Prenatal diagnosis of Noonan syndrome in fetuses with increased nuchal translucency and a normal karyotype.

OBJECTIVE: Noonan syndrome (NS), one of the most common RASopathies, has an estimated incidence of 1 in 1,000-2,500 live births. In the prenatal period increased nuchal translucency, hygroma colli, hydrops fetus, congenital heart disease, kidney defects, larger amount of amniotic fluid can be observed in affected fetuses with this syndrome. In the fetuses with normal karyotype and no microdeletion/microduplication syndromes the examination of selected genes for RASopathies was added. The aim of the study was to evaluate the clinical benefit of massively parallel sequencing (MPS) of susceptible fetal DNA for NS, i.e., the diagnostic yield on the one hand and the proportion of detected variants of unknown significance (VOUS) on the other. DESIGN: Clinically diagnostic. SETTING: Centrum prenatální diagnostiky, Brno, s.r.o; Cytogenetická laboratoř Brno, s.r.o. METHODS: Samples of amniotic fluid or chorionic villus were analyzed. Selected genes associated with RASopathies were analyzed in case of the negative result of karyotype and array-CGH. A panel of twenty genes was investigated by MPS. RESULTS: In the two-years period, Noonan syndrome was detected in 10 from 95 investigated fetuses. This represents a 10.5% diagnostic efficiency of the method. DNA variants of unknown significance were detected in 10 fetuses. A segregation analysis helped to clarify their meaning in six fetuses. CONCLUSION: MPS allows fast molecular-genetic diagnosis of RASopathies already in the prenatal period. This method contributes to the clarification not only of phenotypic manifestations in already born individuals but also of ultrasound findings in fetuses with both normal karyotype and aCGH.

[Pars Plicata Vitrectomy in Premature Newborns for Retinal Detachment as a Result of Retinopathy of Prematurity, our Results]. / Pars plicata vitrektomie u nedonosených novorozencu pro odchlípení sítnice v dusledku retinopatie nedonosených, nase výsledky.

INTRODUCTION: The aim of this work is to evaluate our own results of surgical treatment of retinal detachment in immature newborns. Retinopathy of prematurity (ROP) is one of the most complicated ocular disorders, both in terms of diagnosis and therapy. It is a potentially blinding illness that arises from the incomplete development of the bloodstream of the neuroretina of preterm infants. Currently, the most effective therapy is ablation of the avascular retina by laser photocoagulation or cryocoagulation. Despite this treatment, the immature retina may develop it´s detachment. METHODOLOGY: We report 2 case-reports, retrospective results of 4-eyes in 2 patients with severe ocular and overall complications of prematurity. The ocular background of preterm babies was investigated in arteficial mydriasis by an indirect ophthalmoscope, and later with the RetCam photographic device. The ROP stages were evaluated according to the ICROP classification. All eyes were treated with cryo-retinopexy at the threshold stage of ROP, followed by intraocular surgery for progression of traction retinal detachment. The surgical technique was a 3-port 25-G PPV (pars-plicata vitrectomy) with insertion of ports 1.5 mm from limbus. The PPV was performed using the Constellation (ALCON) operating unit, controlling the intraocular pressure for 15 torr. The assessment of visual acuity was performed according to the scale: no light perception (no response of the child to light), light sensitivity (positive or negative reaction to illumination), fixation of light. RESULTS: The retina stayed attached in all operated eyes, more in each case-report. CONCLUSION: Contemporary vitreoretinal surgery allows for the anatomical success of traction retinal detachment surgery during ROP already in neonatal age.Key words: retinal detachment, retinopathy of prematurity, PPV, surgery.

[Cesarean section incidence and vaginal birth success rate at term pregnancy after myomectomy]. / Incidence císarského rezu a úspesnost vaginálne vedeného porodu u tehotných po myomektomii.

OBJECTIVE: To compare the incidence of primary and acute cesarean section (CS) and to compare success rate of vaginal delivery. To determine the frequency of maternal complications and evaluation of post-partum condition of the newborn. STUDY DESIGN: Prospective, pilot, cohort study. SETTING: Department of Gynecology and Obstetrics Masaryk University and University Hospital Brno. METHODS: Analysis of patients with physiologically ongoing singleton pregnancy and term delivery, vertex presentation. Women from the study group (n = 67) underwent myomectomy because of symptomatic, solitary uterine fibroid. Women from the control group (n = 4079) had no history of myomectomy. Analysis was aimed at comparing the incidence of primary and acute CS and comparing success rate of vaginal delivery in both groups and determing the frequency of maternal complications and evaluation of post-partum condition of the newborn. RESULTS: A significantly higher incidence of primary cesarean section was observed in the study group with a history of myomectomy compared to the control group (n = 20, 29.9%; versus n = 396, 9.7 %, p < 0.001). No statistically significant difference in the incidence of acute cesarean section in both groups was recorded (n = 7, 10.4%; versus n = 570, 14.0%, p = 0.079). No statistically significant difference in the success of vaginal delivery in both groups was recorded (n = 40, 85.1%; versus n = 3113, 84.5%, p = 0.079). The excessive blood loss was the most frequent complication in both group (n = 9, 13.4%; versus n = 214, 5.2%, p = 0.057). No statistically significant difference in the incidence of uterine rupture and postpartum hysterectomy was recorded. No maternal or fetal death related to childbirth was observed. CONCLUSION: The history of myomectomy does not increase the incidence of acute cesarean section in the group of strictly selected patients suitable for vaginal birth and has no impact on the success of vaginal delivery. Careful management of labor is a prerequisite for a low risk of maternal complications and good perinatal outcomes.

[Histological types of uterine fibroids in reproductive age and postmenopausal women]. / Histologické typy delozních myomu u pacientek v reprodukcním veku a postmenopauze.

OBJECTIVE: To review the incidence of histologic variants of uterine fibroids of patients in reproductive age and postmenopause. Analysis of potential relations between histological fibroids variants and hormonal activity of the patient. DESIGN: Retrospective analysis. SETTING: Department of Obstetrics and Gynecology, Masaryk University and University Hospital Brno. MATERIAL AND METHODS: Retrospective analysis of 2,397 women who underwent myomectomy or hysterectomy at the Department of Obstetrics and Gynecology, Masaryk University and University Hospital Brno in years 2008-2014. According to input criteria - age of patients between 18-65 years, ultrasound confirmed uterine fibroid. Exclusion criteria was irregular menstrual cycle, hormonal therapy in history or hysterectomy performed for tumors of the small pelvis or for cancer of the uterus or cervix.Group A consisted of 235 patients with regular menstrual cycles, between ages 18-40. Myomectomy was chosen for these patients.Group B consisted of 433 postmenopausal patients between ages 50-65. Laparoscopic and abdominal hysterectomy was performed to these patients. RESULTS: A statistically significant difference was observed in the occurrence of epithelioid type of leiomyoma between women age groups 18-40 and 50-65. In the group of postmenopausal women four malignant forms of leiomyoma were recorded, which were not statistically relevant. CONCLUSION: After evaluating statistical analysis it was found, that there is a statistically significant difference in epithelioid type of uterine leiomyoma. Four patients were detected malignant variant of leiomyoma - leiomyosarcoma in the group of postmenopausal women.

[Postoperative results of hydrophilic expandable intraocular lenses ACQUA (Mediphacos) implantation]. / Pooperacní výsledky expandibilní nitroocní cocky ACQUA (Mediphacos).

PURPOSE: To assess postoperative outcomes of implanted hydrophilic expandable intraocular lenses ACQUA. MATERIAL AND METHODS: One hundred eyes of 75 patients with implanted intraocular lens (IOL) ACQUA were involved. IOLs were implanted during the period 2004 to 2005. The uncorrected visual acuity (UCVA) and the best-corrected visual acuity (BCVA), refractive error and its spherical equivalent (SE) were measured preoperatively and 1 day, 1, 6, 12 months postoperatively. Possible postoperative complications were evaluated as well. The patients were divided into two groups: first group with the age-related macular degeneration (ARMD) and the second one without it. RESULTS: Sixty-five patients (90 eyes) finished the one-year follow-up period. Preoperative UCVA was 0.23 +/- 0.19, BCVA 0.43 +/- 0.23 and SE + 0.15 +/- + 2.06 D (dioptres). Statistically significant differences between UCVA and BCVA one day and one month postoperatively were established. Six months after the operation and later on, the mean UCVA and BCVA were 0.61 +/- 0.26, and 0.82 +/- 0.23 respectively in all eyes, and 0.67 +/- 0.24, and 0.9 +/- 0.17 respectively in the group of eyes without ARMD. Spherical equivalent was stable during the whole follow-up period, one year after the surgery it was -0.1 +/- 1.12 D in the group of all 90 eyes. The IOL central positioning in the bag was excellent in 86 eyes. Nd:YAG laser anterior capsulotomies were performed in two eyes due to the stricture of the anterior capsule and posterior capsulotomy was performed in one eye due to the fibrous secondary cataract. The ACQUA IOL had to be explanted from one eye because of recurrent acute non-infectious inflammation of the anterior segment. CONCLUSION: According to our experience, the IOL ACQUA Mediphacos shows good and stable postoperative outcomes.

Mutation analysis of candidate genes SCN1B, KCND3 and ANK2 in patients with clinical diagnosis of long QT syndrome.

The long QT syndrome (LQTS) is a monogenic disorder characterized by prolongation of the QT interval on electrocardiogram and syncope or sudden death caused by polymorphic ventricular tachycardia (torsades de pointes). In general, mutations in cardiac ion channel genes (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2) have been identified as a cause for LQTS. About 50-60 % of LQTS patients have an identifiable LQTS causing mutation in one of mentioned genes. In a group of 12 LQTS patients with no identified mutations in these genes we have tested a hypothesis that other candidate genes could be involved in LQTS pathophysiology. SCN1B and KCND3 genes encode ion channel proteins, ANK2 gene encodes cytoskeletal protein interacting with ion channels. To screen coding regions of genes SCN1B, KCND3, and 10 exons of ANK2 following methods were used: PCR, SSCP, and DNA sequencing. Five polymorphisms were found in screened candidate genes, 2 polymorphisms in KCND3 and 3 in SCN1B. None of found polymorphisms has coding effect nor is located close to splice sites or has any similarity to known splicing enhancer motifs. Polymorphism G246T in SCN1B is a novel one. No mutation directly causing LQTS was found. Molecular mechanism of LQTS genesis in these patients remains unclear.

[Comparison of posterior capsule opacification in 2 types of implanted artificial intraocular lens]. / Porovnání opacit zadního pouzdra u dvou typu implantovaných umelých nitroocních cocek.

PURPOSE: To compare posterior capsule opacification (PCO) incidence and the best corrected visual acuity (BCVA) in patients who had the soft intraocular lens (IOL) made of hydrophobic acrylic material (AcrySof MA30BA, MA60BM) implanted in their one eye and IOL made of silicone material (Allergan SI-30NB) implanted in their second eye. All patients included in this study were operated on at Department of Ophthalmology, University Hospital, Hradec Králové, Czech Republic during the period from 1999 to 2002. METHODS: Twenty-four patients (8 males, 21 females) were included in this study; they were 3 to 6 years after surgery (median 5 years). The EPCO 2000 software (The Evaluation of Posterior Capsule Opacification) was used for PCO assessment. Eyes treated with Nd: YAG laser capsulotomy were excluded from EPCO 2000 evaluation. The density of the opacification was graded clinically from 1 to 4. We compared BCVA, PCO index for every PCO grade and total PCO index. RESULTS: Seven eyes of five patients required Nd: YAG laser capsulotomy, 2 eyes with AcrySof IOL, 5 eyes with Allergan IOL. Median of total PCO index for 48 eyes of 24 patients was for AcrySof IOL 0.496 vs. 0.315 for Allergan IOL. On the evaluation, median of BCVA was for AcrySof IOL 1.0 vs. 0.67 for Allergan IOL. CONCLUSIONS: The difference in PCO incidence and BCVA between the silicone and the soft acrylic IOLs were not conclusive in this study. But Nd: YAG laser capsulotomy incidence was higher in the silicone IOLs.

[Extension of QT interval as a consequence of risk factor accumulation--case study]. / Prodlouzení QT intervalu jako dusledek kumulace rizikových faktoru: kazuistika.

BACKGROUND: Many non-cardiovascular drugs have a potential for QT interval prolongation. This phenomenon can be related to occurence of ventricular tachycardia torsades de pointes, syncopi and even sudden death. DESCRIPTION OF THE CASE: A female patient treated with antracycline cytostatics developed a depression of left ventricle ejection fraction. At the same time she was administered 2 common drugs with proarrhythmic potential--terfenadine and itraconazole. In this patient hypokalemia also occured. Combination of the above mentioned risk factors led to QT interval prolongation and frequent ventricular tachycardias torsades de pointes degenerating in ventricular fibrillations with need of repeated defibrillations. Both drugs were withdrawn and dysiontaemia corrected. Then arrhythmias disappeared and QT interval completely normalized. In this patient the congenital long QT syndrome was not proved. DISCUSSION AND CONCLUSIONS: In proarrhythmic effect of non-cardiovascular drugs the following factors play role: predisposition of a particular individual, "repolarization reserve", interindividual differences in drug metabolism. The risk factors are age, sex, dysiontaemia, heart disease and drug interactions. By different choice of medication and attention to risk factors teh life threat to the described patient could have been avoided.

[Mutational analysis of LQT genes in individuals with drug induced QT interval prolongation]. / Mutacní analáza LQT genu u jedincu s polékovým prodlouzením QT intervalu.

BACKGROUND: In a long list of non-cardiovascular drugs a risk of QT interval prolongation and thus an increased risk of malignant arrhythmias has been described. The precise mechanism remains unclear. Many of these drugs are potent blockers of cardiac ion channels. Thus, prolongation of repolarization could be caused by latent ion channel genes mutations which are revealed under stress conditions. GROUP OF PATIENTS AND METHODS: Patients were recruited in screening of antipsychotic drugs with proarrhythmic potential, another sporadic cases were reffered from regional hospitals. In 13 individuals pathologic values of corrected QT interval (> 0.44 s in males, > 0.46 s in females) were observed. Eleven patients gave their consent to mutational analysis of KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2 and KCNJ2 genes (associated with congenital long QT syndrome). RESULTS: At present complete results of mutational analysis are available in 8 patients. In 5 individuals changes in DNA sequence were found which are considered normal variants according to the literature (nucleotide and aminoacid polymorphisms, intronic variants). In 1 male a KCNQ1 gene mutation A590T was identified (yet not reported in literature). CONCLUSION: Mechanisms of drug-induced QT interval prolongation is complex and it cannot be explained simply by ion channel disorders.

[Vernal keratoconjunctivitis and possibilities its treatment]. / Vernální keratokonjunktivitida a moznosti její lécby Kazuistika.

The authors present a case of vernal keratoconjunctivitis (VKC) in 5 years old boy. Despite intensive topical pharmacological therapy (mast-cell stabilizers, antihistamines, steroids in acute exacerbations) unsatisfied reduction of the symptoms was observed and cornea became involved in the left eye (LE). Repeated surgical abrasion of the papillary hypertrophy was performed with temporaly relief. We decided to provide a cryocoagulation of the papillary hypertrophy in the LE. We did not see any pre and post operative complications, significant improvement was observed and the patient is now (13 months after the surgery) in a good condition, on mast cell stabilizers only.

[Results of cataract surgery in patients aged 80 years and older]. / Výsledky operace katarakty u pacientu starsích 80 let.

BACKGROUND: The authors evaluate the benefits of the cataract surgery in old patients. METHODS AND RESULTS: Best corrected visual acuity (BCVA) before operation, on the first postoperative day and 6 months after surgery were assessed as well as changes in the quality of life using the modified test VF-8. The positive effect of the cataract surgery was proved in patients in this age group. Not only recovery of the visual functions, but also improvement of the orientation and of the quality of life was reported by those patients. CONCLUSIONS: Based on our results we consider the cataract surgery indicated for old patients even with systemic morbidities.

[Spontaneous late subluxation of capsule, intraocular lens and capsular ring in patient with pseudoexfoliation syndrome--a case report]. / Spontánní pozdní subluxace pouzdra, nitroocní cocky a kapsulárního prstence u pacientky s pseudoexfoliacním syndromem--kazuistika.

The authors present a case of spontaneous late subluxation of capsule, intraocular lens and capsular ring in patient with pseudoexfoliation syndrome. A 78-year old woman was operated (phacoemulsification, implantation of capsular tension ring and intraocular lens) in the left eye in June 2001 and the same procedure was performed in the right eye in September 2001. No early postoperative complicantions were encountered. The patient was referred with vision reduction in the left eye in May 2004. Biomicroscopy revealed inferior dislocation of the capsular bag, capsular ring, and intraocular lens. Explantation of the whole complex and secondary anterior chamber lens was provided. The postoperative course was uneventful, and visual functions improved.

[The role of ergometric testing in diagnosis of latent long QT syndrome]. / Postavení ergometrického vysetrení v diagnostice latentního syndromu dlouhého QT intervalu.

BACKGROUND: The long QT syndrome is a genetically determined disease based on mutations of ion membrane channel genes. The resulting prolongation of repolarization increases a risk of malignant ventricular arrhythmias and sudden death. The diagnosis is problematic in individuals with borderline or even normal corrected QT interval value. Ventricular arrhythmias in this syndrome are often provoked by exercise, therefore exercise testing is considered as a useful differential diagnostic method. METHODS: In a 24-member family an occurrence of the long QT syndrome was established clinically in 7 patients. In other 3 members borderline corrected QT interval values were found (0.44-0.46 s). In these individuals a stress testing by bicycle ergometry was performed. RESULTS: During exercise in a 28-year old man (patient III/6) the corrected QT interval prolonged to 0.53 s, in a 27-year old man (patient III/2) and in a 20-year old woman (patient III/9) physiological QT interval shortenings were observed (0.4 s during peak exercise). The diagnosis was confirmed by molecular genetic investigation. In patient III/6 (along with other symptomatic family members) a mutation in exon 7 of KCNQ1 (previously called KVLQT1) gene was found. In patients III/2 and III/9 no signs of KCNQ1 gene pathology were present. CONCLUSIONS: In families with clinically established diagnosis of long QT syndrome occurrence the exercise testing reveals previously asymptomatic individuals, at least in LQT1 type (which is the most common). In general stress testing and measurement of QT interval dynamics is a necessary part of arrhythmological investigation especially in young individuals with history of syncope.