Interdisciplinary care of children with trisomy 13 and 18.

Children with trisomy 13 and 18 (previously deemed "incompatible with life") are living longer, warranting a comprehensive overview of their unique comorbidities and complex care needs. This Review Article provides a summation of the recent literature, informed by the study team's Interdisciplinary Trisomy Translational Program consisting of representatives from: cardiology, cardiothoracic surgery, neonatology, otolaryngology, intensive care, neurology, social work, chaplaincy, nursing, and palliative care. Medical interventions are discussed in the context of decisional-paradigms and whole-family considerations. The communication format, educational endeavors, and lessons learned from the study team's interdisciplinary care processes are shared with recognition of the potential for replication and implementation in other care settings.

Rhenium and technetium complexes of thioamide derivatives of pyridylhydrazine that bind to amyloid-ß plaques.

Age-associated deposition of amyloid-ß in cerebral blood vessels, a condition referred to as cerebral amyloid angiopathy, can contribute to stroke and dementia. This research aimed to design new radioactive technetium-99 m complexes that bind to amyloid-ß plaques that have the potential to assist in diagnosis of cerebral amyloid angiopathy using single-photon-emitted computed tomography (SPECT) imaging. Six new pyridylthiosemicarbazide ligands containing either benzofuran or styrylpyridyl functional groups that are known to selectively bind to amyloid plaques were prepared. Non-radioactive isotopes of technetium are not available so rhenium was used as a surrogate for exploratory chemistry. The new ligands were used to prepare well-defined [Re-oxo]3+ complexes where two pyridylthiosemicarbazide ligands were coordinated to a single metal ion to give bivalent complexes with two amyloid-ß targeting functional groups. The interaction of the [Re-oxo]3+ complexes with synthetic amyloid-ß1-42 and with amyloid plaques in human brain tissue was investigated. Two ligands were selected to develop methods to prepare their [99mTc-oxo]3+ complexes at the tracer level. These technetium-99 m complexes are likely to be isostructural to their rhenium-oxo analogues.

Increased hepatic stiffness as consequence of high hepatic afterload in the Fontan circulation: a vascular Doppler and elastography study.

UNLABELLED: Hepatic dysfunction is a recognized complication after Fontan palliation of congenital heart disease. We sought to quantitatively measure hepatic stiffness and vascular Doppler indices using ultrasound (US) and shear wave elastography (SWE) in a Fontan cohort. Subjects were prospectively recruited for echocardiography and real-time hepatic duplex US with SWE for hepatic stiffness (kPa). Doppler peak velocities, velocity time integral, resistive, pulsatility, acceleration indices (RI, PI, AI), and flow volume were measured in celiac artery, superior mesenteric artery, and main portal vein (MPV). A subset underwent cardiac catheterizations with liver biopsy. Correlations were explored between SWE, duplex, hemodynamic, and histopathologic data. In all, 106 subjects were studied including 41 patients with Fontan physiology (age 13.8 ± 6 years, weight 45.4 ± 23 kg) and 65 controls (age 15.0 ± 8.4 years, weight 47.9 ± 22 kg). Patients with Fontan physiology had significantly higher hepatic stiffness (15.6 versus 5.5 kPa, P < 0.0001), higher celiac RI (0.78 versus 0.73, P = 0.04) superior mesenteric artery RI (0.89 versus 0.84, P = 0.005), and celiac PI (1.87 versus 1.6, P = 0.034); while MPV flow volume (287 versus 420 mL/min in controls, P = 0.007) and SMA AI (829 versus 1100, P = 0.002) were lower. Significant correlation was seen for stiffness with ventricular end-diastolic pressure (P = 0.001) and pulmonary artery wedge pressure (P = 0.009). Greater stiffness correlated with greater degrees of histopathologic fibrosis. No significant change was seen in stiffness or other duplex indices with age, gender, time since Fontan, or ventricular morphology. CONCLUSION: Elevated hepatic afterload in Fontan, manifested by high ventricular end-diastolic pressures and pulmonary arterial wedge pressures, is associated with remarkably increased hepatic stiffness, abnormal vascular flow patterns, and fibrotic histologic changes. The MPV is dilated and carries decreased flow volume, while the celiac and superior mesenteric arterial RI is increased. SWE is feasible in this population and shows promise as a means for predicting disease severity on liver biopsy.

Trajectory to Fellowship: further examination of the road to becoming a psychiatrist.

OBJECTIVES: In 2003 a revised RANZCP training program was implemented. This involved a revised training structure with Basic (years 1-3) and Advanced (years 4-5) requirements. All summative assessments occur during Basic Training and generalist or sub-specialty streams are available in Advanced Training. Trainees that started from2003 onwards have reached or exceeded the minimum time to attain Fellowship. This paper updates the original study to assess the progression of trainees through the elements of the training program and those that have attained Fellowship. METHODS: This paper examines the pathway and barriers to attaining Fellowship with a focus on assessments and time to complete. RESULTS: Data were extracted for all trainees commencing training between December 2003 and February 2006. Items on assessments, rotations, breaks in training, part-time training, and other items were analysed. Time taken to complete mandatory training requirements and outcomes were the key elements evaluated. CONCLUSIONS: For those who attained Fellowship, the median training time was 6.1 years. It was common for trainees to attain Fellowship in the minimum time of 5 years. Delaying the completion of assessments or examinations contributed to the expanded time to attain Fellowship Training, as did part-time training and breaks in training.

Introducing a competency based Fellowship programme for psychiatry in Australia and New Zealand.

OBJECTIVES: The aim of this paper is to summarise the new psychiatry Fellowship programme and its rationale, highlighting the new inclusions, revised assessment structure, the benefits and structure of the programme. CONCLUSIONS: The 2012 Fellowship programme is based on the CanMEDs educational framework. The Royal Australian and New Zealand College of Psychiatrists (RANZCP) underwent a comprehensive process, adapting the CanMEDs competencies to a psychiatric framework and mapping the curriculum to Fellowship competencies, learning outcomes and developmental descriptors of the various stages of training. The 2012 Fellowship programme introduced summative entrustable professional activities (EPAs), formative workplace-based assessments (WBAs) and revised external assessments.

Reflections on training in psychiatry.

OBJECTIVE: There is limited information as to whether graduates from postgraduate specialist medical training programmes in Australia and New Zealand feel prepared for practice, and none regarding the Royal Australian and New Zealand College of Psychiatrists' (RANZCP) training programme. The aims of this study were: to assess the effectiveness of the RANZCP training programme in producing psychiatrists who feel prepared for their roles; and to obtain Fellowship applicants' perceptions of the training programme. METHODS: Applicants for Fellowship (i.e. trainees who had successfully completed RANZCP training) were invited to complete an anonymous online survey that assessed their preparedness for practice and their impressions of the training programme, supervision, training specialties and course content. RESULTS: The response rate was 66% from 101 applicants. Fellowship applicants largely felt prepared for practice and had positive perceptions of the training programme. The majority stated that most of their learning goals were met, but continued training and ongoing learning was required. Areas for improvement included assessments, administration, the balance between service delivery and training, and ongoing training. CONCLUSIONS: Fellowship applicants largely felt confident in their ability to deliver psychiatric services and that the training programme was meeting their needs.

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.

Patent ductus arteriosus closure using the Amplatzer® vascular plug II for all anatomic variants.

OBJECTIVES: To evaluate the safety and efficacy of the Amplatzer® Vascular Plug II (AVPII) for closure of the patent ductus arteriosus (PDA). BACKGROUND: The PDA has significant anatomic variation. No device has proven applicable to all PDAs. Previous case reports and small series have documented limited use of the AVPII for some PDA types. We describe the largest and most diverse experience using the AVPII. METHODS: A retrospective analysis of patients undergoing percutaneous PDA closure between 01/01/2009 and 05/01/2012 was performed. The PDA was characterized, measured, and the device chosen was listed. Deployment technique, complications and procedural results were recorded. RESULTS: Sixty-seven procedures were performed. The AVPII was utilized for 43 (64.2%), 15 (20.9%) had coils, 7 (10.4%) had the AGA duct occluder, and 3 (4.5%) were referred for surgery. The AVPII was placed in infants as young as 2 months and 4.2 kg. AVPII size ranged from 4 to 10 mm. All PDA types were closed. Retrograde and antegrade deployments were performed, using the outer disc as a "retention skirt" to secure the device and improve occlusion. Three patients were up-sized prior to release. All deployments were successful; 89% "in-lab" and 100% closure on postprocedural echocardiogram. There were no complications. CONCLUSIONS: We report the largest experience with the AVPII for PDA closure. The device was used in all morphologic types and small patients. It is low profile, easily repositioned, and had excellent results without complications. We contend that this is the most versatile device currently available.

Trajectory to fellowship: an analysis of the current pathway to becoming a psychiatrist.

OBJECTIVE: This study sought to examine the pathway and barriers to attaining The Royal Australian and New Zealand College of Psychiatrists'(RANZCP) Fellowship for those undergoing the current training program, which was implemented in November 2003. This program involved a new training structure, with basic (years 1-3) and advanced (years 4-5) requirements. All formal assessments occur during Basic Training, while either generalist or sub-specialty streams are available during Advanced Training. We assessed 3 years' intake of trainees who had commenced with the current program and have reached the minimum time to attain RANZCP Fellowship. METHODS: Data were extracted from the College's database for all trainees who commenced training between December 2003 and February 2006; we analysed data on assessments, rotations, breaks in training, part-time status, and other items. The key elements evaluated were the time to complete mandatory training requirements and outcomes. CONCLUSIONS: For those attaining RANZCP Fellowship within this cohort, the median Training time was consistent with the structure of the 5-year training program. It was clear that the RANZCP Fellowship Training Program is flexible, because 43% of the trainees studied undertook periods of part-time training and/or breaks in training, plus a range of sub-speciality programs were commenced in the Advanced Training.

How the rural risk environment underpins hepatitis C risk: Qualitative findings from rural southern Illinois, United States.

BACKGROUND: Hepatitis C virus (HCV) infection has increased among persons who inject drugs (PWID) in the United States with disproportionate burden in rural areas. We use the Risk Environment framework to explore potential economic, physical, social, and political determinants of hepatitis C in rural southern Illinois. METHODS: Nineteen in-depth semi-structured interviews were conducted with PWID from August 2019 through February 2020 (i.e., pre-COVID-19 pandemic) and four with key informants who professionally worked with PWID. Interviews were recorded, professionally transcribed, and coded using qualitative software. We followed a grounded theory approach for coding and analyses. RESULTS: We identify economic, physical, policy, and social factors that may influence HCV transmission risk and serve as barriers to HCV care. Economic instability and lack of economic opportunities, a lack of physically available HCV prevention and treatment services, structural stigma such as policies that criminalize drug use, and social stigma emerged in interviews as potential risks for transmission and barriers to care. CONCLUSION: The rural risk environment framework acknowledges the importance of community and structural factors that influence HCV infection and other disease transmission and care. We find that larger structural factors produce vulnerabilities and reduce access to resources, which negatively impact hepatitis C disease outcomes.

I Don't Believe a Person Has to Die When Trying to Get High: Overdose Prevention and Response Strategies in Rural Illinois.

BACKGROUND: Overdose is a leading cause of morbidity and mortality among people who inject drugs. Illicitly manufactured fentanyl is now a major driver of opioid overdose deaths. METHODS: Semi-structured interviews were conducted with 23 participants (19 persons who inject drugs and 4 service providers) from rural southern Illinois. Data were analyzed using constant comparison and theoretical sampling methods. RESULTS: Participants were concerned about the growing presence of fentanyl in both opioids and stimulants, and many disclosed overdose experiences. Strategies participants reported using to lower overdose risk included purchasing drugs from trusted sellers and modifying drug use practices by partially injecting and/or changing the route of transmission. Approximately half of persons who inject drugs sampled had heard of fentanyl test strips, however fentanyl test strip use was low. To reverse overdoses, participants reported using cold water baths. Use of naloxone to reverse overdose was low. Barriers to naloxone access and use included fear of arrest and opioid withdrawal. CONCLUSIONS: People who inject drugs understood fentanyl to be a potential contaminant in their drug supply and actively engaged in harm reduction techniques to try to prevent overdose. Interventions to increase harm reduction education and information about and access to fentanyl test strips and naloxone would be beneficial.

Safety of cardiac magnetic resonance and contrast angiography for neonates and small infants: a 10-year single-institution experience.

BACKGROUND: With increasing applications of cardiac magnetic resonance (CMR) and magnetic resonance angiography (MRA) for evaluation of congenital heart disease (CHD), safety of this technology in the very young is of particular interest. OBJECTIVE: We report our 10-year experience with CMR in neonates and small infants with particular focus on the safety profile and incidence of adverse events (AEs). MATERIALS AND METHODS: We reviewed clinical, anesthesia and nursing records of all children ≤120 days of age who underwent CMR. We recorded variables including cardiac diagnosis, study duration, anesthesia type and agents, prostaglandin E1 (PGE1) dependence and gadolinium (Gd) use. Serially recorded temperature, systemic saturation (SpO(2)) and cardiac rhythm were analyzed. Primary outcome measure was any AE during or <24 h after the procedure, including minor AEs such as hypothermia (axillary temperature ≤95 °F), desaturation (SpO(2) drop ≥10% below baseline) and bradycardia (heart rate ≤100 bpm). Secondary outcome measure was unplanned overnight hospitalization of outpatients. RESULTS: Children (n = 143; 74 boys, 69 girls) had a median age of 6 days (1-117), and 98 were ≤30 days at the time of CMR. The median weight was 3.4 kg (1.4-6 kg) and body surface area 0.22 m(2) (0.13-0.32 m(2)). There were 118 (83%) inpatients (108 receiving intensive care) and 25 (17%) outpatients. Indications for CMR were assessment of aortic arch (n = 57), complex CHD (n = 41), pulmonary veins (n = 15), vascular ring (n = 8), intracardiac mass (n = 8), pulmonary artery (n = 7), ventricular volume (n = 4), and systemic veins (n = 3). CMR was performed using a 1.5-T scanner and a commercially available coil. CMR utilized general anesthesia (GA) in 86 children, deep sedation (DS) in 50 and comforting methods in seven. MRA was performed in 136 children. Fifty-nine children were PGE1-dependent and 39 had single-ventricle circulation. Among children on PGE1, 43 (73%) had GA and 10 (17%) had DS. Twelve children (9%) had adverse events (AEs)-one major and 11 minor. Of those 12, nine children had GA (10%) and three had DS (6%). The single major AE was respiratory arrest after DS in a neonate (resuscitated without sequelae). Minor AEs included desaturations (n = 2), hypothermia (n = 5), bradycardia (n = 2), and bradycardia with hypoxemia (n = 2). Incidence of minor AEs was 9% for inpatients (vs. 4% for outpatients), and 8% for neonates (vs. 9% for age ≥30 days). Incidence of minor AEs was similar between PGE1-dependent infants and the non-PGE1 group. There were no adverse events related to MRA. Of 25 outpatients, 5 (20%) were admitted for overnight observation due to desaturations. CONCLUSION: CMR and MRA can be accomplished safely in neonates and infants ≤120 days old for a wide range of pre-surgical cardiac indications. Adverse events were unrelated to patient age, complexity of heart disease, type of anesthesia or PGE1 dependence.

Structural and community changes during COVID-19 and their effects on overdose precursors among rural people who use drugs: a mixed-methods analysis.

BACKGROUND: Drug overdose rates in the United States have been steadily increasing, particularly in rural areas. The COVID-19 pandemic and associated mitigation strategies may have increased overdose risk for people who use drugs by impacting social, community, and structural factors. METHODS: The study included a quantitative survey focused on COVID-19 administered to 50 people who use drugs and semi-structured qualitative interviews with 17 people who use drugs, 12 of whom also participated in the quantitative survey. Descriptive statistics were run for the quantitative data. Qualitative coding was line-by-line then grouped thematically. Quantitative and qualitative data were integrated during analysis. RESULTS: Findings demonstrate how COVID-19 disruptions at the structural and community level affected outcomes related to mental health and drug use at the individual level. Themes that emerged from the qualitative interviews were (1) lack of employment opportunities, (2) food and housing insecurity, (3) community stigma impacting health service use, (4) mental health strains, and (5) drug market disruptions. Structural and community changes increased anxiety, depression, and loneliness on the individual level, as well as changes in drug use patterns, all of which are likely to increase overdose risk. CONCLUSION: The COVID-19 pandemic, and mitigation strategies aimed at curbing infection, disrupted communities and lives of people who use drugs. These disruptions altered individual drug use and mental health outcomes, which could increase risk for overdose. We recommend addressing structural and community factors, including developing multi-level interventions, to combat overdose. Trial registration Clinicaltrails.gov: NCT04427202. Registered June 11, 2020: https://clinicaltrials.gov/ct2/show/NCT04427202?term=pho+mai&draw=2&rank=3.

The Impact of the COVID-19 Pandemic on Drug Use Behaviors, Fentanyl Exposure, and Harm Reduction Service Support among People Who Use Drugs in Rural Settings.

BACKGROUND: The COVID-19 pandemic has worsened the opioid overdose crisis in the US. Rural communities have been disproportionately affected by opioid use and people who use drugs in these settings may be acutely vulnerable to pandemic-related disruptions due to high rates of poverty, social isolation, and pervasive resource limitations. METHODS: We performed a mixed-methods study to assess the impact of the pandemic in a convenience sample of people who use drugs in rural Illinois. We conducted 50 surveys capturing demographics, drug availability, drug use, sharing practices, and mental health symptoms. In total, 19 qualitative interviews were performed to further explore COVID-19 knowledge, impact on personal and community life, drug acquisition and use, overdose, and protective substance use adaptations. RESULTS: Drug use increased during the pandemic, including the use of fentanyl products such as gel encapsulated "beans" and "buttons". Disruptions in supply, including the decreased availability of heroin, increased methamphetamine costs and a concomitant rise in local methamphetamine production, and possible fentanyl contamination of methamphetamine was reported. Participants reported increased drug use alone, experience and/or witness of overdose, depression, anxiety, and loneliness. Consistent access to harm reduction services, including naloxone and fentanyl test strips, was highlighted as a source of hope and community resiliency. CONCLUSIONS: The COVID-19 pandemic period was characterized by changing drug availability, increased overdose risk, and other drug-related harms faced by people who use drugs in rural areas. Our findings emphasize the importance of ensuring access to harm reduction services, including overdose prevention and drug checking for this vulnerable population.

Interruption of the Ascending Aorta-Biventricular Surgical Repair.

Interruption of the ascending aorta is an extremely rare anomaly defined by a point of interruption between the intrapericardial and extrapericardial aorta and can be explained by developmental errors proximal to the embryologic right aortic sac. Herein, we present a case of interruption of the ascending aorta and describe a successful biventricular surgical repair of this unique anomaly.

Increased Hepatic Stiffness in Young Adults After Biventricular Repair of Congenital Heart Disease.

BACKGROUND: This study evaluated hepatic stiffness by shear wave elastography to investigate subclinical hepatic changes in a cohort of patients with congenital biventricular heart disease (BHD). METHODS: The BHD patients and age-matched healthy controls were prospectively recruited for hepatic ultrasonography and shear wave elastography. Real-time B-mode imaging with Doppler was performed for celiac axis, superior mesenteric artery, and main portal vein, and hepatic shear wave elastography was assessed. Vascular Doppler indices included peak velocities; velocity time integral, resistive, pulsatility, and acceleration indices; and portal vein volumetric flow. One-way analysis of variance was used for comparisons between controls, BHD, and a cohort of Glenn and Fontan patients. RESULTS: In all, 66 subjects were included. Thirty-six subjects were in the BHD group (male, 25; female, 11; mean age 27.4 ± 4.6 years; mean weight 76.8 ± 18.5 kg), and 30 were healthy controls (male, 11; female, 23, mean age 27.4 ± 3.8 years; mean weight 70 ± 17.2 kg). Shear wave elastography was increased in BHD (8.11 ± 2.07 kPa) compared with controls (5.44 ± 1.18 kPa; P < .001). Hepatic stiffness in BHD was significantly different from that in the Fontan cohort but not in the infant Glenn cohort. CONCLUSIONS: Increased hepatic stiffness was observed in young adults with repaired BHD. Although cause is not established, possibilities include hepatic congestion early in life or elevated central venous pressures due to right heart burden. Further research is required to determine whether these patients will ultimately have clinically relevant liver disease.

Pulmonary-to-Systemic Arterial Shunt to Treat Children With Severe Pulmonary Hypertension.

BACKGROUND: The placement of a pulmonary-to-systemic arterial shunt in children with severe pulmonary hypertension (PH) has been demonstrated, in relatively small studies, to be an effective palliation for their disease. OBJECTIVES: The aim of this study was to expand upon these earlier findings using an international registry for children with PH who have undergone a shunt procedure. METHODS: Retrospective data were obtained from 110 children with PH who underwent a shunt procedure collected from 13 institutions in Europe and the United States. RESULTS: Seventeen children died in-hospital postprocedure (15%). Of the 93 children successfully discharged home, 18 subsequently died or underwent lung transplantation (20%); the mean follow-up was 3.1 years (range: 25 days to 17 years). The overall 1- and 5-year freedom from death or transplant rates were 77% and 58%, respectively, and 92% and 68% for those discharged home, respectively. Children discharged home had significantly improved World Health Organization functional class (P < 0.001), 6-minute walk distances (P = 0.047) and lower brain natriuretic peptide levels (P < 0.001). Postprocedure, 59% of children were weaned completely from their prostacyclin infusion (P < 0.001). Preprocedural risk factors for dying in-hospital postprocedure included intensive care unit admission (hazard ratio [HR]: 3.2; P = 0.02), mechanical ventilation (HR: 8.3; P < 0.001) and extracorporeal membrane oxygenation (HR: 10.7; P < 0.001). CONCLUSIONS: A pulmonary-to-systemic arterial shunt can provide a child with severe PH significant clinical improvement that is both durable and potentially free from continuous prostacyclin infusion. Five-year survival is comparable to children undergoing lung transplantation for PH. Children with severely decompensated disease requiring aggressive intensive care are not good candidates for the shunt procedure.

Is combined atrial volumetrics by two-dimensional echocardiography a suitable measure for quantitative assessment of the hemodynamic significance of patent ductus arteriosus in neonates and infants?

BACKGROUND: Patent ductus arteriosus (PDA) is a common cardiac problem in neonates and infants, but determination of its hemodynamic significance can be challenging. We hypothesized that combined left (LA) and right atrial (RA) volumes physiologically best reflect hemodynamically significant patent ductus arteriosus (HSPDA), and utilized two-dimensional echocardiography (2DE) derived atrial volumes to test this hypothesis. METHODS: 2DE examinations with good-quality images in 138 neonates <3 months corrected gestational age with PDA, and 50 normal neonates without PDA were selected. Measurements of LA, RA, and combined atrial volumes were performed, in addition to transductal diameters, left atrial to aortic dimension (LA:Ao), and left ventricular end-diastolic to aortic dimension ratios. An experienced cardiologist, blinded to 2DE images of atria and ventricles and to the above measurements, independently assessed HSPDA based only on images and Doppler data of the ductus itself, thus identifying each PDA as of low hemodynamic significance or HSPDA. RESULTS: Receiver operating characteristic (ROC) curves showed indexed LA volumes and LA/RA volume ratios to have moderate power to discriminate HSPDA from low hemodynamic burden PDA. Classic LA:Ao ratio, combined atrial volumes, and RA volumes yielded ROC areas that appeared less promising as discriminators for HSPDA. CONCLUSION: Atrial volume measurements in neonates and infants have a linear association with body surface area and show acceptable inter- and intraobserver agreement. Indexed LA volume and LA/RA volume ratio are potentially useful markers for HSPDA. RA dilation due to left to right shunting through the patent foramen ovale as quantified by RA volume measurements does not appear to be an important marker for HSPDA.

Loss of the PTCH1 gene locus in cardiac fibroma.

BACKGROUND: Cardiac fibroma (CF) is a rare benign tumor that is poorly characterized genetically. CF is more commonly encountered in patients with Gorlin syndrome (3%) than the general population. Mutations of the tumor suppressor gene PTCH1 are the underlying cause of Gorlin syndrome. METHODS: Conventional cytogenetic analysis was performed on a peripheral blood and a CF sample from a 2-week-old male. In addition, fluorescence in situ hybridization (FISH) studies were performed to assess the copy number of the PTCH1 gene locus (9q22.3) on metaphase and interphase cells from these same specimens using yeast artificial protein (YAC) probe 891G1 and on representative paraffin-embedded tissue sections of two additional CFs (one arising in a 2-month-old female and the other in a 13-week-old male). None of the patients had Gorlin syndrome. RESULTS: Karyotypically, the following abnormal chromosomal complement was detected in the 2-week-old male's CF: 46,XY,del(9)(q22q34)[15]. FISH studies revealed homozygous loss of the PTCH1 locus in the cytogenetically analyzed CF and in the CF arising in the 13-week-old male. Heterozygous loss of this locus was identified in the remaining CF from the 2-month-old female. A mutational mechanism other than deletion may be responsible for PTCH1 inactivation on the other locus in this latter patient. Conventional cytogenetic and FISH studies of the peripheral blood sample from the 2-week-old male were normal. CONCLUSION: These data support a tumor suppressor gene role for PTCH1 in nonsyndromic or sporadic CFs.