Genetic Syndromes Research Articles

A comparative analysis of surgically excised hereditary and sporadic pheochromocytomas: Insights from a single-center experience.

Pheochromocytoma is a tumor that usually originating from adrenal medullary chromaffin cells and producing one or more catecholamines, can manifest as hereditary or sporadic. While the majority pheochromocytomas are sporadic, hereditary forms are often associated with genetic syndromes such as von Hippel-Lindau, multiple endocrine neoplasia type 2, and neurofibromatosis type 1. This study aims to analyze data from our series of surgically excited pheochromocytoma patients and compare the characteristics between hereditary and sporadic cases. We retrospectively evaluated 33 diagnosed pheochromocytoma patients, documenting clinical features, surgical complications, and tumor characteristics in both hereditary and sporadic cases. Among the patients, 21% (7 individuals) had hereditary pheochromocytoma, while 79% (26 individuals) had sporadic cases. During diagnosis, hereditary pheochromocytoma patients exhibited a significantly lower mean age compared to the sporadic group (26.4 ± 9.9 years vs. 50.4 ± 14.0 years; p < 0.001). The maximum tumor size was also lower in hereditary cases compared to sporadic cases (p = 0.004). Adrenal tumor localization analysis showed that 63.6% were right-sided, 24.2% were left-sided, and 12.1% were bilateral. Laboratory analysis revealed significantly higher urinary norepinephrine levels in hereditary pheochromocytoma patients (p = 0.021). Our findings suggest that hereditary pheochromocytoma cases are characterized by a younger age at diagnosis, smaller tumor size, and a higher prevalence of multiple bilateral adrenal adenomas. We recommend genetic testing for all pheochromocytoma patients, particularly those with early-onset disease and bilateral adrenal tumors.

Experiences in Tube Weaning Children with Congenital Heart Disease and Oral Feeding Aversion.

Infants and children with congenital heart disease (CHD) often require supplemental nutrition via tube feeding before and after surgery. Tube feeding may be required due to poor weight gain, inadequate oral-motor skills, and/or reduced endurance for oral feeding. Our team has described a successful approach to weaning this population (Horsley et al. (2022) Pediatr Cardiol 43:1429-1437). A subgroup of tube-fed patients with CHD who demonstrate oral feeding aversion (OA) presents unique challenges to the tube weaning process. We discuss our team's experience with tube weaning orally averse children with CHD. Of 36 patients enrolled in the Cincinnati Children's Heart Institute Cardiology Feeding Tube Wean Clinic, 11 (31%) were determined to have oral feeding aversion (OA) by a speech-language pathologist (SLP). Descriptive data comparing the OA group to the non-averse group was gathered prior to and during the wean. Both groups had the ability to tube wean successfully, although the OA group had lower median oral intake (9 vs 24%) and higher age at start of the wean (9 vs 4months). Those with OA also had a longer median duration of wean in days (17 vs 12days) and higher likelihood of return to tube feeds within six-month post-wean (22 vs 0%). Additionally, the OA group had a higher percentage of genetic syndromes (36 vs 16%), although this was not found to be statistically significant in this study. Children with OA present with unique challenges for tube weaning. The results of this study show that weaning children with CHD and OA is possible with a multidisciplinary team who is knowledgeable about this population.

Current approach to genetic testing and genetic evaluation referrals for adults with congenital heart disease

BackgroundCongenital heart disease (CHD) is the most common congenital anomaly. Up to 33% have an identifiable genetic etiology. Improved medical and surgical management of CHD has translated into longer life expectancy and a rapidly growing population of adults living with CHD. The adult CHD (ACHD) population did not have access during childhood to the genetic technologies available today and therefore have not had a robust genetic evaluation that is currently recommended for infants with CHD. Given this potential benefit; the aims of this study were to determine how ACHD cardiologists offer genetics services to patients and identify the indications that influence decision-making for genetics care.MethodsWe performed a descriptive cross-sectional study of ACHD cardiologists. A study-developed questionnaire was distributed via emailed REDCap link. The recruitment email was sent to 104 potential respondents. The survey was open from 06/2022 to 01/2023.ResultsThirty-five cardiologists participated in the study (response rate of 34%). Most cardiologists identified as white (77%) and male (66%). Cardiologists were more likely to refer patients to genetics (91%) than to order testing themselves (57%). Of the testing ordered, chromosomal testing (55%) was ordered more than gene sequencing (14%). Most cardiologists would refer a patient with a conotruncal lesion (interrupted aortic arch) over other indications for a genetics evaluation. There were more reported barriers to ordering genetic testing (66%) compared to referring to genetics for a genetics evaluation (23%). Cardiologists were more confident recognizing features suggestive of a genetic syndrome than ordering the correct test (p = 0.001). Regarding associations between clinical factors and current practices, more years in practice trended towards less referrals and testing. Evaluating a greater number of patients (p = 0.11) and greater confidence recognizing syndromic features (p = 0.12) and ordering the correct test (p = 0.09) were all associated with ordering more testing.ConclusionTesting for microdeletion syndromes is being offered and completed in the ACHD population, however testing for single-gene disorders associated with CHD is being under-utilized. Developing guidelines for genetic testing in adults with CHD could increase access to genetic services, impact medical management, reduce uncertainty regarding prognosis, and inform recurrence risk estimates.

Introduction: A Practical Guide to Central Nervous System Malformations—From Genetics, to Diagnosis and Treatment

AbstractCentral nervous system (CNS) malformations encompass diverse congenital anomalies impacting brain and spinal cord development, profoundly affecting neurological function. They arise from disruptions in embryonic neural tube formation, neuronal migration, and cortical organization. This abstract provides a comprehensive overview of CNS malformations, covering classification, etiology, clinical manifestations, and diagnostic challenges. CNS malformations fall into distinct groups: neural tube defects (e.g., anencephaly, spina bifida), resulting from incomplete neural tube closure; malformations of cortical development (e.g., lissencephaly, polymicrogyria), featuring irregularities in cortical folding; and anomalies affecting structures like the corpus callosum, cerebellum, and CNS vasculature, alongside conditions such as hydrocephalus and Chiari malformations. Genetic factors, including mutations in LIS1, DCX, and RELN, contribute significantly, while environmental factors like maternal folic acid deficiency also play a role. Some malformations occur in genetic syndromes (e.g., tuberous sclerosis, neurofibromatosis). Clinical presentations vary, with neural tube defects typically presenting severe deficits at birth, while cortical malformations manifest as intellectual disabilities, seizures, and motor deficits. Hydrocephalus elevates intracranial pressure, and Chiari malformations cause headaches and neurological symptoms. Diagnosis necessitates a multidisciplinary approach involving clinical evaluation, neuroimaging, genetic testing, and histopathological analysis. Prenatal diagnosis via ultrasound and magnetic resonance imaging is crucial for planning interventions, while postnatal diagnosis relies on clinical and imaging findings.Understanding CNS malformations is vital for early detection, intervention, and comprehensive care provision. Advances in genetics and neuroimaging offer hope for improved outcomes and better quality of life for affected individuals.

Magnetic-Resonance-Imaging-Guided Cryoablation for Solitary-Biopsy-Proven Renal Cell Carcinoma: A Tertiary Cancer Center Experience

Background: Our purpose is to evaluate the long-term oncologic efficacy and survival rates of MRI-guided cryoablation for patients with biopsy-proven cT1a renal cell carcinoma (RCC). Materials and Methods: We retrospectively reviewed our renal ablation database between January 2007 and June 2021 and only included patients with solitary-biopsy-proven cT1a RCC (≤4 cm) who underwent MRI-guided cryoablation. We excluded patients with genetic syndromes, bilateral RCC, recurrent RCC or benign lesions, those without pathologically proven RCC lesions and patients who underwent radiofrequency ablation or CT-guided cryoablation. For each patient, we collected the following: age, sex, lesion size, right- or left-sided, pathology, ablation zone tumor recurrence, development of new tumor in the kidney other than ablation zone, development of metastatic disease, patient alive or not, date and cause of death. We used the Kaplan and Meier product limit estimator to estimate the survival outcomes. Results: Twenty-nine patients (median age 70 years) met our inclusion criteria. Twenty-nine MRI-guided cryoablation procedures were performed for twenty-nine tumor lesions with a median size of 2.2 cm. A Clavien–Dindo grade III complication developed in one patient (3.4%). Clear cell RCC was the most reported histology (n = 19). The median follow up was 4.5 years. No tumor recurrence or metastatic disease developed in any of the patients. Two patients developed new renal lesions separate from the ablation zone. The 5- and 10-year OS were 72% and 55.6%, respectively. The 5- and 10-year DFS were 90.5% and the 5-year and 10-year LRFS, MFS and CSS were all 100%. Conclusions: MRI-guided cryoablation is a safe treatment with a low complication rate. Long-term follow-up data revealed long-standing oncologic control.

Redefine "benign": A misnomer in the context of patients with genetic skin tumour syndromes.

Redefine "benign": A misnomer in the context of patients with genetic skin tumour syndromes.

Genome-wide sequencing in children with epilepsy and developmental disorders

The progress of genetic diagnostic methods and a significant improvement in the quality of next-generation sequencing (NGS) have led to a revolution in the study of the genetics of epilepsy. Genome-wide sequencing (PSG) is the «gold standard» in genetic research in epilepsy.Material and methods. Genome-wide sequencing was performed in 168 probands aged from 1 month to 18 years with a suspected diagnosis of genetic epilepsy. PSG was prescribed to patients who, alongside with epilepsy, had delayed intellectual/speech development and/or motor disorders and behavioral disorders.Results. According to the results of PSG, genetic variants related to the phenotype of the disease were detected in 137 out of 168 (81.5%) children, variations in the number of DNA copies were noted in 14 out of 168 (8.3%) patients. Variants with unclear clinical significance were described in 35 of 137 (25.54%). In the remaining 102 out of 137 (74.45%) patients, the identified causative genetic variants were described as probably pathogenic and pathogenic. Monogenic developmental and epileptic encephalopathies (DEE) were detected in 37/137 or 27% of all patients, while the spectrum of these genetic encephalopathies was extremely wide (from DEE type 1 to DEE type 97). In 52/137 (37.9%) children, the presence of a specific genetic syndrome outside the framework of the DEE, classified in OMIM, was confirmed.Conclusion. The results confirm the high informative value of genome-wide sequencing in a group of children with a combination of epilepsy, intellectual, speech, motor and behavioral disorders. In most cases, the results allow either to prescribe a genotype-oriented symptomatic (less often pathogenetic) treatment, or rationally justify the tactics of further observation and examination, as well as to increase the effectiveness of medical and genetic counseling. The authors express their sincere gratitude to the Charity foundation for medical and social genetic aid projects «Life Genome” for assistance in conducting genome-wide sequencing of most of the described patients.

Centralization of care for rare genetic syndromes associated with cancer: improving outcomes and advancing research on VHL disease.

Von Hippel-Lindau (VHL) disease is a rare genetic syndrome caused by a germline pathogenic variant in one VHL allele. Any somatic event disrupting the other allele induces VHL protein (pVHL) loss of function, ultimately leading to patients developing multiple tumours in multiple organs at multiple timepoints, and reducing life expectancy. Treatment of this complex, rare disease is often fragmented, as patients visit specialist clinicians in isolation at different medical centres. Consequently, patients can receive sub-optimal treatment that results in decreased quality of life and a poor experience of health care systems. In 2021, we established a comprehensive clinical centre at San Raffaele Hospital, Milan, devoted to VHL disease. The centre provides a structured programme for the diagnosis, surveillance and treatment of patients alongside research into VHL disease and involves a multidisciplinary team of dedicated physicians. This programme demonstrates the benefits of care centralization, including concentration of knowledge and services, synergy and multidisciplinary management, improved networking and patient resources, reducing health care costs, and fostering research and innovation. VHL disease provides an ideal model to assess the advantages of centralizing care for rare disease and represents an unparalleled opportunity to broaden our understanding of cancer biology in general.

A case of Pitt-Hopkins syndrome: psychopharmacological approach for anxiety, insomnia, and agitation

ABSTRACT Pitt-Hopkins syndrome (PTHS) is a rare genetic disorder resulting from TCF4 gene mutations which is characterized by dysmorphic facial features, psychomotor delay, intellectual disability, breathing anomalies, and seizures. Psychiatric conditions are occasionally seen. We present the case report of a seven-year-old PTHS patient with anxiety, insomnia, and agitation. We discuss the psychopharmacological intervention options for this patient. The present case study reports on a 7-year-old female with PTHS, autism spectrum disorder (ASD), and intellectual disability. She had insomnia, crying spells and agitation complaints. For anxiety symptoms and agitation, risperidone, fluoxetine, and clonazepam treatment were given by the neurologist which caused behavioral disinhibition, paroxysmal agitation and no benefit. After admission to our hospital, aripiprazole and hydroxyzine were prescribed for anxiety and ASD-related irritability. She showed a minimal improvement but hyperventilation attacks were still ongoing. Hydroxyzine was stopped, and quetiapine was given to eliminate sleep disturbance. Her sleep period went up to eleven hours. For the anxiety symptoms, escitalopram was prescribed. She showed improvements in sleep, diminished hyperactivity and decreased frequency of abnormal breathing spells. Also, enhancement of social communication skills like increased eye contact and response to her name was observed. Patients with genetic syndromes may have various psychiatric complaints. Psychopharmacological interventions should be administered carefully for the side effects.

Hyperkinetic Movement Disorder Caused by the Recurrent c.892C>T NACC1 Variant.

Genetic syndromes of hyperkinetic movement disorders associated with epileptic encephalopathy and intellectual disability are becoming increasingly recognized. Recently, a de novo heterozygous NACC1 (nucleus accumbens-associated 1) missense variant was described in a patient cohort including one patient with a combined mitochondrial oxidative phosphorylation (OXPHOS) deficiency. The objective is to characterize the movement disorder in affected patients with the recurrent c.892C>T NACC1 variant and study the NACC1 protein and mitochondrial function at the cellular level. The movement disorder was analyzed on four patients with the NACC1 c.892C>T (p.Arg298Trp) variant. Studies on NACC1 protein and mitochondrial function were performed on patient-derived fibroblasts. All patients had a generalized hyperkinetic movement disorder with chorea and dystonia, which occurred cyclically and during sleep. Complex I was found altered, whereas the other OXPHOS enzymes and the mitochondria network seemed intact in one patient. The movement disorder is a prominent feature of NACC1-related disease.

Concordance factors in craniosynostosis twins: a meta-analysis and case report

Introductions:  Craniosynostosis is a condition where the cranial sutures close prematurely. It is influenced by both genetics and environment. This paper focuses on craniosynostosis in twins, which is an understudied area. It presents a case report of male identical twins and conducts a meta-analysis based on 34 articles to understand the factors affecting concordance in twins who have craniosynostosis. The study considers factors such as zygosity, gender, genetic syndromes, and the type of synostosis. Material and methods: A meta-analysis was conducted on 105 twin pairs (210 patients) identified from studies carried out between 1963 to 2023. The eligible studies, based on PICO criteria, included case reports and case series focusing on twins with craniosynostosis. A systematic literature search was conducted on PUBMED and Mendeley platforms to gather data on gestational age, zygosity, genetic syndromes, affected sutures, and concordance. Results: The report is about two identical twin brothers who had sagittal and metopic suture synostosis. They were treated successfully with cranial remodeling surgery. In a meta-analysis of 105 twin pairs (210 patients) , a total of 25.9% showed concordance. The study found a significant difference in concordance between monozygotic (45.3%) and dizygotic (7.3%) twins. The analysis also revealed that twins with scaphocephaly had a higher degree of concordance than those with trigonocephaly (46.7% vs. 18.9%, respectively). The study did not find any significant correlation between gender, the presence of genetic syndromes, and concordance. Conclusion: This investigation highlights the complex interplay of genetic and environmental factors in craniosynostosis in twins. The higher concordance in monozygotic twins emphasizes the genetic basis. These findings validate existing literature and provide new insights.

Spontaneous thrombosis of high flow pediatric arteriovenous fistulae: Case series of two patients and a comprehensive literature review.

Pediatric pial arteriovenous shunts in the brain and spine are challenging to understand because of low incidence, variable presentation, and associations with genetic syndromes. What is known about their natural history comes from reviews of small series. To better understand the natural history and role for intervention, two cases are presented followed by a review of the literature. In the first case, an infant with a prior history of intracranial hemorrhage from a ruptured pial fistula returns for elective embolization for a second pial fistula which was found to be spontaneously thrombosed 2weeks later. In the second case, a 5-year-old with a vertebro-vertebral fistula, identified on work up for a heart murmur and documented with diagnostic angiography, is brought for elective embolization 6weeks later where spontaneous thrombosis is identified. In reviewing the literature on pediatric single-hole fistulae of the brain and spine, the authors offer some morphologic considerations for identifying which high-flow fistulae may undergo spontaneous thrombosis to decrease the potentially unnecessary risk associated with interventions in small children.

Risk Factors for Death or Transplant After Stage 2 Palliation for Single Ventricle Heart Disease

BackgroundFor infants with single ventricle heart disease, the time after stage 2 procedure (S2P) is believed to be a lower risk period compared with the interstage period; however, significant morbidity and mortality still occur. ObjectivesThis study aimed to identify risk factors for mortality or transplantation referral between S2P surgery and the first birthday. MethodsRetrospective cohort analysis of infants in the National Pediatric Cardiology Quality Improvement Collaborative who underwent staged single ventricle palliation from 2016 to 2022 and survived to S2P. Multivariable logistic regression and classification and regression trees were performed to identify risk factors for mortality and transplantation referral after S2P. ResultsOf the 1,455 patients in the cohort who survived to S2P, 5.2% died and 2.3% were referred for transplant. Overall event rates at 30 and 100 days after S2P were 2% and 5%, respectively. Independent risk factors for mortality and transplantation referral included the presence of a known genetic syndrome, shunt type at stage 1 procedure (S1P), tricuspid valve repair at S1P, longer time to extubation and reintubation after S1P, ≥ moderate tricuspid regurgitation prior to S2P, younger age at S2P, and the risk groups identified in the classification and regression tree analysis (extracorporeal membrane oxygenation after S1P and longer S2P cardiopulmonary bypass time without extracorporeal membrane oxygenation). ConclusionsMortality and transplantation referral rates after S2P to 1 year of age remain high ∼7%. Many of the identified risk factors after S2P are similar to those established for interstage factors around the S1P, whereas others may be unique to the period after S2P.

Care pathways in childhood neurodevelopmental disorders: Toward greater awareness of KBG syndrome among pediatricians

IntroductionKBG syndrome is an autosomal dominant, polymalformative genetic syndrome that is mainly associated with neurodevelopmental and learning disorders, intellectual disability, behavioral disorders, and epilepsy as well as characteristic dysmorphic features, short stature, and ENT (ear, nose, and throat) abnormalities. However, the diagnostic pathway of these individuals is an element that has not been broadly evaluated. The main aim of this study was therefore to characterize the diagnostic pathway for these individuals, by assessing the different healthcare professionals involved and the main referral elements. MethodThis was a multicenter, retrospective, descriptive study. A cohort of 30 individuals with KBG syndrome who were followed up at Poitiers University Hospital and Bordeaux University Hospital we recruited. ResultsPediatricians were the main healthcare professionals who referred individuals for genetic consultation, and the main reason for referral was an assessment of learning delays or intellectual disability, in association with other abnormalities. ConclusionPediatricians play a crucial role in the diagnostic guidance of individuals with KBG syndrome, and the main reason for referral remains the assessment of a learning delay or intellectual disability. Healthcare professionals must therefore remain attentive to the child's development and the various anomalies associated with it, in particular characteristic dysmorphic features, behavioral disorders, and statural growth.

RASopathies for Radiologists.

RASopathies are a heterogeneous group of genetic syndromes caused by germline mutations in a group of genes that encode components or regulators of the Ras/mitogen-activated protein kinase (MAPK) signaling pathway. RASopathies include neurofibromatosis type 1, Legius syndrome, Noonan syndrome, Costello syndrome, cardiofaciocutaneous syndrome, central conducting lymphatic anomaly, and capillary malformation-arteriovenous malformation syndrome. These disorders are grouped together as RASopathies based on our current understanding of the Ras/MAPK pathway. Abnormal activation of the Ras/MAPK pathway plays a major role in development of RASopathies. The individual disorders of RASopathies are rare, but collectively they are the most common genetic condition (one in 1000 newborns). Activation or dysregulation of the common Ras/MAPK pathway gives rise to overlapping clinical features of RASopathies, involving the cardiovascular, lymphatic, musculoskeletal, cutaneous, and central nervous systems. At the same time, there is much phenotypic variability in this group of disorders. Benign and malignant tumors are associated with certain disorders. Recently, many institutions have established multidisciplinary RASopathy clinics to address unique therapeutic challenges for patients with RASopathies. Medications developed for Ras/MAPK pathway-related cancer treatment may also control the clinical symptoms due to an abnormal Ras/MAPK pathway in RASopathies. Therefore, radiologists need to be aware of the concept of RASopathies to participate in multidisciplinary care. As with the clinical manifestations, imaging features of RASopathies are overlapping and at the same time diverse. As an introduction to the concept of RASopathies, the authors present major representative RASopathies, with emphasis on their imaging similarities and differences. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Mid-term Results of Double Chamber Right Ventricle in Association with Genetic Syndromes

Double chamber right ventricle (DCRV) is a congenital disease in which a hypertrophied muscle band divides the right ventricle chamber into two. The early-mid-term follow-up of 6 patients with DCRV and distant genetic syndromes is reported in this paper. A retrospective analysis was performed of 6 DRCV patients with a mean age of 3.9±1.4 years. Concomitant cardiac anomalies were perimembranous ventricular septal defect (n=3), atrial septal defect (n=1), mild aortic regurgitation (n=1), discrete subaortic membrane (n=1). Associated genetic syndromes were Costello (n=1), Seckel (n=1) and Down syndromes (n=4). The mean follow-up period was 4.86±4.6 years. Mean systolic pressure gradient in the right ventricle in the postoperative was 18.5±11.5 mmHg. No mortality occurred and there was no requirement for reintervention. To the best of our knowledge, this is the first report in literature of concomitant DCRV with Costello and Seckel syndromes.

Echocardiographic detection of mesocardia, situs solitus associated with multiple congenital heart defects in a neonate: Rare case report

Mesocardia is a condition in which the heart is longitudinally oriented along its long axis in the midline. Cardiac position refers to the anatomical position of the left ventricular apex in the thorax. The heart has three positions: dextrocardia or right-sided heart, levocardia or left-sided heart, mesocardia or midline heart. Mesocardia is extremely rare. It represents only 0.2% of cardiac anomalies. Mesocardia is usually associated with cardiac structural abnormalities, heterotaxy syndrome, chromosomal disorders and genetic syndromes. Occasionally, it is an isolated finding. We are presenting an interesting case report of severely symptomatic neonate afflicted with mesocardia, situs solitus, moderate sized atrial septal defect (ASD) and large ventricular septal defect (VSD).

Insights into The Prenatal and Postnatal Knowledge &amp; Critical Observations of Parents with Children who Have Down Syndrome: A Single Center Study

Introduction: Down syndrome (DS) is one of the many genetic syndromes commonly confronted by pediatricians. These people commonly share a few features which include a low level of muscle tone (hypotonia), learning disabilities, and abnormalities of the cranium and facial parts. Aims and Objectives: To assess the pre and postnatal knowledge, of parents with Down syndrome children. Place and Duration of study: This descriptive cross-sectional study was conducted in Shifa International Hospital (SIH), by Final year medical students, in association with the Cytogenetics Department. between December 2019 to September 2021 Material and Methods: All the chidren diagnosed with Down Syndrome at the SIH and their parents were invited to participate in our study. Convenience sampling was used depending solely on the number of parents who had accepted our invitation. A total sample size of 35 was included, of which 15 agreed to participate. A detailed questionnaire having both close ended and open questions in English and Urdu was filled out by those parents who consented. Data was entered and analysed using SPSS version 24.0. pvalue ?0.05 was taken as significant. Results: Our results showed that 11 of the 15 DS children i.e., 73.3% were male and 4 out of 15 i.e., 26.6% were females. None of these children had siblings with the same disorder. 13 of the 15 cases (86.6%) were diagnosed post- natally only 2 cases (13.3%) pre-natally. All the cases i.e., 100% were diagnosed by a pediatrician and none were diagnosed by an obstetrician. Surprisingly increasing age of either parent seemed to increase the incidence of DS offspring. 60.0% (9 of the 15) of parents did not know the condition could be diagnosed prenatally. While 10 of 15 (66.6%) of them were aware of its general complications. Answering open ended questions parents identified the lack of awareness, special educational institutes, and presence of communication gap between them and doctors as some of the factors that hindered the welfare of DS children. Conclusion: Only one parent knew about DS complications pre-natally and only a few were aware that a pre-natal diagnosis could be formed. Postnatal knowledge of parents was sketchy also, especially regarding the future complications faced by DS children, Parents critically observed insufficient public awareness, societal taboos, paucity of local DS data and prenatal medical DS training, and consequently lack of govermnnental support required by special needs DS children in our country.

Associations between pathological features and risk of metachronous colorectal cancer.

Survivors of colorectal cancer (CRC) are at risk of developing another primary colorectal cancer - metachronous CRC. Understanding which pathological features of the first tumour are associated with risk of metachronous CRC might help tailor existing surveillance guidelines. Population-based CRC cases were recruited from the United States, Canada and Australia between 1997 and 2012 and followed prospectively until 2022 by the Colon Cancer Family Registry. Metachronous CRC was defined as a new primary CRC diagnosed at least 1 year after the initial CRC. Those with the genetic cancer predisposition Lynch syndrome or MUTYH mutation carriers were excluded. Cox regression models were fitted to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for the associations. Of 6085 CRC cases, 138 (2.3%) were diagnosed with a metachronous CRC over a median follow-up time of 12 years (incidence: 2.0 per 1000 person-years). CRC cases with a synchronous CRC were 3.4-fold more likely to develop a metachronous CRC (adjusted HR: 3.36, 95% CI: 1.89-5.98) than those without a synchronous tumour. CRC cases with MMR-deficient tumours had a 72% increased risk of metachronous CRC (adjusted HR: 1.72, 95% CI: 1.11-2.64) compared to those with MMR-proficient tumours. Compared to cases who had an adenocarcinoma histologic type, those with an undifferentiated histologic type were 77% less likely to develop a metachronous CRC (adjusted HR: 0.23, 95% CI: 0.06-0.94). Existing surveillance guidelines for CRC survivors could be updated to include increased surveillance for those whose first CRC was diagnosed with a synchronous CRC or was MMR-deficient.

Relationships between Interleukin 18 -607 C/A and -137 G/C, Osteopontin -9250 C/T Genetic Polymorphisms and Systemic Inflammatory Response Syndrome in Coronary Artery Bypass Graft Surgery

Background and Objectives: Systemic inflammatory response syndrome (SIRS) is one of the most significant complications after on-pump heart surgery procedures. High cytokine levels have been shown after open-heart surgeries and a genetic predisposition seems to be an important underlying modulatory characteristic for SIRS. To investigate the association between interleukin 18 -607 C/A, interleukin 18 -137 G/C and osteopontin 9250 C/T genetic polymorphisms and SIRS in on-pump CABG patients. Materials and Methods: Two hundred consecutive elective on-pump CABG patients were recruited prospectively to the study. Genomic DNA was extracted from whole blood and genotyping was determined by sequence specific PCR or PCR-RFLP methods for related polymorphisms. Results: SIRS incidence was 60.2%, 38.1%, 18.9% on postoperative day 1, 2 and 3, respectively, in the whole study population. The SIRS rate on the second postoperative day was 13% and 43.4%, respectively, in osteopontin 9250 C/T T allele non-carriers and carriers (p = 0.004). WBC (White Blood Cell) counts were higher on day 2 and 3 in osteopontin 9250 C/T T allele carriers compared to non-carriers (day 2; 12.7 ± 4 vs. 10.5 ± 2.4 (p = 0.015), day 3; 11.8 ± 4 vs. 9.1 ± 4.7 (p = 0.035)). The average ICU stay was 3.1 ± 7.4, 1.28 ± 0.97 for IL 18-137 G/C C allele carriers and non-carriers, respectively (p = 0.003), and in the IL 18-137 G/C C allele carriers, SIRS developed in 42.2% by the second postoperative day whereas the rate was 57.8% in non-carriers (p = 0.025). Conclusions: The current research revealed a possible link between osteopontin 9250 C/T and IL18-137 G/C genetic polymorphism and SIRS and morbidity in on-pump CABG patients.