Congenital Heart Disease with Congenital Diaphragmatic Hernia: Surgical Decision Making and Outcomes.

OBJECTIVE: To describe the types of congenital heart disease (CHD) in a congenital diaphragmatic hernia (CDH) cohort in a large volume center and evaluate surgical decision making and outcomes based on complexity of CHD and associated conditions. STUDY DESIGN: A retrospective review of patients with CHD and CDH diagnosed by echocardiogram between 01/01/2005 and 07/31/2021. The cohort was divided into 2 groups based on survival at discharge. RESULTS: Clinically important CHD was diagnosed in 19% (62/326) of CDH patients. There was 90% (18/20) survival in children undergoing surgery for both CHD and CDH as neonates, and 87.5 (22/24) in those undergoing repair initially for CDH alone. A genetic anomaly identified on clinical testing was noted in 16% with no significant association with survival. A higher frequency of other organ system anomalies was noted in nonsurvivors compared with survivors. Nonsurvivors were more likely to have unrepaired CDH (69% vs 0%, P < .001) and unrepaired CHD (88% vs 54%, P < .05), reflecting a decision not to offer surgery. CONCLUSIONS: Survival was excellent in patients who underwent repair of both CHD and CDH. Patients with univentricular physiology have poor survival and this finding should be incorporated into pre and postnatal counseling about eligibility for surgery. In contrast, patients with other complex lesions including transposition of the great arteries have excellent outcomes and survival at 5 years follow-up at a large pediatric and cardiothoracic surgical center.

Mother and Daughter Perspectives on Genetic Counseling and Testing of Adolescents for Hereditary Breast Cancer Risk.

OBJECTIVE: To evaluate the risks, benefits, and utility of testing for adult-onset hereditary breast and ovarian cancer (HBOC) in adolescents and young adults. STUDY DESIGN: We evaluated interest in genetic testing of adolescents for adult-onset HBOC genes through semistructured interviews with mothers and adolescents who had previously participated in breast cancer research or had pursued (mothers) clinical testing for HBOC. RESULTS: The majority of mothers (73%) and daughters (75%) were interested in the daughter having genetic testing and were motivated by the future medical utility and current social utility of relieving anxiety and allowing them to prepare. Mothers and daughters both reported that approximately 3 years in the future was the best time to test the daughter regardless of the current age of the daughter. Overall, both mothers and daughters expressed the importance of the involvement of the mother to provide educational and emotional support but ultimately it was the daughter's decision to test. Balancing the independence and maturity of the daughter while reinforcing communication and support within the dyad was a prominent theme throughout the interviews. CONCLUSIONS: There is interest among some high-risk adolescents and young adults to engage in genetic counseling and undergo testing. Providing pretest and posttest genetic counseling, assessing preferences for parent involvement, and offering psychosocial support may be important if genetic testing for HBOC is offered to adolescents and young adults before age 25 years.

SARS-CoV-2 Infection in Patients with Down Syndrome, Congenital Heart Disease, and Pulmonary Hypertension: Is Down Syndrome a Risk Factor?

With increasing information available about the epidemiology, pathophysiology, and management of patients affected with severe acute respiratory syndrome corona virus-2 infection, patients with Down syndrome, congenital heart disease, airway obstruction, and pulmonary hypertension present a unique challenge. This case series describes 3 patients with Down syndrome and respiratory failure secondary to coronavirus infection.

ACSS2 gene variant associated with cleft lip and palate in two independent Hispanic populations.

OBJECTIVES/HYPOTHESIS: A candidate variant (p.Val496Ala) of the ACSS2 gene (T > C missense, rs59088485 variant at chr20: bp37 33509608) was previously found to consistently segregate with nonsyndromic cleft lip and/or palate (NSCLP) in three Honduran families. Objectives of this study were 1) to investigate the frequency of this ACSS2 variant in Honduran unrelated NSCLP patients and unrelated unaffected controls and 2) to investigate the frequency of this variant in Colombian unrelated affected NSCLP patients and unrelated unaffected controls. STUDY DESIGN: Case-control studies. METHODS: Sanger sequencing of 99 unrelated Honduran NSCLP patients and 215 unrelated unaffected controls for the p.Val496Ala ACSS2 variant was used to determine the carrier frequency in NSCLP patients and controls. Sanger sequencing of 230 unrelated Colombian NSCLP patients and 146 unrelated unaffected controls for the p.Val496Ala ACSS2 variant was used to determine the carrier frequency in NSCLP patients and controls. RESULTS: In the Honduran population, the odds ratio of having NSCLP among carriers of the p.Val496Ala ACSS2 variant was 4.0 (P = .03), with a carrier frequency of seven of 99 (7.1%) in unrelated affected and four of 215 (1.9%) in unrelated unaffected individuals. In the Colombian population, the odds ratio of having NSCLP among carriers of the p.Val496Ala ACSS2 variant was 2.6 (P = .04), with a carrier frequency of 23 of 230 (10.0%) in unrelated affected and six of 146 (4.1%) in unrelated unaffected individuals. CONCLUSIONS: These findings support the role of ACSS2 in NSCLP in two independent Hispanic populations from Honduras and Colombia. LEVEL OF EVIDENCE: NA Laryngoscope, 127:E336-E339, 2017.

Male-to-Male Sexual Transmission of Zika Virus--Texas, January 2016.

Zika virus infection has been linked to increased risk for Guillain-Barré syndrome and adverse fetal outcomes, including congenital microcephaly. In January 2016, after notification from a local health care provider, an investigation by Dallas County Health and Human Services (DCHHS) identified a case of sexual transmission of Zika virus between a man with recent travel to an area of active Zika virus transmission (patient A) and his nontraveling male partner (patient B). At this time, there had been one prior case report of sexual transmission of Zika virus. The present case report indicates Zika virus can be transmitted through anal sex, as well as vaginal sex. Identification and investigation of cases of sexual transmission of Zika virus in nonendemic areas present valuable opportunities to inform recommendations to prevent sexual transmission of Zika virus.

Pertussis: a persistent cause of morbidity and mortality in young infants.

In 2012, a pertussis outbreak in Dallas County resulted in the deaths of 4 children (3, unvaccinated; 2, <60 days of age). Despite recommendations that include immunization of women preferably during the third trimester of pregnancy or postpartum, household contacts ("cocooning"), and infants as early as 42 days of age, challenges in pertussis prevention remain.

Prompt control of an outbreak caused by extended-spectrum ß-lactamase-producing Klebsiella pneumoniae in a neonatal intensive care unit.

OBJECTIVES: To assess the effectiveness of a set of multidisciplinary interventions aimed at limiting patient-to-patient transmission of extended-spectrum ß-lactamase-producing Klebsiella pneumoniae (ESBL-KP) during a neonatal intensive care unit (NICU) outbreak, and to identify risk factors associated with ESBL-KP colonization and disease in this setting. STUDY DESIGN: A 61-infant cohort present in the NICU during an outbreak of ESBL-KP from April 26, 2011, to May 16, 2011, was studied. Clinical characteristics were compared in infected/colonized infants and unaffected infants. A multidisciplinary team formulated an outbreak control plan that included (1) staff reeducation on recommended infection prevention measures; (2) auditing of hand hygiene and environmental services practices; (3) contact precautions; (4) cohorting of infants and staff; (5) alleviation of overcrowding; and (6) frequent NICU-wide screening cultures. Neither closure of the NICU nor culturing of health care personnel was instituted. RESULTS: Eleven infants in this level III NICU were infected/colonized with ESBL-KP. The index case was an 18-day-old infant born at 25 weeks' gestation who developed septicemia from ESBL-KP. Two other infants in the same room developed sepsis from ESBL-KP within 48 hours; both expired. Implementation of various infection prevention strategies resulted in prompt control of the outbreak within 3 weeks. The ESBL-KP isolates presented a single clone that was distinct from ESBL-KP identified previously in other units. Being housed in the same room as the index infant was the only risk factor identified by logistic regression analysis (P = .002). CONCLUSION: This outbreak of ESBL-KP affected 11 infants and was associated with 2 deaths. Prompt control with eradication of the infecting strain from the NICU was achieved with multidisciplinary interventions based on standard infection prevention practices.

Outcomes of congenital diaphragmatic hernia in the modern era of management.

OBJECTIVE: To identify clinical factors associated with pulmonary hypertension (PH) and mortality in patients with congenital diaphragmatic hernia (CDH). STUDY DESIGN: A prospective cohort of neonates with a diaphragm defect identified at 1 of 7 collaborating medical centers was studied. Echocardiograms were performed at 1 month and 3 months of age and analyzed at a central core by 2 cardiologists independently. Degree of PH and survival were tested for association with clinical variables using Fischer exact test, χ(2), and regression analysis. RESULTS: Two hundred twenty patients met inclusion criteria. Worse PH measured at 1 month of life was associated with higher mortality. Other factors associated with mortality were need for extracorporeal membrane oxygenation, patients inborn at the treating center, and patients with a prenatal diagnosis of CDH. Interestingly, patients with right sided CDH did not have worse outcomes. CONCLUSIONS: Severity of PH is associated with mortality in CDH. Other factors associated with mortality were birth weight, gestational age at birth, inborn status, and need for extracorporeal membrane oxygenation.

Association of candidate genes with nonsyndromic clefts in Honduran and Colombian populations.

OBJECTIVES/HYPOTHESIS: Orofacial clefts are the most common craniofacial birth defects in humans, with the majority of orofacial clefts occurring as nonsyndromic cleft lip with or without cleft palate (NSCLP). We previously demonstrated associations between single-nucleotide polymorphisms (SNPs) in the IRF6 gene and NSCLP in the Honduran population. Here we investigated other candidate genes and chromosomal regions associated with NSCLP identified from genome-wide association studies (GWAS), including MAFB, ABCA4, 8q24, 9q22, 10q25, and 17q22 in two independent Hispanic populations. STUDY DESIGN: Case-control and family-based association testing. METHODS: Honduran families with two or more members with NSCLP (multiplex) were identified. DNA was collected from affected and unaffected family members (488) and 99 gender-matched controls. NSCLP Colombian families were identified; DNA was collected from 26 proband-parent trios. All participants were genotyped for 17 SNPs in six chromosomal regions. Case-control association and family-based association testing (FBAT) analyses were conducted. RESULTS: Seven SNPs demonstrated association in at least one model in the Honduran population. In the Colombian families, five SNPs demonstrated significance in FBAT when patients with isolated cleft palate (CP) were included; four overlapped with SNPs demonstrating significance in the Honduran population, two with the same allele. One SNP retained significance with CP excluded. CONCLUSIONS: This study supports the previous GWAS findings and is the first to suggest a role for FOXE1, ABCA4, and MAFB in orofacial clefting in two separate Hispanic populations.

Mild fasting hyperglycemia in children: high rate of glucokinase mutations and some risk of developing type 1 diabetes mellitus.

BACKGROUND: Incidental hyperglycemia in children generates concern about the presence of preclinical type 1 diabetes mellitus (T1DM). OBJECTIVE: To genetically evaluate two common forms of maturity-onset diabetes of youth (MODY), the short-term prognosis in children with mild hyperglycemia, and a positive family history of diabetes mellitus. SUBJECTS: Asymptomatic children and adolescents (n = 14), younger than 15 yr, with fasting hyperglycemia, a positive family history of mild non-progressive hyperglycemia, and negative pancreatic autoantibodies were studied. PATIENTS AND METHODS: Glucokinase gene (GCK) and hepatocyte nuclear factor 1 alpha gene (HNF1A) causing two common forms of MODY were sequenced. The clinical outcome was evaluated after a follow-up period of 2.8 +/- 1.3 yr. RESULTS: GCK mutations were present in seven children. The confirmation of this diagnosis allowed discontinuation of insulin in two families and oral medications in three families. Mutations of HNF1A were not detected in any of the families. During the follow-up period, all the GCK mutation carrier children remained asymptomatic without medication and the last hemoglobin A1c levels were 6.4 +/- 0.7%. In the GCK-negative children (n = 7), one developed T1DM, corresponding to 7.2% of the total group. Mild fasting hyperglycemia persisted during follow-up in four GCK-negative children and normalized in the remaining two. CONCLUSIONS: The presence of mild persistent hyperglycemia in any patient without autoantibodies should lead to genetic analysis of GCK, particularly if there is a positive family history. Furthermore, those without GCK mutations should be followed with repeat autoantibody testing, and other genetic types of diabetes should be considered if hyperglycemia worsens.

Glucokinase mutations in young children with hyperglycemia.

BACKGROUND: The etiology of mild hyperglycemia without ketoacidosis in young children is often unknown. Maturity onset diabetes of youth (MODY) is a form of diabetes mellitus (DM) characterized by fasting hyperglycemia without evidence for autoimmune destruction of beta-cells. METHODS: We genetically analyzed four families of young children with fasting hyperglycemia with family histories of diabetes for mutations in the genes for hepatocyte nuclear factor 4 alpha (HNF4alpha), glucokinase (GCK), and hepatocyte nuclear factor 1 alpha (HNF1alpha), the genes responsible for MODY1, MODY2, and MODY3, respectively. RESULTS: We identified mutations in GCK (Gly258Asp, Arg303Trp, and Arg191Gln) in three of the four families. Molecular genetic characterization in these children clarified the etiology and prognosis of the hyperglycemia and allowed discontinuation of insulin therapy in one family. CONCLUSIONS: We conclude that molecular evaluation for MODY in children with mild fasting hyperglycemia without ketosis with family histories of diabetes can provide important prognostic information to guide therapy and exclude preclinical type 1 diabetes mellitus.