Two fetuses in one family of arterial tortuosity syndrome: prenatal ultrasound diagnosis.

BACKGROUND: Arterial tortuosity syndrome (ATS) is a rare autosomal recessive connective tissue disorder chiefly characterized by elongated and tortuosity of the large and medium sized arteries and anomalies of the vascular elastic fibers. Here we reported cases of brother about ATS from the same family on the prenatal ultrasound diagnosis. Reports of this case are rare in antenatally and we draw the vessel simulated diagram to display visually. CASE PRESENTATION: Prenatal ultrasound scanning at 29 weeks of gestation of the first fetus showed obvious tortuous and elongated of the aortic arch, ductus arteriosus, left and right pulmonary arteries, carotid and subclavian arteries. Three months after delivery, Contrast-enhanced computed tomography images (CTA) were performed to clearly display vascular abnormalities consistent with prenatal diagnosis of ultrasound. Whole exome sequencing (WES) was performed eight months after birth, two heterozygous variants of SLC2A10 gene was detected in newborn and their father and mother, respectively. Prenatal ultrasound scan at 22 weeks of gestation of the second fetus showed similar cardiovascular imaging. After birth the siblings have facial characteristic features gradually as aging. No surgical intervention was performed in the siblings follow up 19 months. CONCLUSIONS: The key points of prenatal ultrasound diagnosis of ATS are the elongation and tortuosity of the large and medium sized arteries. Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions.

Spotted bones in an osteopoikilosis-related disease (Buschke Ollendorff Syndrome): Identifying this rare condition from the lab to the field.

OBJECTIVE: To improve the differential diagnosis of osteopoikilosis in past populations using a clinical case as an example of this rare condition. MATERIALS: A patient referred to our Genetic Service with suspected Buschke Ollendorff Syndrome after finding a connective nevus. METHODS: Radiological images from different body regions were accompanied by a genetic study using next-generation sequencing. RESULTS: Small circular-to-ellipsoid sclerotic lesions were found in the epiphysis and metaphysis of long bones, as well as in the pelvis. These lesions were bilaterally distributed and with well-defined margins, compatible with the characteristics of Buschke Ollendorff Syndrome, bone manifestation osteopoikilosis. A heterozygous mutation on LEMD3 (NM_001167614:c.1918 + 1G > C) was identified by next-generation sequencing. Based on this confirmed case, we have discussed the most probable causes of similar bone lesions found in the archaeological record. CONCLUSION: It has been demonstrated how a current case of a rare disease can provide useful tools to improve the differential diagnosis of this disease in ancient skeletons. SIGNIFICANCE: This work underlines the great need for multidisciplinary platforms that integrates clinical research into paleopathology in order to successfully address the study of rare diseases from the past. LIMITATIONS: Since OPK is only detected by X-rays, suspected cases of this bone lesion will only be identified when radiographs are taken for other purposes. SUGGESTIONS FOR FURTHER RESEARCH: Retrospective and large-scale studies of radiographs from other research in past populations.

Does Carotid Artery Tortuosity Play a Role in Stroke?

PURPOSE: To explore the association between carotid artery length and tortuosity, and the occurrence of stroke. MATERIAL AND METHODS: In this retrospective study, IRB approved, 411 consecutive patients (males: 245; median age: 56 ± 12 years, age range: 21-93 years) with anterior circulation ischemic stroke were included. Only patients that underwent CTA within 7 days were considered and stroke caused by cardiac embolism and thoracic aorta embolism were excluded. For each patient, both carotid arteries were considered, and the ICA, CCA-ICA length and tortuosity were calculated. Inter-observer analysis was quantified with the Bland-Altman test. Mann-Whitney test and logistic regression analysis were also calculated to test the association between length and tortuosity with the occurrence of stroke. RESULTS: In the final analysis, 166 patients (males: 72; median age: 54 ± 12 years, age range: 24-89 years) with anterior circulation ischemic stroke that were admitted to our hospital between February 2008 and December 2013 were included. The results showed a good concordance for the length of the vessels with a mean variation of 0.7% and 0.5% for CCA-ICA and ICA length respectively an for the tortuosity with a mean variation of 0.2% and -0.4% for CCA-ICA and ICA respectively. The analysis shows a statistically significant association between the tortuosity index of the ICA and CCA-ICA sides with stroke (P value = 0.0001 in both cases) and these findings were confirmed also with the logistic regression analysis. CONCLUSION: Results of this study suggest that tortuosity index is associated with the presence of stroke whereas the length of the carotid arteries does not play a significant role.

Increased Internal Carotid Artery Tortuosity is a Risk Factor for Spontaneous Cervicocerebral Artery Dissection.

OBJECTIVE: Spontaneous cervicocerebral artery dissection (sCCD) is an important cause of ischaemic stroke that often occurs in young and middle aged patients. The purpose of this study was to investigate the correlation between tortuosity of the carotid artery and sCCD. METHODS: Patients with confirmed sCCD who underwent computed tomography angiography (CTA) were reviewed retrospectively. Age and sex matched patients having CTA were used as controls. The tortuosity indices of the cervical arteries were measured from the CTA images. The carotid siphon and the extracranial internal carotid artery (ICA) were evaluated according to morphological classification. The carotid siphons were classified into five types. The extracranial ICA was categorised as simple tortuosity, coiling or kinking. Independent risk factors for sCCD were investigated using multivariable analysis. RESULTS: The study included sixty-six patients with sCCD and 66 controls. There were no differences in vascular risk factors between the two groups. The internal carotid tortuosity index (ICTI) (25.24 ± 12.37 vs. 15.90 ± 8.55, respectively; p < .001) and vertebral tortuosity index (VTI) (median 11.28; interquartile range [IQR] 6.88, 18.80 vs. median 8.38; IQR 6.02, 12.20, respectively; p = .008) were higher in the patients with sCCD than in the controls. Type III and Type IV carotid siphons were more common in the patients with sCCD (p = .001 and p < .001, respectively). The prevalence of any vessel tortuosity, coiling and kinking of the extracranial ICA was higher in the patients with sCCD (p < .001, p = .018 and p = .006, respectively). ICTI (odds ratio [OR] 2.964; p = .026), VTI (OR 5.141; p = .009), and Type III carotid siphons (OR 4.654; p = .003) were independently associated with the risk of sCCD. CONCLUSION: Arterial tortuosity is associated with sCCD, and greater tortuosity of the cervical artery may indicate an increased risk of arterial dissection.

Clinical presentation, sonographic features and treatment options of segmental stiff skin syndrome.

Segmental stiff skin syndrome is a rare genetic connective tissue disease, which is often misdiagnosed. High-frequency ultrasonography can represent a useful clinical adjunct in the differential diagnosis of this condition, in conjunction with the clinical and histopathological findings. Treatment options are limited and evidence is scarce. We present the clinical, sonographic and histological features of five paediatric patients diagnosed at our institution and discuss their response to treatment.

First antenatally confirmed case of arterial tortuosity syndrome.

Arterial tortuosity syndrome (ATS) is a rare, autosomal recessive, connective tissue disorder. It predominantly involves the arterial tree with clinical features reflecting the systems involved. There have been few cases of ATS suspected during antenatal screening ultrasound in high-risk families, but none confirmed. We present the first case of ATS confirmed antenatally in the fetus with cascade testing, detecting the disease in the mother as well.

Pro-Fibrotic Phenotype in a Patient with Segmental Stiff Skin Syndrome via TGF-ß Signaling Overactivation.

Transforming growth factor ß (TGF-ß) superfamily signaling pathways are ubiquitous and essential for several cellular and physiological processes. The overexpression of TGF-ß results in excessive fibrosis in multiple human disorders. Among them, stiff skin syndrome (SSS) is an ultrarare and untreatable condition characterized by the progressive thickening and hardening of the dermis, and acquired joint limitations. SSS is distinct in a widespread form, caused by recurrent germline variants of FBN1 encoding a key molecule of the TGF-ß signaling, and a segmental form with unknown molecular basis. Here, we report a 12-year-old female with segmental SSS, affecting the right upper limb with acquired thickening of the dermis evident at the magnetic resonance imaging, and progressive limitation of the elbow and shoulder. To better explore the molecular and cellular mechanisms that drive segmental SSS, several functional studies on patient's fibroblasts were employed. We hypothesized an impairment of TGF-ß signaling and, consequently, a dysregulation of the associated downstream signaling. Lesional fibroblast studies showed a higher phosphorylation level of extracellular signal-regulated kinase 1/2 (ERK1/2), increased levels of nuclear factor-kB (NFkB), and a nuclear accumulation of phosphorylated Smad2 via Western blot and microscopy analyses. Quantitative PCR expression analysis of genes encoding key extracellular matrix proteins revealed increased levels of COL1A1, COL3A1, AGT, LTBP and ITGB1, while zymography assay reported a reduced metalloproteinase 2 enzymatic activity. In vitro exposure of patient's fibroblasts to losartan led to the partial restoration of normal transforming growth factor ß (TGF-ß) marker protein levels. Taken together, these data demonstrate that in our patient, segmental SSS is characterized by the overactivation of multiple TGF-ß signaling pathways, which likely results in altered extracellular matrix composition and fibroblast homeostasis. Our results for the first time reported that aberrant TGF-ß signaling may drive the pathogenesis of segmental SSS and might open the way to novel therapeutic approaches.

Síndrome de tortuosidad arterial en un paciente pediátrico / Arterial tortuosity syndrome in a paediatric patient

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Trichoscopy findings in dissecting cellulitis.

Dissecting cellulitis is an inflammatory, chronic, and recurrent disease of the hair follicles that mainly affects young Afro-descendent men. Trichoscopy is a method of great diagnostic value for disorders of the scalp. Clinical and trichoscopic findings of dissecting cellulitis are heterogeneous and may present features common to non-cicatricial and scarring alopecia. This article presents the trichoscopic findings of dissecting cellulitis that help in the diagnosis and consequent institution of the appropriate therapy and better prognosis of the disease.

Trichoscopy findings in dissecting cellulitis

Abstract Dissecting cellulitis is an inflammatory, chronic, and recurrent disease of the hair follicles that mainly affects young Afro-descendent men. Trichoscopy is a method of great diagnostic value for disorders of the scalp. Clinical and trichoscopic findings of dissecting cellulitis are heterogeneous and may present features common to non-cicatricial and scarring alopecia. This article presents the trichoscopic findings of dissecting cellulitis that help in the diagnosis and consequent institution of the appropriate therapy and better prognosis of the disease.

Vascular tortuosity of the internal carotid artery is related to the RNF213 c.14429G > A variant in moyamoya disease.

Recent studies have implicated RNF213 mutations in the pathogenesis of moyamoya disease (MMD). However, the underlying mechanism of disease development is not fully elucidated. Nonetheless, a possible relationship between vascular morphology and hemodynamics related with MMD has been proposed. Here, we aimed to investigate the relationship between a variant of RNF213 and the morphology of the internal carotid artery (ICA). We enrolled bilateral MMD patients who had undergone genetic testing for RNF213. Patients were divided into mutant and wild-type groups. Six anatomy-specific three-dimensional coordinates were collected using magnetic-resonance angiography. From these, five vectors between two adjacent points and four angles between two adjacent vectors were calculated. The tortuosity was defined as the ratio between the actual and the linear length of the ICAs. Among 58 patients, 44 and 14 belonged to the mutant and wild-type groups, respectively. The tortuosity of ICAs was significantly lower in the mutant group (p = 0.010). The change in blood flow direction was more prominent in the wild-type group (p = 0.002). The tortuosity was significantly lower in MMD patients than normal controls (p < 0.001). Our results indicate that RNF213 could play a role in the lower tortuosity observed in patients with RNF213 mutation.

Hybrid Arch Frozen Elephant Trunk Repair of Complex Arch Aneurysm With Severe Arterial Tortuosity.

Patients with complex aortic arch aneurysms and severe arterial tortuosity represent a unique challenge because of extreme angulations, mixed aneurysm and stenotic disease, and fragile tissues. Novel hybrid arch frozen elephant trunk techniques can expand surgical repair options to include single-stage, complete aortic reconstruction via sternotomy alone, without the need for simultaneous thoracotomy or clamshell incisions. We describe successful hybrid aortic arch reconstruction with Thoraflex Hybrid graft in a patient with complex arch aneurysm and severe arterial tortuosity.