Impact of Maternal–Fetal Environment on Mortality in Children With Single Ventricle Heart Disease

BACKGROUND Children with single ventricle heart disease have significant morbidity and mortality. The maternal–fetal environment (MFE) may adversely impact outcomes after neonatal cardiac surgery. We hypothesized that impaired MFE would be associated with an increased risk of death after stage 1 Norwood reconstruction. METHODS AND RESULTS We performed a retrospective cohort study of children with hypoplastic left heart syndrome (and anatomic variants) who underwent stage 1 Norwood reconstruction between 2008 and 2018. Impaired MFE was defined as maternal gestational hypertension, preeclampsia, gestational diabetes, and/or smoking during pregnancy. Cox proportional hazards regression models were used to investigate the association between impaired MFE and death while adjusting for confounders. Hospital length of stay was assessed with the competing risk of in‐hospital death. In 273 children, the median age at stage 1 Norwood reconstruction was 4 days (interquartile range [IQR], 3–6 days). A total of 72 children (26%) were exposed to an impaired MFE; they had more preterm births (18% versus 7%) and a greater percentage with low birth weights <2.5 kg (18% versus 4%) than those without impaired MFE. Impaired MFE was associated with a higher risk of death (hazard ratio [HR], 6.05; 95% CI, 3.59–10.21; P <0.001) after adjusting for age at surgery, Hispanic ethnicity, genetic syndrome, cardiac diagnosis, surgeon, and birth era. Children with impaired MFE had almost double the risk of prolonged hospital stay (HR, 1.95; 95% CI, 1.41–2.70; P <0.001). CONCLUSIONS Children exposed to an impaired MFE had a higher risk of death following stage 1 Norwood reconstruction. Prenatal exposures are potentially modifiable factors that can be targeted to improve outcomes after pediatric cardiac surgery.

Mapping psychosocial interventions in familial colorectal cancer: a rapid systematic review

Background Approximately 5% of colorectal cancer (CRC) cases are part of a well-defined inherited genetic syndrome and up to approximately 30% of these cases have a clinically defined familial basis. Psychosocial interventions in familial colorectal cancer address aspects mainly focused on affective, cognitive and behavioural outcomes. The present review aims to systematically map out the available psychosocial interventions for individuals with a family history of CRC and describe the current state of the research. Methods An extensive electronic search was conducted to investigate the literature published until June 2020. Inclusion criteria consisted of quantitative studies published in English that explored the impact of psychosocial interventions for familial CRC, clearly defined the psychosocial intervention offered and included participants with a family history of CRC. Results The analysis included 52 articles. Genetic counselling, educational interventions, psychological interventions and multimodal interventions were identified across the studies. In terms of diagnoses, Lynch Syndrome, Familial Adenomatous Polyposis, Familial Colorectal Cancer were the main conditions included in the studies. Affective, cognitive, behavioural aspects and quality of life emerged as the most frequently explored outcomes. The studies included individuals with both personal and familial history of CRC or family history alone. Conclusions Our rapid review provides an overview of the literature exploring the impact of psychosocial interventions for familial CRC. The psychosocial interventions identified had an overwhelmingly positive impact across all types of outcomes measured. Genetic counselling appeared to be most beneficial, and this is expected as it is purposively designed to address genetic conditions. Further quantitative analysis of primary empirical research is needed to determine the efficacy and effectiveness of psychosocial interventions as well as the mechanisms through which they exert their effect.

Rare Genetic Syndromes and Oral Anomalies: A Review of the Literature and Case Series with a New Classification Proposal

Rare genetic syndromes, conditions with a global average prevalence of 40 cases/100,000 people, are associated with anatomical, physiological, and neurological anomalies that may affect different body districts, including the oral district. So far, no classification of oral abnormalities in rare genetic syndromes is present in the literature. The aim of this narrative review is to analyze literature on rare genetic syndromes affecting dento-oro-maxillofacial structures (teeth, maxillary bones, oral soft tissues, or mixed) and to propose a classification according to the detected oral abnormalities. In addition, five significant cases of rare genetic syndromes are presented. The Scale for the Assessment of Narrative Review Articles (SANRA) was followed for this review. From 674 papers obtained through PubMed search, 351 were selected. Sixty-two rare genetic syndromes involving oral manifestations were found and classified. The proposed classification aims to help the clinician to easily understand which dento-oro-maxillofacial findings might be expected in the presence of each rare genetic syndrome. This immediate framework may both help in the diagnosis of dento-oro-maxillofacial anomalies related to the underlying pathology as well as facilitate the drafting of treatment plans with the involvement of a multidisciplinary team.

PRADER-WILLI SYNDROME: A CLINICAL CASE

Синдром Прадера-Вилли - редкое наследственное заболевание, причиной которого является отсутствие отцовской копии участка хромосомы 15q11-13. Одним из проявлений данного генетического синдрома может быть соматотропная недостаточность. Именно низкорослость часто является поводом для обращения родителей пациента к врачу-эндокринологу. Для своевременной диагностики заболевания очень важен командный подход специалистов с участием генетика, эндокринолога, невропатолога с обязательным проведением генетического анализа. Обнаружение дефицита гормона роста и назначение соответствующей заместительной терапии повышает уровень медицинской и социальной адаптации ребенка. В данной статье описан случай синдрома Прадера-Вилли с соматотропной недостаточностью у 4-летней девочки, представлены преимущества и риски применения гормона роста. Prader-Willi syndrome is a rare hereditary disorder caused by the absence of a paternal copy of the 15q11-13 chromosome region. One of the manifestations of this genetic syndrome may be somatotropic insufficiency. It is the short stature that is often the reason for the patient's parents to contact an endocrinologist. For the timely diagnosis of the disease, a team approach of specialists with the participation of a geneticist, endocrinologist, neuropathologist with the obligatory genetic analysis is very important. Detection of growth hormone deficiency and the appointment of appropriate substitution therapy increases the level of medical and social adaptation of the child. This article describes a case of Prader-Willi syndrome with growth hormone deficiency in a 4-year-old girl, presents the benefits and risks of using growth hormone.

Hypogonadism in Women with Prader-Willi Syndrome—Clinical Recommendations Based on a Dutch Cohort Study, Review of the Literature and an International Expert Panel Discussion

Prader-Willi syndrome (PWS) is a rare neuroendocrine genetic syndrome. Characteristics of PWS include hyperphagia, hypotonia, and intellectual disability. Pituitary hormone deficiencies, caused by hypothalamic dysfunction, are common and hypogonadism is the most prevalent. Untreated hypogonadism can cause osteoporosis, which is already an important issue in PWS. Therefore, timely detection and treatment of hypogonadism is crucial. To increase understanding and prevent undertreatment, we (1) performed a cohort study in the Dutch PWS population, (2) thoroughly reviewed the literature on female hypogonadism in PWS and (3) provide clinical recommendations on behalf of an international expert panel. For the cohort study, we retrospectively collected results of a systematic health screening in 64 female adults with PWS, which included a medical questionnaire, medical file search, medical interview, physical examination and biochemical measurements. Our data show that hypogonadism is frequent in females with PWS (94%), but is often undiagnosed and untreated. This could be related to unfamiliarity with the syndrome, fear of behavioral changes, hygienic concerns, or drug interactions. To prevent underdiagnosis and undertreatment, we provide practical recommendations for the screening and treatment of hypogonadism in females with PWS.

Prevalence of Hypodontia in Saudi Arabia: A Retrospective Digital Orthopantomographic Study

Introduction: Hypodontia or Dental agenesis; is defined as a developmental missing of any teeth, excluding the last molars. It may befall as a genetic syndrome or as a non-syndromic isolated trait. However, there is no prevalence available in our city. Aim and Objectives: The tenacity of this research is to assess the frequency of hypodontia among the population who received dental care at King Abdul Aziz University Dental Hospital in the city of Jeddah. Study Design: Retrospective digital orthopantomographic: cross-sectional study. Place and Duration of Study: Oral & Maxillofacial Prosthodontic Department, King Abdulaziz University, between January 2019 and July 2020. Methodology: This research is a retrospective cross-sectional study based on the examination of an archival dental record and 2D panoramic radiographs of patients who are presented at King Abdulaziz University Dental Hospital, Jeddah. A total of 2045 records were reviewed and included in this study. Two general practitioners reviewed patient’s dental charts looking for congenital missing tooth/teeth in a dark room by the method that the practitioners use. Careful reviews of each patient’s record were done to ensure that the cause of the missing tooth/teeth were congenital and not surgical or traumatic. Data were gathered from dental records of patients’ age period 6-9 years since most of the dental follicle of the permanent teeth should be completed or the tooth just erupts, radiographic findings were always compared to the patients’ file and progress notes to ensure the causative factors of missing teeth. The data were recorded in an excel sheet which included gender, age, the type, area and counting of the missing teeth. Results: After collecting the data, the total number of patients after exclusion were 1984. The prevalence of hypodontia in our tested population was %5.39. Statistical analysis were done by using SPSS software to correlate between variables. Varices grades. Conclusion: Within the limitations of this study our data shows that the most common congenitally tooth agenesis is the second premolar %47.6 and the second most common congenitally missing tooth is lateral incisor %18.6.

A Case of Microsatellite Instability–High Colon Cancer in a Young Woman With Familial Adenomatous Polyposis

Two major molecular pathways of colorectal carcinogenesis, chromosomal instability (CIN) and microsatellite instability (MSI), are considered to be mutually exclusive. Distinguishing CIN from MSI-high tumors has considerable therapeutic implications, because patients with MSI-high tumors can derive considerable benefit from immune checkpoint inhibitors, and tumors that evolved through the CIN pathway do not respond to these agents. Familial adenomatous polyposis (FAP) is a genetic syndrome that is defined by a mutation in the APC gene and is thought to lead to carcinogenesis through the CIN pathway. Here, we report a case of a young woman with FAP who was treated for medulloblastoma as a child and developed advanced MSI-high colon cancer as a young adult. Her response to second-line immunotherapy enabled resection of her colon cancer, and she is free of disease >10 months after surgery. This case highlights the potential for overlap between the CIN and MSI carcinogenic pathways and associated therapeutic implications.

Syndromic Monogenic Diabetes Genes Should be Tested in Patients With a Clinical Suspicion of MODY

At present, outside of infancy, genetic testing for monogenic diabetes is typically for mutations in MODY genes that predominantly result in isolated diabetes. Monogenic diabetes syndromes are usually only tested when this is supported by specific syndromic clinical features. It is not known how frequently patients with suspected MODY have a mutation in a monogenic syndromic diabetes gene and thus missed by present testing regimes. We performed<b> </b>genetic testing of 27 monogenic diabetes genes (including 18 associated with syndromic diabetes) for 1280 patients with a clinical suspicion of MODY from routine clinical care that were not suspected of having monogenic syndromic diabetes. We confirmed monogenic diabetes in 297 (23%) patients. Mutations in 7 different syndromic diabetes genes accounted for 19% (95%CI 15-24%) of all monogenic diabetes. The mitochondrial m.3243A>G and mutations in <i>HNF1B</i> were responsible for the majority of mutations in syndromic diabetes genes. They were also the 4^th and 5^th most common causes of monogenic diabetes overall. These patients lacked typical features and their diabetes phenotypes overlapped with non-syndromic monogenic diabetes patients. Syndromic monogenic diabetes genes (particularly m.3243A>G and <i>HNF1B</i>) should be routinely tested in patients with suspected MODY that do not have typical features of a genetic syndrome.

Syndromic Monogenic Diabetes Genes Should be Tested in Patients With a Clinical Suspicion of MODY

At present, outside of infancy, genetic testing for monogenic diabetes is typically for mutations in MODY genes that predominantly result in isolated diabetes. Monogenic diabetes syndromes are usually only tested when this is supported by specific syndromic clinical features. It is not known how frequently patients with suspected MODY have a mutation in a monogenic syndromic diabetes gene and thus missed by present testing regimes. We performed<b> </b>genetic testing of 27 monogenic diabetes genes (including 18 associated with syndromic diabetes) for 1280 patients with a clinical suspicion of MODY from routine clinical care that were not suspected of having monogenic syndromic diabetes. We confirmed monogenic diabetes in 297 (23%) patients. Mutations in 7 different syndromic diabetes genes accounted for 19% (95%CI 15-24%) of all monogenic diabetes. The mitochondrial m.3243A>G and mutations in <i>HNF1B</i> were responsible for the majority of mutations in syndromic diabetes genes. They were also the 4^th and 5^th most common causes of monogenic diabetes overall. These patients lacked typical features and their diabetes phenotypes overlapped with non-syndromic monogenic diabetes patients. Syndromic monogenic diabetes genes (particularly m.3243A>G and <i>HNF1B</i>) should be routinely tested in patients with suspected MODY that do not have typical features of a genetic syndrome.

Xeroderma Pigmentosum: General Aspects and Management

Xeroderma Pigmentosum (XP) is a rare genetic syndrome with a defective DNA nucleotide excision repair. It is characterized by (i) an extreme sensitivity to ultraviolet (UV)-induced damages in the skin and eyes; (ii) high risk to develop multiple skin tumours; and (iii) neurologic alterations in the most severe form. To date, the management of XP patients consists of (i) early diagnosis; (ii) a long-life protection from ultraviolet radiation, including avoidance of unnecessary UV exposure, wearing UV blocking clothing, and use of topical sunscreens; and (iii) surgical resections of skin cancers. No curative treatment is available at present. Thus, in the last decade, in order to prevent or delay the progression of the clinical signs of XP, numerous strategies have been proposed and tested, in some cases, with adverse effects. The present review provides an overview of the molecular mechanisms featuring the development of XP and highlights both advantages and disadvantages of the clinical approaches developed throughout the years. The intention of the authors is to sensitize scientists to the crucial aspects of the pathology that could be differently targeted. In this context, the exploration of the process underlining the conception of liposomal nanocarriers is reported to focus the attention on the potentialities of liposomal technology to optimize the administration of chemoprotective agents in XP patients.