Contribution of VANGL2 mutations to isolated neural tube defects

Kibar Z, Salem S, Bosoi CM, Pauwels E, De Marco P, Merello E, Bassuk AG, Capra V, Gros P. Contribution of VANGL2 mutations to isolated neural tube defects. Vangl2 was identified as the gene defective in the Looptail (Lp) mouse model for neural tube defects (NTDs). This gene forms part of the planar cell polarity (PCP) pathway, also called the non‐canonical Frizzled/Dishevelled pathway, which mediates the morphogenetic process of convergent extension essential for proper gastrulation and neural tube formation in vertebrates. Genetic defects in PCP signaling have strongly been associated with NTDs in mouse models. To assess the role of VANGL2 in the complex etiology of NTDs in humans, we resequenced this gene in a large multi‐ethnic cohort of 673 familial and sporadic NTD patients, including 453 open spina bifida and 202 closed spinal NTD cases. Six novel rare missense mutations were identified in seven patients, five of which were affected with closed spinal NTDs. This suggests that VANGL2 mutations may predispose to NTDs in approximately 2.5% of closed spinal NTDs (5 in 202), at a frequency that is significantly different from that of 0.4% (2 in 453) detected in open spina bifida patients (p = 0.027). Our findings strongly implicate VANGL2 in the genetic causation of spinal NTDs in a subset of patients and provide additional evidence for a pathogenic role of PCP signaling in these malformations.     

Blood patch treatment of chylothorax following transthoracic oesophagogastrectomy: a novel technique to aid surgical management

Chylothorax is a well-recognised complication of oesophagectomy, occurring in around 3% of cases. If managed conservatively, the mortality rate can be over 50%. We describe our experience of managing a patient with a chylothorax following oesophagectomy, and the use of a blood patch (a novel technique) to overcome persistent leakage following re-operation. The authors feel that this technique has the potential for a wider application in the treatment of chyle leak, especially if combined with minimally invasive or radiological techniques.     

Assessment of right ventricular systolic function using tricuspid annular-plane systolic excursion in Nigerians with systemic hypertension

Aim

Right ventricular (RV) systolic function in patients with hypertensive heart disease (HHD) is not well characterised. The primary aim of this study was to assess the systolic function of the right ventricle in patients with HHD using tricuspid annular-plane systolic excursion (TAPSE).

Methods

The study was cross-sectional in design and carried out in Kano, Nigeria. Patients were recruited if they had HHD on echocardiography and were at least 15 years of age. Patients with other cardiac pathologies such as ischaemic and valvular heart diseases were excluded. Patients were considered to have abnormal RV systolic function if they had reduced values of TAPSE (< 15 mm). A p-value of < 0.05 was considered statistically significant.

Results

A total of 186 patients were serially recruited over seven months. Of these, 131 (70.4%) had normal RV systolic function (group 1) and 55 patients (29.6%) had abnormal function (group 2). Group 2 patients were older (p = 0.002) and had a higher prevalence of peripheral oedema (p = 0.002), moderate to severe dyspnoea, higher heart rate and lower left ventricular ejection fraction (p < 0.001). Atrial arrhythmias were also more prevalent among group 2 patients (p < 0.05). The best correlate to TAPSE was the septal mitral annularplane systolic excursion (r = +0.541, p < 0.001). Several variables such as age predicted the presence of reduced TAPSE.

Conclusion

The study found that almost one-third of patients with HHD in Kano had RV systolic dysfunction as defined by reduced TAPSE, and these patients had a greater prevalence of factors associated with morbidity and mortality.     

Impfungen in der frauenärztlichen Praxis – Teil 2

Diseases which can be prevented by vaccination and the indications for vaccination are described in detail with a special focus on aspects relevant for the gynecological and obstetric practice. The article also gives the billing numbers for Germany which are necessary for the remuneration. With this vaccinations can be implemented in the routine daily practice. The gynecologist entrusted by the patient can provide vaccination protection in all phases of life, if necessary even during pregnancy and provide neonates with maternal passive immunity.     

Marginal papular acrokeratodermas: no racial limitations for a clinical spectrum that responds to acitretin

Marginal papular acrokeratoderma (MPA) encompasses a group of disorders that share crateriform, keratotic papules along the margins of the hands and feet. We report a unique case of a Philippino woman, with focal acral hyperkeratosis (FAH) associated with sensorineural hearing loss. The clinical phenotype of FAH (hereditary MPA without elastorrhexis) is expanded and the hypothesis of a racially limited disorder is weakened. Effective treatment of this embarrassing condition with acitretin is demonstrated.     

Biomechanische Zustand der Hornhaut als neuer Indikator für pathologische und strukturelle Veränderungen

Aim

Several methods permit the measurement of geometric parameters of the cornea, but until now biomechanical conditions of the cornea have been ignored (e.g. in refractive corneal surgery). Besides the geometric condition, biomechanical properties of the cornea have been shown to influence applanation measurement of intra-ocular pressure (IOP) and epidemiological studies have identified corneal thickness as an independent risk factor for the development and progression of glaucoma. The aim of this investigation was to characterize the biomechanical properties of the cornea using the ocular response analyzer (ORA).

Methods

The ocular response analyzer (ORA) is a new method available for non-contact measurement of the biomechanical properties of the cornea. We evaluated the reproducibility of measurements, the difference between static and dynamic factors and the impact of independent factors (e.g. IOP, age, CCT, swelling of the cornea) on 2,500 measurements of corneal hysteresis (CH) and corneal resistance factor (CRF).

Results

In a large sample size we observed changes in CH and CRF after refractive surgery procedures (LASIK, UV-A cross-linking, keratoplasty) and in other corneal disorders (keratoconus, corneal dystrophies).

Conclusions

CRF and CH changes may reflect structural changes of the cornea. Thus, the ORA provides valuable information for a better understanding and characterization of the biomechanical condition of the cornea, especially with regard to diseases such as keratoconus and glaucoma.