Anesthesia for the Patient with a Genetic Syndrome

Lynch syndrome (LS) is a common genetic syndrome characterized by pathogenic mutations of DNA mismatch repair genes resulting in a hereditary predisposition to cancer. While typically associated with colonic and endometrial cancer, LS additionally influences the development of many other malignancies. The Amsterdam II and Revised Bethesda Guidelines are the established clinical criteria for diagnosing LS. These guidelines are based on the most general characteristics of LS and do not address specific characteristics of the less commonly LS-associated malignancies. For individuals that present initially with a non-colon and non-endometrial malignancy, recommendations and guidelines on when to consider screening for LS are limited. Therefore, it is essential that clinicians are familiar with distinct LS-associated patient- and tumor-specific characteristics, especially of the less common LS-associated cancers, so that LS’s diagnosis is not missed. In this review article, we focus on extra-colonic and extra-endometrial LS-associated cancers, paying particular attention to any established or currently investigated cancer features that help raise suspicion for LS and potentially lead to its earlier diagnosis. This review will also discuss current guidelines specific to each LS-associated malignancy.

Download Full-text

Autoimmunity and Genetic Syndromes: A Focus on Down Syndrome

Genes ◽

10.3390/genes12020268 ◽

2021 ◽

Vol 12 (2) ◽

pp. 268

Author(s):

Marta Ferrari ◽

Stefano Stagi

Keyword(s):

Down Syndrome ◽

Autoimmune Diseases ◽

Normal Population ◽

Underlying Mechanism ◽

Short Review ◽

Immune Dysregulation ◽

Infectious Complications ◽

Genetic Syndromes ◽

Genetic Syndrome

Within immune system-related diseases, autoimmunity has always represented a field of great interest, although many aspects remain poorly understood even today. Genetic syndromes associated with immunity disorders are common and represent an interesting model for a better understanding of the underlying mechanism of autoimmunity predisposition. Among these conditions, Down syndrome (DS) certainly deserves special attention as it represents the most common genetic syndrome associated with immune dysregulation, involving both innate and adaptive immunity. Autoimmunity represents a well-known complication of DS: it is estimated that people affected by this disease present a risk four to six times higher than the normal population to develop autoimmune diseases such as celiac disease, type 1 diabetes mellitus, and hypo- or hyperthyroidism. Several factors have been considered as possible etiology, including genetic and epigenetic modifications and immune dysregulation. In times in which the life expectancy of people with DS has been extremely prolonged, thanks to improvements in the diagnosis and treatment of congenital heart disease and infectious complications, knowledge of the mechanisms and proper management of autoimmune diseases within this syndrome has become essential. In this short review, we aim to report the current literature regarding the genetic, immune, and environmental factors that have been proposed as the possible underlying mechanism of autoimmunity in individuals with DS, with the intent to provide insight for a comprehensive understanding of these diseases in genetic syndromes.

Download Full-text

Gastrostomy Tube Placement in Neonates Undergoing Congenital Heart Surgery: A Novel Assessment for Improving Utilization and Timing of Placement

World Journal for Pediatric and Congenital Heart Surgery ◽

10.1177/21501351211003103 ◽

2021 ◽

Vol 12 (4) ◽

pp. 480-486

Author(s):

Kevin M. Beers ◽

Aaron Bettenhausen ◽

Thomas J. Prihoda ◽

John H. Calhoon ◽

S. Adil Husain

Keyword(s):

Length Of Stay ◽

Aortic Arch ◽

Congenital Heart ◽

Gastrostomy Tube ◽

Tube Placement ◽

Genetic Syndrome ◽

Delayed Sternal Closure ◽

Aortic Arch Reconstruction ◽

Gastrostomy Tube Placement ◽

Arch Reconstruction

Background: Neonates undergoing congenital heart defect repair require optimized nutritional support in the perioperative period. Utilization of a gastrostomy tube is not infrequent, yet optimal timing for placement is ill-defined. The objective of this study was to identify characteristics of patients whose postoperative course included gastrostomy tube placement to facilitate supplemental tube feeding following neonatal repair of congenital heart defects. Methods: A single-institution, retrospective chart review identified 64 consecutive neonates who underwent cardiac operations from 2012 to 2016. Perioperative variables were evaluated for significance in relation to gastrostomy tube placement. Results: A total of 27 (42%) underwent gastrostomy tube placement. Diagnosis of a genetic syndrome was associated with the likelihood of placement of gastrostomy tube ( P = .032), as were patients with single ventricle physiology ( P = .0013) compared to those felt to be amenable to eventual biventricular repair. Aortic arch reconstruction ( P = .029), as well as the need for delayed sternal closure ( P = .05), was associated with increased frequency of gastrostomy tube placement. Postoperative outcomes including the number of days intubated ( P = .0026) and the presence of significant dysphagia ( P = .0034) were associated with gastrostomy placement. Additionally, genetic syndrome ( P = .003), aortic arch reconstruction ( P = .01), and postoperative intubation duration ( P = .0024) correlated with increased length of stay, where increased length of stay was associated with gastrostomy tube placement ( P = .0004). Discussion: Patient characteristics that were associated with a high likelihood of eventual gastrostomy placement were identified in this study. Early recognition of such characteristics in future patients may allow for reduced time to gastrostomy tube placement, which in turn may improve perioperative growth and outcomes.

Download Full-text

Proteus syndrome in pregnancy: A case report

Obstetric Medicine ◽

10.1177/1753495x20970791 ◽

2020 ◽

pp. 1753495X2097079

Author(s):

Niccole Ranaei-Zamani ◽

Mandeep K Kaler ◽

Rehan Khan

Keyword(s):

Case Report ◽

Case Reports ◽

Proteus Syndrome ◽

Cutaneous Lesions ◽

Genetic Syndrome ◽

Skeletal Tissue ◽

First Case ◽

Large Teaching Hospital ◽

Clinical Presentations ◽

In Pregnancy

Proteus syndrome is a rare, multi-system, genetic syndrome characterised by atypical and excessive growth of skeletal tissue. Clinical presentations include abnormal musculoskeletal growth and cutaneous lesions. Due to its rarity, there have been a limited number of published case reports of Proteus syndrome. This is the first case report on the management of Proteus syndrome in pregnancy. We present the case of a pregnant woman with Proteus syndrome in her first pregnancy in a large teaching hospital and discuss the considerations and challenges faced in her antenatal, intrapartum and postnatal care.

Download Full-text

Young children with Noonan syndrome: evaluation of feeding problems

European Journal of Pediatrics ◽

10.1007/s00431-020-03664-x ◽

2020 ◽

Vol 179 (11) ◽

pp. 1683-1688

Author(s):

Jos M. T. Draaisma ◽

Joris Drossaers ◽

Lenie van den Engel-Hoek ◽

Erika Leenders ◽

Joyce Geelen

Keyword(s):

Young Children ◽

Noonan Syndrome ◽

Early Onset ◽

Late Onset ◽

Tube Feeding ◽

Genetic Mutation ◽

First Year ◽

Feeding Problems ◽

Genetic Syndrome ◽

First Year Of Life

Abstract Noonan syndrome (NS) is a common genetic syndrome with a high variety in phenotype. Even though genetic testing is possible, NS is still a clinical diagnosis. Feeding problems are often present in infancy. We investigated the feeding status of 108 patients with clinically and genetically confirmed NS. Only patients with a documented feeding status before the age of 6 were included. A distinction was made between patients with early onset feeding problems (< 1 year) and children with late onset feeding problems (> 1 year). Seventy-one of 108 patients had feeding problems, of which 40 patients required tube feeding. Children with a genetic mutation other than PTPN11 and SOS1 had significantly more feeding problems in the first year. Fifty-two of all 108 patients experienced early onset feeding problems, of which 33 required tube feeding. A strong decrease in prevalence of feeding problems was found after the first year of life. Fifteen children developed feeding problems later in life, of which 7 required tube feeding. Conclusion: Feeding problems occur frequently in children with NS, especially in children with NS based on genetic mutations other than PTPN11 and SOS1. Feeding problems develop most often in infancy and decrease with age. What is Known:• Young children with Noonan syndrome may have transient feeding problems.• Most of them will need tube feeding. What is New:• This is the first study of feeding problems in patients with clinically and genetically proven Noonan syndrome.• Feeding problems most often develop in infancy and resolve between the age of 1 and 2.

Download Full-text

Congenital hypertrichosis, osteochondrodysplasia, and cardiomegaly: Further delineation of a new genetic syndrome

American Journal of Medical Genetics ◽

10.1002/(sici)1096-8628(19970317)69:2<138::aid-ajmg5>3.0.co;2-l ◽

1997 ◽

Vol 69 (2) ◽

pp. 138-151 ◽

Cited By ~ 23

Author(s):

D. García-Cruz ◽

J. Sánchez-Corona ◽

Z. Nazará ◽

M. O. García-Cruz ◽

L. E. Figuera ◽

...

Keyword(s):

Genetic Syndrome

Download Full-text

Monogenic Syndromes with Congenital Heart Diseases in Newborns (Diagnostic Clues for Neonatologists): A Critical Analysis with Systematic Literature Review

Journal of Pediatric Genetics ◽

10.1055/s-0041-1731036 ◽

2021 ◽

Author(s):

Raffaele Falsaperla ◽

Valentina Giacchi ◽

Maria Giovanna Aguglia ◽

Janette Mailo ◽

Maria Grazia Longo ◽

...

Keyword(s):

Systematic Review ◽

Congenital Heart ◽

Heart Diseases ◽

Cost Effective ◽

Monogenic Disease ◽

Chromosomal Anomalies ◽

Genetic Syndrome ◽

Wide Range ◽

Major Congenital Anomaly ◽

Genomic Disorders

AbstractCongenital heart disease (CHD), the most common major congenital anomaly, is associated with a genetic syndrome (chromosomal anomalies, genomic disorders, or monogenic disease) in 30% of patients. The aim of this systematic review is to evaluate if, in the neonatal setting, clinical clues that orient the diagnostic path can be identified. For this purpose, we revised the most frequent dysmorphic features described in newborns with CHD, comparing those associated with monogenic syndromes (MSG) with the ones reported in newborns with genomic disorders. For this systematic review according to PRISMA statement, we used PubMed, Medline, Google Scholar, Scopus database, and search terms related to CHD and syndrome. We found a wide range of dysmorphisms (ocular region, ears, mouth, and/or palate and phalangeal anomalies) detected in more than half of MSGs were found to be associated with CHDs, but those anomalies are also described in genomic rearrangements syndromes with equal prevalence. These findings confirm that etiological diagnosis in newborns is challenging, and only the prompt and expert recognition of features suggestive of genetic conditions can improve the selection of appropriate, cost-effective diagnostic tests. However, in general practice, it is crucial to recognize clues that can suggest the presence of a genetic syndrome, and neonatologists often have the unique opportunity to be the first to identify abnormalities in the neonate.

Download Full-text

Abstract 16822: Growth Curves Describing a Single Ventricle Population After Fontan Procedure

Circulation ◽

10.1161/circ.142.suppl_3.16822 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Bethany Runkel ◽

Vincent Staggs ◽

Chelsea Hosey Cojocari ◽

Jonathan B Wagner

Keyword(s):

Single Ventricle ◽

Multiple Stressors ◽

Pediatric Population ◽

Fontan Procedure ◽

Fontan Operation ◽

Growth Patterns ◽

Growth Charts ◽

Genetic Syndrome ◽

Adiposity Rebound ◽

Extracardiac Conduit

Introduction: Complex single ventricle congenital heart disease (CHD) patients are subject to multiple stressors early in life that affect somatic growth. Pre-Fontan growth patterns are well-described, but post-Fontan growth has not been extensively studied in the current era. We sought to describe post-Fontan growth patterns by creating sex-specific body mass index (BMI)-for-age curves. Hypothesis: There is no difference in the growth of post-Fontan pediatric patients when compared to published normative data. Methods: A single-center, preexisting database was retrospectively queried for all patients who underwent Fontan procedure between 2006 and 2018. Patients with a genetic syndrome, a primary endocrine disorder, or significant prematurity were excluded. BMI-for-age curves were created for both male and female patients using anthropometric data extracted from the electronic medical record. Curves were then visually compared with Centers for Disease Control and Prevention (CDC) growth charts. Results: Of 227 patients who underwent primary Fontan operation, 37 were excluded. Of the remaining 190 patients, 59% were male. All had an extracardiac conduit, half had right-ventricular dominant CHD, and 15% had a Fontan fenestration. Median age and weight at surgery were 3.9 years and 15 kilograms, respectively. BMI curves were similar in appearance to CDC BMI-for-age growth charts, with adiposity rebound at age 6. BMI increased more rapidly in teen boys compared with girls, and a total of five patients (2.6%) had BMI values greater than 25 kg/m 2 at 16 years of age. Conclusion: Post-Fontan patients at our institution demonstrate BMI-for-age patterns similar to those of the general population during childhood and early adolescence, with adiposity rebound occurring at a typical age. Though excess weight gain does not completely spare patients with single ventricle CHD, overweight status appears to be less common than in the general pediatric population.

Download Full-text