DNA repair gene XPD Asp312Asn and XRCC4 G-1394T polymorphisms and the risk of autism spectrum disorder.

Autism spectrum disorder (ASD) is a complex disorder, and its extreme heterogeneity further complicates our understanding of its biology. Epidemiological evidence from family and twin studies supports a strong genetic component in ASD etiology. Oxidative stress and abnormal DNA methylation have been implicated in the pathophysiology of ASD. Brain tissues from ASD cases showed higher levels of oxidative stress biomarkers than healthy controls in postmortem analysis. Association between oxidative stress and DNA damage has been well-known. Thus, we sought to investigate a potential link between DNA repair genes and ASD and analyze the role of XPD Asp312Asn and XRCC4 G-1394T gene polymorphisms for ASD in the Turkish population. Genotyping was conducted by PCR-RFLP based on 100 patients and 96 unrelated healthy controls. We, for the first time, demonstrated a positive association between XRCC4 gene variants and ASD risk. Frequencies of XRCC4-1394 T/G+G/G genotypes were higher in patients (%34) than the controls (%18.7). The statistical analysis revealed that the individuals who had XRCC4-1394 T/G+G/G genotype had an increased risk for ASD (OR = 2.23, 95% CI = 1.10-4.55). However, no significant association was found for XPD Asp312Asn polymorphism with the risk of ASD. Our findings suggest that XRCC4 G-1394T polymorphism might be associated with ASD pathogenesis.

DETECTING PORCN MICRODELETIONS IN A LARGE FAMILY WITH FOCAL DERMAL HYPOPLASIA.

Focal dermal hypoplasia (FDH), an X-linked dominant disease with a highly variable phenotype, presents mainly with congenital linear pigmentation of the skin, herniation of fat through the dermal defects and multiple papillomas. PORCNmicrodeletions are identified in a total of 12 FDH patients to date. Routine molecular methods for detecting microdeletions have proven not to be effective, as patients also carry a normal allele. Additionally, methods using copy number estimations are labor-intensive, time-consuming and require expensive equipment. With respect to the molecular diagnosis of FDH, we aimed to investigate the inheritance of maternal disease allele in a three-generation FDH pedigree with seven affected members by using a simple yet efficient method. The strategy used in this study appeared to have the benefit of detecting all PORCN micro-deletions identified for FDH so far. The family with the largest number of related patients reported to date presented an opportunity to evaluate clinical variability, which was high, with the least affected and the most severely affected patients being half-sisters. The extensive intra-familial phenotypic variability observed in this FDH family suggests that genetic counselling should be part of management of this syndrome even in a family with a very mild case. The unique finding of IgA deficiency in the most severe case indicated that the feature could be a new characteristic of FDH.

Predictors of sexual function during pregnancy.

The aim of the study was to evaluate sexual functions of pregnant women and to determine the factors affecting their sexual function. The cross-sectional study recruited 286 pregnant women from a hospital. To collect data, 'Patient Information Form', 'State Anxiety Inventory' and 'Female Sexual Function Index' were used. The mean age of women was 29.15 ± 4.85 and 77.6% of them presented with sexual dysfunction. Having partner at advanced age, a history of miscarriage, a history of health problem during previous pregnancy and a high level of anxiety were found to be factors negatively affecting sexual function. Health professionals should be aware of a number of risk factors that may contribute to sexual dysfunction in pregnant women.

Giant hemorrhagic adrenal pseudocyst in a primiparous pregnancy: report of a case.

Adrenal cysts are rare and are usually discovered incidentally during diagnostic imaging, surgery, or autopsy. Most cystic lesions of the adrenal gland are nonfunctioning and become symptomatic when complicated by rupture, hemorrhage, or infection. A 40-year-old woman presented with a history of gradual-onset pain in her left flank region at 20 weeks' gestation. Ultrasound showed a 20-cm cystic mass in her left abdominal cavity. Pertinent laboratory tests were within normal limits. The patient underwent exploratory laparotomy, which revealed a 20 × 15-cm left adrenal cyst; thus, we performed left adrenalectomy with complete excision of the cyst. Histological examination confirmed a hemorrhagic adrenal pseudocyst. The patient had an uneventful postoperative course, and subsequent routine obstetric ultrasound examinations showed normal fetal activity and development until the pregnancy terminated with a stillbirth caused by pre-eclampsia at 34 weeks' gestation. To the best of our knowledge, this is only the 12th reported case of adrenal pseudocyst discovered during pregnancy. We analyze the clinicopathologic findings and discuss the possible association of pregnancy, with special reference to etiopathogenesis, presentation, diagnosis, and treatment.

A new syndrome presenting with dysmorphic facies, oculocutaneous albinism, glaucoma, cryptorchidism and mental retardation.

We report a case with a new syndrome that presents with glaucoma, cryptorchidism, oculocutaneous albinism, ataxia, hypotonia, autistic behaviour besides various major and minor craniofacial dysmorphic, skeletal, and neuroimaging findings, and suggest that this case represents a new syndrome not reported previously.

Sudden vision loss in a mucopolysaccharidosis I patient receiving enzyme replacement therapy.

A 25-year-old female was referred for short stature and joint deformities. Except for previous corneal transplantation, her medical history was unremarkable. Initial physical examination revealed the presence of a coarse facies, short neck, kyphosis, restricted joint movements and deformities, and cardiac murmur besides a normal intellect. Urine glycosaminoglycan levels were high, and blood enzyme assay indicated significantly low alpha-L-iduronidase levels. Mucopolysaccharidosis I (MPS I) was diagnosed and prompted the onset of enzyme replacement therapy (ERT), which significantly improved articular complaints, while cardiac pathology remained stable. At the eighteenth month of ERT, sudden vision loss developed. She spontaneously recovered her vision in a month. MPS I is a progressive disease, in which tissue accummulation of heparan and dermatan sulphate result from defective activity or lack of alpha-L-iduronidase. ERT in MPS I usually presents favourable outcomes or at least stabilization of symptoms. This present case qualifies as the first report ofa MPS I patient developing sudden vision loss under ERT. We suggest that further research studies are warranted for defining the efficiency and possible limitations of ERT.

Effectiveness of prolotherapy in the treatment of chronic rotator cuff lesions.

BACKGROUND: Rotator cuff lesions are one of the major causes of shoulder pain and dysfunction. Numerous non-surgical treatment modalities have been described for chronic rotator cuff lesions, but the debate continues over the optimal procedure. The aim of this report is to present the results of prolotherapy in the treatment of chronic refractory rotator cuff lesions. HYPOTHESIS: Dextrose prolotherapy will reduce pain and improve shoulder function and patient satisfaction. MATERIAL AND METHODS: We recruited 120 patients with chronic rotator cuff lesions and symptoms that persisted for longer than 6 months. Patients were divided into two groups: one treated with exercise (control group; n=60) and the other treated with prolotherapy injection (prolotherapy group; n=60). In the latter, ultrasound-guided prolotherapy injections were applied under aseptic conditions. In the former, patients received a physiotherapy protocol three sessions weekly for 12 weeks. Both groups were instructed to carry out a home exercise program. Clinical assessment of shoulder function was performed using a visual analog scale (VAS) for pain, Shoulder Pain and Disability Index (SPADI), Western Ontario Rotatory Cuff (WORC) Index, patient satisfaction, and shoulder range of motion. Patients were examined at baseline, weeks 3, 6, and 12, and last follow-up (minimum of one year). RESULTS: A total of 101 patients (44 controls and 57 in the prolotherapy group) completed all study protocols and were included in the study. Using a within-group comparison, both groups achieved significant improvements over baseline, as measured by the VAS, SPADI, WORC index, and shoulder range of motion (P<0.001). Using a between-group comparison, a significant difference was found in the VAS scores at baseline, weeks 3, 6, and 12, and last follow-up. In addition, significant differences were found in the SPADIs and WORC indices at weeks 6 and 12 and the last follow-up. Significant differences were found in shoulder abduction and flexion at week 12 and last follow-up, and in internal rotation at last follow-up. However, no significant was found in external rotation at any follow-up period. In the prolotherapy group, 53 patients (92.9%) reported excellent or good outcomes; in the control group, 25 patients (56.8%) reported excellent or good outcomes. CONCLUSION: Prolotherapy is an easily applicable and satisfying auxiliary method in the treatment of chronic rotatory cuff lesions. STUDY TYPE: Randomized prospective comparative trial. LEVEL OF EVIDENCE: Level of evidence 1.

Components of genetic counsellor education: A systematic review of the peer-reviewed literature.

The need for appropriately trained genetic counsellors to support genetic healthcare is now acknowledged. However, while programmes for education of genetic counsellors exist in a number of countries, these do not conform to any specific international standards. As genetic techniques, educational standards and professional standards have been evolved, and with increasing mobility of genetic counsellors, it is of great importance to have some comparison of education and training between different countries. This systematic review was conducted to determine the components of educational programmes for genetic counsellors worldwide that have been published in peer-reviewed literature. Databases were searched for studies published in English from 2000 to 2014 related to the topic. We identified 406 potential papers, of these, 11 studies met the inclusion criteria. The findings indicate that, in most cases, the theoretical components of genetic counsellor programmes conform to the recommendations and requirements of relevant professional bodies. However, clinical preparation of genetic counsellors in real-life professional practice settings seems to be less well addressed as this is essential to ensure genetic counsellors are able to provide safe patient care after graduation. Further work to gain agreement internationally on genetic counsellor education is needed.

On-line set-up corrections during radiotherapy of patients with gynecologic tumors.

PURPOSE: Positioning of patients with gynecologic tumors for radiotherapy has proven to be relatively inaccurate. To improve the accuracy and reduce the margins from clinical target volume (CTV) to planning target volume (PTV), on-line set-up corrections were investigated. METHODS AND MATERIALS: Anterior-posterior portal images of 14 patients were acquired using the first six monitor units (MU) of each irradiation fraction. The set-up deviation was established by matching three user-defined landmarks in portal and simulator image. If the two-dimensional deviation exceeded 4 mm, the table position was corrected. A second portal image was acquired using 30 MU of the remaining dose. This image was analyzed off-line using a semiautomatic contour match to obtain the final set-up accuracy. To verify the landmark match accuracy, the contour match was retrospectively performed on the six MU images as well. RESULTS: The standard deviation (SD) of the distribution of systematic set-up deviations after correction was < 1 mm in left-right and cranio-caudal directions. The average random deviation was < 2 mm in these directions (1 SD). Before correction, all standard deviations were 2 to 3 mm. The landmark match procedure was sufficiently accurate and added on average 3 min to the treatment time. The application of on-line corrections justifies a CTV-to-PTV margin reduction to about 5 mm. CONCLUSIONS: On-line set-up corrections significantly improve the positioning accuracy. The procedure increases treatment time but might be used effectively in combination with off-line corrections.

Reduction of irradiated small bowel volume and accurate patient positioning by use of a bellyboard device in pelvic radiotherapy of gynecological cancer patients.

PURPOSE: To reduce the volume of small bowel within pelvic treatment fields for gynecological cancer using a bellyboard device and to determine the accuracy of the prone treatment position. MATERIALS AND METHODS: Fifteen consecutive patients with a gynecologic malignancy who were treated with postoperative pelvic radiotherapy were selected for this study. The volume of small bowel within the treatment fields was calculated for both the supine and prone treatment positions. The patients were treated in the prone position in a so-called bellyboard device. During treatment sessions electronic portal images were obtained. An off-line setup verification and correction protocol was used and the setup accuracy of the positioning in the bellyboard was determined. RESULTS: The average volume of small bowel within the treatment fields was 229 cm(3) and 66 cm(3) in the supine and prone treatment, respectively, which means an average volume reduction in the prone position of 64% (95% CI 56-72%), as compared with the supine position. For the position of the patient in the field, the systematic error defined by the standard deviation (SD) of the mean difference per patient between simulation and treatment images was 1.7 mm in the lateral direction, 2.1 mm in the craniocaudal direction and 1.7 mm in the ventrodorsal direction. On average, only 0.4 setup correction per patient was required to achieve this accuracy. The random day-to-day variations were 1.9 (1SD), 2.6 and 2.3 mm, respectively. Standard deviations of the systematic differences between patient positioning relative to the bellyboard were 6.2 mm in lateral direction and 9.1 mm in craniocaudal direction. CONCLUSIONS: Treatment of gynecological cancer patients in the prone position using a bellyboard reduces the volume of irradiated small bowel. An off-line verification and correction protocol ensures accurate patient positioning. Daily setup variations using the bellyboard were small (1 SD<3 mm). Therefore for pelvic radiotherapy in patients with a gynecological malignancy, the use of a bellyboard is recommended.

Definition and validation of a reference target volume in early stage node-positive cervical carcinoma, based on lymphangiograms and CT-scans.

PURPOSE: To establish a reference planning target volume for postoperative radiotherapy in stage Ib and IIa N+ cervical carcinoma, based on 47 lymphangiograms and 15 CT-scans. METHODS: Radiation oncologists (n=17) from all radiotherapy institutes in The Netherlands were asked to define the clinical target volume (CTV) and planning target volume (PTV), and to delineate (on simulation films) the radiotherapy treatment portals following a radical hysterectomy with lymph node dissection for an early stage cervical carcinoma with positive iliac lymph nodes. A reference PTV was defined by using 47 normal lymphangiograms and CT-data of the pelvis from 15 patients who underwent surgery for cervical carcinoma. The simulation films were digitized and evaluated for adequacy in covering the PTV, previously individually determined by the radiation oncologists. Subsequently, the simulation films were also evaluated for adequacy in covering the reference PTV. RESULTS: Large variations were observed in the portals used and in treatment techniques. From the digitized films, it appeared that in 50% of the cases the defined PTV was not covered adequately. Furthermore, 71% of the treatment plans would not cover the lateral borders of the reference PTV sufficiently. CONCLUSIONS: There appears to be no consensus on the target volumes to be irradiated in postoperative radiotherapy of early stage cervical carcinoma. When a PTV defined on the basis of lymphangiograms and CT-data is taken as a reference, 71% of the treatment plans would not cover this PTV adequately. These findings indicate the need for a consensus in the design of standardized treatment volumes.

Anophthalmia-Waardenburg syndrome: a report of three cases.

We report on 2 Turkish families with children who had bilateral anophthalmia, upper and lower limb abnormalities, mental retardation and consanguineous parents. We have evaluated the 2 cases in the first family and the only case in the second as anophthalmia-Waardenburg syndrome. This is an extremely rare autosomal recessive syndrome.

Changes in the antioxidant system in epileptic children receiving antiepileptic drugs: two-year prospective studies.

The aim of this study was to measure changes in the antioxidant systems of epileptic children who had been receiving either valproate or carbamazepine monotherapy for 2 years. For this purpose, levels of erythrocyte glutathione, glutathione peroxidase, superoxide dismutase, and serum lipid peroxidation in 25 healthy children and 27 children who had previously been diagnosed as having epilepsy but who had not, prior to the study, received antiepileptic drugs were tested. Of the 27 epileptic children, 14 were given valproate, and the remaining 13 were given carbamazepine; these tests were repeated in the 13th and 24th months of treatment. The results showed that, during valproate therapy, the lipid peroxidation levels of the epileptic children increased and the glutathione peroxidase levels decreased in comparison with those levels recorded in the control and pretreatment groups. In addition, the superoxide dismutase levels were found to be increased during the first year of valproate therapy when compared with those of the pretreatment group. However, during carbamazepine therapy, lipid peroxidation levels increased when compared with the control group only, not the pretreatment group. Furthermore, the results showed that during the second year of treatment, the superoxide dismutase levels of the children receiving carbamazapine monotherapy were found to be higher than those of both the control and pretreatment groups. From these results, it can be concluded that the antioxidant systems of the children who had been receiving valproate therapy during the 2 years were more significantly affected than those of the children who had been receiving carbamazepine.

N-acetyl-beta-glucosaminidase and beta-galactosidase activity in children receiving antiepileptic drugs.

To evaluate renal tubular function in children receiving antiepileptic drugs the urinary activity of two lysosomal enzymes, N-acetyl-beta-glucosaminidase and beta-galactosidase, were measured. The enzyme levels were determined before the administration of antiepileptic drugs and 8 months after. Fourteen epileptic children received valproate, and 17 received carbamazepine. The urinary activity of these enzymes in 25 healthy control patients also was examined. Increased N-acetyl-beta-glucosaminidase activity was found in 50% of patients taking valproate and in 17.6% of patients taking carbamazepine. Increased beta-galactosidase activity was found in 28.5% of patients taking valproate and 11.7% of patients taking carbamazepine compared with the results before treatment. On the basis of these results, it is suggested that patients taking antiepileptic drugs, especially valproate, may demonstrate minor signs of tubular dysfunction. In those patients who use these drugs at increased dosage levels or for long periods, the possibility of tubular dysfunction may be increased, and these dysfunctions may manifest in clinical symptoms.

Neuroimaging findings of four patients with Sandhoff disease.

Sandhoff disease is a severe form of GM2 gangliosidosis that is caused by the deficiency of both hexosaminidase A and B. Startle reaction, hypotonia, psychomotor retardation, and blindness are the main clinical features. Presented are computed tomography and magnetic resonance imaging findings of four patients with Sandhoff disease diagnosed by enzymatic analyses. Bilateral homogeneous thalamic hyperdensity was evident on computed tomography. Magnetic resonance imaging scans revealed mild cortical atrophy, a thin corpus callosum, and abnormal signal intensities in the caudate nucleus, globus pallidum, putamen, cerebellum, and brainstem. No correlation was evident between the severity of the central nervous system imaging findings and the clinical pictures. In this article the neuroimaging findings of four patients with Sandhoff disease are discussed.

Dysmorphic face in two siblings with infantile neuroaxonal dystrophy.

Infantile neuroaxonal dystrophy (INAD) is an autosomal recessive, neurodegenerative disease with onset in the first or second year of life. It has been reported that INAD shows numerous phenotype characteristics including problems associated with vision, hearing and physical coordination. It has however been very rare to see facial dysmorphism in these children. The study analyzes a girl and boy of a first cousin marriage with infantile neuroaxonal dystrophy affected at birth. At infancy, the children were examined in the Cerrahpasa Medical Faculty Genetic Research Center, Istanbul. They had typical INAD features such as the lack of head control, vision, speech, sitting, and walking which are also seen in children with other congenital abnormalities. These children showed remarkable dysmorphism in the face which included prominent forehead, strabismus, small nose, fish mouth (boy), micrognathia, and large and low-settled ears. The presence of these facial features makes the patients appear unique and diagnosis more accurate. While these features are commonly seen diagnosis may be difficult at its onset. Until now this appearence has not been reported in INAD patients. In conclusion, in the first few months of life without any clinical or neurological signs, the physician should also consider diagnosing the disease of the infant as INAD.

Antioxidant system in Down syndrome: a possible role in cataractogenesis.

Recent studies show a relationship between oxidants, antioxidants, and degenerative disease of aging like cataract formation. Focal lens cortical changes and cortical liquification have been reported in patients with Down syndrome (DS) over 14 years. There is evidence supporting the hypothesis that trisomy 21 patients have an increase in free radical reactions. These changes in antioxidant system may play a role in cataractogenesis in Down syndrome. We screened serum samples from 12 patients with DS and cataract: and 12 healthy age and sex-matched persons. We evaluated the antioxidant enzyme activities of superoxide dismutase (SOD), glutathione peroxidase (GSHPx), glutathione-S-transferase (GST) and reduced glutathione (GSH) in erythrocytes. SOD and GSHPx levels of patients with DS were significantly higher than the control group. No significant changes were observed in GST and GSH levels between the DS and control groups. These findings suggest impairment in antioxidant system, which may be a possible mechanism for early cataract formation in DS.

A case of acampomelic campomelic dysplasia.

Acampomelic campomelic dysplasia is a rare variant of campomelic dysplasia syndrome affecting bone and connecting tissue. This syndrome is implicated by the absence of bowed limbs. Affected children have a characteristically smooth facial profile and are born with respiratory distress. A 15 day old Turkish boy presented with a small flat face, dolicocephalic head, proptotic eyes, short neck, low-set ears and a small thoracic cage. Limbs were mesomelically short and bilateral talipes equinovarus was present. The radiological findings indicated hypoplastic scapulae, narrow ribs, small thorax, thin claviculaes, and small iliac wings. Angulation of the femur, tibia and humerus was not observed. Our case, suited to acampomelic campomelic dysplasia, is discussed with differential diagnosis and compared with previously reported cases of the syndrome.

A case of symbrachydactyly with oligodactyly.

The term symbrachydactyly describes syndactyly accompanied by brachydactyly. Brachydactyly is seen in middle phalanges of both hands and feet and very short in length or absent. As for syndactyly it is a cutaneous type. It has always been observed unilaterally and sporadically. A familial type of this syndrome has also been reported. There have been many classifications of symbrachydactyly. Of these, Blauth classification is the most favored one. Yet these classifications have been inadequate to include many recently discovered other forms of symbrachydactyly. A three month old child was brought to the Istanbul University Genetic Research Center because of his abnormal hands and feet. He was the second child of a couple who had no kinship ties to each other. In the history of the family, there was no mention of any anomaly as such. There was a complete syndactyly involving the 3rd through the 5th fingers, partial syndactyly between the 2nd and 3rd, and the thumb was normal in the right hand. There was only one finger in the left hand. There was total syndactyly in four toes of the right foot with oligodactyly and absence of the big toe. The left foot had five toes with a complete syndactyly between the 2nd and the 3rd. Radiological observation indicated that the middle phalanges of both extremities were rudimentary or never developed. There was no osseous syndactyly. As observed in this case, oligodactylous type that is bilateral and involves both hands and feet together is very unusual. The purpose of this study is to present a rare case of this anomaly that requires a reassessment of symbrachydactyly and its traditional classifications.