic Surgery for Acute Type A Aortic Dissection / 日本心臓血管外科学会雑誌

Loeys-Dietz syndrome (LDS) is characterized by vascular findings (aortic aneurysms and dissections) and skeletal manifestations. Since aortic dissection occurs at smaller aortic diameters than observed in Marfan syndrome, early and aggressive surgery is recommended for patients with LDS. A 45-year-old man who underwent aortic valve replacement for aortic regurgitation at the age of 33 was transferred to our hospital with the diagnosis of acute aortic dissection. We performed emergeny ascending aortic replacement, and suspected LDS because of his specific physical characteristics after surgery. His postoperative course was uneventful, however, computed tomography (CT) performed at 2 weeks after operation showed the new entry at the distal anastomotic site, patent false lumen of the descending aorta and rapid enlargement of the distal aortic arch. Therefore, we performed total arch replacement with the elephant trunk method at 3 weeks after the emergency operation. Mutation of the TGFBR2 gene was found and we finally diagnosed LDS. One year after, complete thrombosis of the false lumen of the descending aorta and decrease in size of the distal aortic arch was observed by CT.

A Case of Near Total Aortic Replacement in an Adolescent With Loeys-Dietz Syndrome

Loeys-Dietz syndrome is a recently described autosomal dominant disorder caused by mutations in the genes for transforming growth factor-beta receptor type 1 or 2 (TGF-ssR 1/2). The syndrome predisposes patients to aortic aneurysm and dissections, along with craniofacial and musculoskeletal abnormalities. Here we report the case of an adolescent who underwent serial near total aortic replacement, from the aortic valve to the descending aorta. Loeys-Dietz syndrome was confirmed in this case by the detection of a mutation in the TGF-ssR 2 gene.

Anesthetic managements for correction of aortic valve regurgitation in a patient with Loeys-Dietz Syndrome: A case report / 대한마취과학회지

Loeys-Dietz Syndrome (LDS) is a recently described autosomal dominant aortic aneurysm syndrome with widespread systemic involvement. It is characterized by the triad of 1) arterial tortuosity and aneurysms, 2) hypertelorism, and 3) bifid uvula or cleft palate. A 12-year-old boy with LDS was scheduled to undergo correction of aortic valve regurgitation due to aortic annuloectasia. We report our clinical experiences of a case of LDS patient with brief review of related literatures and relevant anesthetic problems.