359 research outputs found
First evidence of maternally inherited mosaicism in TGFBR1 and subtle primary myocardial changes in Loeys-Dietz syndrome: a case report
No full textBackground: Loeys-Dietz syndrome (LDS) is a rare multisystemic disorder characterized by vascular and skeletal abnormalities, with considerable intra- and interfamilial variability. Case presentation: We report the case of an 8-year-old male with clinical features of two distinct genetic disorders, namely LDS, manifesting in the first months by progressive aortic root dilatation, arterial tortuosity, bifid uvula, and inguinal hernias and oculocutaneous albinism (OCA) manifesting by white hair and skin that does not tan, nystagmus, reduced iris pigment with iris translucency, and reduced retinal pigment). We identified previously reported, homozygous mutations of TYR, c.1A > G (p.Met1Val) and heterozygous, missense mutation of TGFBR1, c.1460G > A (p.Arg487Gln). Family history revealed that his mother underwent multiple surgical repairs for recurrent hemorrhage originating from the buccal artery. Molecular studies confirmed a maternally inherited low grade TGFBR1 mutation somatic mosaicism (18% in peripheral blood leukocytes, 18% in buccal cells and 10% in hair root cells). Maternal cardiac investigations revealed peculiar cardiovascular features: mild tortuosity at the aortic arch, dilatation of the proximal abdominal aorta, multiple deep left ventricular myocardial crypts, and dysplastic mitral valve. TGFBR2 germline mosaicism has been described in three fathers of children carrying TGFBR2 mutations but, to the best of our knowledge, no case of maternally inherited TGFBR1 mutation mosaicism has been reported so far. Conclusions: This case report suggests that individuals with somatic mosaicism might be at risk for mild and unusual forms of LDS but germline mosaicism can lead to full blown picture of the disease in offspring
Loeys-Dietz syndrome : a possible solution for Akhenaten's and his family's mystery syndrome
No full textAbstract: The presence of a familial disease among royal members of 18th dynasty of the new kingdom who ruled in Egypt from the mid-16th to the early 11th centuries BC has been established, largely prompted by the bizarre body shape of Akhenaten (the iconoclastic pharaoh of this dynasty) and his family, as demonstrated in statues and artwork. It had been thought previously that this was an expression of a revolutionised artistic style that followed radical reforms by Akhenaten of Egyptian society, but recent studies on mummies confirmed the presence of a constellation of corresponding pathologies. Several illnesses have been suggested to solve this enigma; we propose Loeys-Dietz syndrome as a probable diagnosis for this genetic affliction within the royal family
A TURKISH PATIENT OF TYPICAL LOEYS-DIETZ SYNDROME WITH A TGFBR2 MUTATION
No full textA Turkish patient of typical Loeys-Dietz syndrome with a TGFBR2 mutation: We describe a 2-years-old male patient with skeletal, neurological, cardiovascular, and connective tissue anomalies. Skeletal anomalies included pectus excavatum, hammer toes and hallux valgus and camptodactyly. The characteristic craniofacial findings of hypertelorism, down slanting palpebral fissures, strabismus, ptosis of eyelids, bifid uvula, high-arched palate and retrognathia were present. The proband has been operated on twice for bilateral inguinal hernia and several times for his foot deformities. Psychomotor development was retarded. At present, echocardiographic findings show aortic root dilation. The patient has important characteristics of Loeys-Dietz syndrome (LDS). Direct sequencing analysis of the transforming growth factor beta receptor I and II (TGFBR1 and 2) genes was performed and was demonstrated heterozygous missense mutation of the TGFBR2 gene in the patient, which confirms the diagnosis of LDS. This is the first Turkish patient with typical clinical signs of LDS. This report also illustrates that LDS and Shprintzen-Goldberg syndrome (SGS) have some common clinical characteristics
Gastric pseudoaneurysm in the setting of Loey’s Dietz Syndrome
No full textLoey’s Dietz syndrome is a disorder of connective tissue caused by a mutation in the genes that
encode transforming growth factor (TGF) beta receptor 1 and 2.
It is an autosomal dominant
disorder similar to Marfan’s syndrome but with a more aggressive clinical course.
Patients with
Loey’s-Dietz syndrome have progressive dilatation of the aortic root that can lead to aortic
dissection and rupture. The location of non-aortic arterial aneurysms may be wide spread but often
occur in the head and neck vessels.peer-reviewe
Endovascular treatment for type B aortic dissection in a patient with Loeys-Dietz syndorome accompanied by potential lung cancer
No full text論文(Article)Loeys-Dietz syndrome is a recently recognized genetic connective tissue disorder. Aortic involvement in Loeys-Dietz syndrome is known to be more aggressive, even in young patients. Earlierand wider ranging surgical treatment is recommended because of the aggressive nature of its aortic pathology. We report the case of a 17-year-old girl diagnosed with acute type B aortic dissection accompanied by potential lung cancer. Because of rapid enlargement of the dissected aorta, urgent surgical intervention was considered to be mandatory. Considering the possible malignancy of the lung tumor, we reluctantly performed palliative thoracic endovascular aortic repair as an alternative to open surgery. However, endovascular treatment resulted in further expansion of the dissected
aorta. Additional stent graft deployment at downstream aorta was performed and the false lumen flow was decreased significantly. Postoperative computed tomographic examination showed decreased descending aortic diameter with progressive false lumen thrombosis. In patients with Loeys-Dietz syndrome, the application of endovascular therapy should be performed more carefully than expected, especially if there is a reason that open surgery would be unsuitable
Unusual 8p inverted duplication deletion with telomere capture from 8q.(*First two authors contributed equally to this work)
No full textInverted 8p duplication deletions are recurrent chromosomal rearrangements that are mediated through non-allelic homologous recombination (NAHR) between olfactory receptor (OR) gene clusters at 8p23.1. These rearrangements result in a proximal inverted duplication of various extent, a single copy region between the OR gene clusters and a terminal 8p deletion. The terminal deletions are stabilized by direct addition of telomeric repeats, so called telomere healing. Here, we report a patient with an unusual inverted duplication deletion of 8p. Stabilization of the broken chromosome end was achieved by telomere capture instead of telomere healing, resulting in an additional duplication of 8q24.13 -> qter on the short arm of chromosome 8. Moreover, the inverted duplication was only 3.4 Mb in size (restricted to band 8p22) and thus cytogenetically undetectable. To the best of our knowledge this is the smallest inverted duplication reported hitherto. We describe the molecular characterization by FISH and array CGH of this unusual inv dup del (8p) and a previously reported patient with a similar 8q duplication and review the literature on cases associated with telomere capture. (C) 2008 Elsevier Masson SAS. All rights reserved
Complex Multi-Stage Total Aortic and Subclavian Artery Replacement in a 9-year old boy with Loeys-Dietz-Syndrome
No full textBACKGROUND
Loeys-Dietz Syndrome is a rare connective tissue disorder that is associated with arterial pathologies such as aortic dissections, tortuosity and aneurysms.We present a child with Loeys-Dietz Syndrome type 2 that received total aortic and bilateral subclavian artery replacement.
CASE REPORT
A 9-year old boy with Loeys-Dietz Syndrome type 2 and acute type B aortic dissection received an urgent complete thoracic and thoraco-abdominal aortic repair within three days. First, the ascending aorta and aortic root were replaced in a Tirone David and Frozen Elephant Trunk procedure. Then, the descending and supramesenteric aorta was replaced by a Dacron interposition graft with direct implantation of the celiac trunk. During the 15 months follow-up, the patient required three more surgical interventions for rapid expanding aneurysms of both subclavian arteries and the infrarenal aorta. No major adverse event nor secondary interventions occurred. Ultrasonographic and magnetic resonance imaging follow-up is continued at 6-months intervals.
CONCLUSION
Children with Loeys-Dietz Syndrome may require extensive aortic repair for aortic dissection and show rapidly expanding aneurysms. Referral to a center with pediatric vascular expertise and long-term follow-up examinations are crucial
Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome
No full textArterial tortuosity syndrome (ATS) is an autosomal recessive
disorder characterized by tortuosity, elongation, stenosis and
aneurysm formation in the major arteries owing to disruption
of elastic fibers in the medial layer of the arterial wall1.
Previously, we used homozygosity mapping to map a candidate
locus in a 4.1-Mb region on chromosome 20q13.1 (ref. 2).
Here, we narrowed the candidate region to 1.2 Mb containing
seven genes. Mutations in one of these genes, SLC2A10,
encoding the facilitative glucose transporter GLUT10, were
identified in six ATS families. GLUT10 deficiency is associated
with upregulation of the TGFb pathway in the arterial wall, a
finding also observed in Loeys-Dietz syndrome, in which aortic
aneurysms associate with arterial tortuosity3. The identification
of a glucose transporter gene responsible for altered arterial
morphogenesis is notable in light of the previously suggested
link between GLUT10 and type 2 diabetes4,5. Our data
could provide new insight on the mechanisms causing
microangiopathic changes associated with diabetes and
suggest that therapeutic compounds intervening with
TGFb signaling represent a new treatment strategy
Imaging and Clinical Features in a Child with Loeys-Dietz Syndrome: A Case Report
No full textWe describe a boy with Loeys-Dietz syndrome (LDS) a genetic and recently described condition that affects connective tissues belonging to a group of Marfan-related disorders. Since there are only a few cases reported misdiagnosis may not be uncommon. Radiological findings in our patient include pectus excavatum, aortic root dilatation, diffuse dilatation of the intracerebral vessels and a Chiari I malformation. We describe the imaging findings, clinical presentation and diagnosis criteria of this entity
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