Evaluation fetal heart in the first and second trimester: Results and limitations.

Background: Cardiac heart defects affect nearly 6-12 per 1000 live births in the general population and are more frequent than common trisomies. Aim: To assess the efficacy and technical limitations of first-trimester fetal heart evaluation in the 11-14th-weeks' scan and comparison with the second-trimester anatomical exam by ultrasound. Material and Method: Between April 2015 and July 2020, medical records and ultrasound data of 3295 pregnancies who underwent first-trimester fetal anatomy exams by ultrasound were reviewed retrospectively. All ultrasound exams were performed by the same two operators (TUKD, OP) with transabdominal transducers. Fetal situs, four-chamber view, outflow tracts, and three-vessel trachea view are the cornerstones of first-trimester fetal heart examination. Conventional grayscale mode and high-definition power Doppler mode were utilized. The same operators re-examined all cases between the 18 and 23 weeks of gestation by ISUOG guidelines. Results: We performed a combined transvaginal and transabdominal approach for only 101 cases (3.06%). The mean maternal age was 31.28 ± 4.43, the median gestational age at the first-trimester ultrasound exam was 12.4 weeks, and the median CRL was 61.87 mm (range was 45.1-84 mm). Even combined approach situs, cardiac axis, and four-chamber view could not be visualized optimally in 28 cases (0.7%). Outflow tracts were visualized separately in 80% (2636 in 3295) cases. Three vessel-trachea views were obtained in 85.4% (2814 in 3295) cases by high-definition Doppler mode. There were 47 fetuses with cardiac defects in 3295 pregnancies with the known pregnancy outcome. Ten cases had abnormal karyotype results. Thirty-two fetuses with cardiac anomalies (9.7 in 1000 pregnancies) were detected in the first-trimester examination, and the remaining 15 (4.55 in 1000 pregnancies) cases were diagnosed in the second-trimester examination. The prevalence of congenital cardiac anomalies was 14.25 in 1000 pregnancies. Fifteen cases were missed in the first-trimester exam. Also, ten fetuses which had abnormal cardiac findings in the first-trimester exam were not confirmed in the second-trimester exam. Sensitivity, specificity, positive, and negative predictive values were calculated as 65.3%, 99.7%, 66.8%, and 99.67%, respectively. Conclusion: Late first-trimester examination of the fetus is feasible and allows earlier detection of many structural abnormalities of the fetus, including congenital heart defects. Suspicious and isolated cardiac abnormal findings should be re-examined and confirmed in the second-trimester exam. Previous abdominal surgery, high BMI, and subtle cardiac defects can cause missed cardiac abnormalities.

Current perspectives on systemic hypertension in heart failure with preserved ejection fraction.

Hypertension is a major contributor to the development of heart failure with preserved ejection fraction (HFpEF). Our understanding of the epidemiology and pathophysiology of HFpEF in relation to hypertension has increased considerably in recent years. We now know that the pathophysiologic relationship between hypertension and HFpEF is more complex than simply the development of left ventricular hypertrophy and diastolic dysfunction and that there are multiple ways in which hypertension interacts with other comorbidities, the vasculature, and the heart to predispose to HFpEF. Although the treatment of HFpEF has been challenging, there is widespread agreement that control of systemic blood pressure is important in the management of these patients. Here we review the relationship between hypertension and HFpEF, focusing on (1) epidemiology and (2) pathophysiology of HFpEF in relation to hypertension; (3) prevention of HFpEF by controlling hypertension; and (4) established and novel therapeutics for hypertension in the setting of HFpEF.

A case of Seckel syndrome with tricuspid atresia.

Seckel syndrome is an autosomal recessive disease presenting with marked growth retardation, microcephalic dwarfism, some facial and skeletal abnormalities. Tricuspid atresia is a rare and life threatening cyanotic congenital heart diseases, with an incidence of 1% to 3%. It is feature of the anatomically normally related great arteries with a large ventricular septum defect and stenosis of right ventricular outflow tract. Tricuspid atresia has never been reported in patients with Seckel syndrome. Here we report a 15-day-old girl baby diagnosed as having Seckel syndrome with tricuspid atresia.

Extreme externalisation of a Riata defibrillator lead conductor cable with prolapse into the left pulmonary artery.

The Riata family of defibrillator leads (St. Jude Medical, Sylmar, CA) has been recalled because of externalisation of conductor cables and increased electrical failure. We describe the case of a man with an incidental finding of extreme externalisation of a conductor from the right ventricular defibrillator lead (Riata family) with prolapse into the left pulmonary artery.

The emerging epidemic of heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF), which currently represents approximately 50 % of heart failure (HF) cases, is common and associated with high morbidity and mortality. Understanding the epidemiology of HFpEF has been difficult due to the challenges in HFpEF diagnosis and the heterogeneous etiologies and pathophysiologies that underlie HFpEF. Nevertheless, several high-quality epidemiology and observational registry studies of HFpEF demonstrate that an increasing prevalence of HFpEF in both the outpatient and inpatient settings, coupled with a lack of evidence-based effective treatments for HFpEF, is resulting in an emerging epidemic of HFpEF. In this review, we discuss the emerging HFpEF epidemic, focusing on: (1) reasons for the rising prevalence of HFpEF; (2) the abnormalities in cardiac structure and function that dictate the transition from risk factors to HFpEF; (3) novel HFpEF mechanisms that may underlie the increase in HFpEF prevalence; (4) prognosis of HFpEF; and (5) risk prediction in HFpEF. We conclude with 10 unanswered questions onHFpEF epidemiology thatwill be important areas for future investigation.

Screening for metastasis in primary breast cancer patients having four or more axillary lymph node involvement: is it really necessary?

PURPOSE: To evaluate the necessity and direct cost effectiveness of screening and staging procedures in breast cancer patients having ≥4 positive axillary lymph nodes and to identify further possible biopathological risk factors associated with increased risk of metastasis. METHODS: We reviewed the demographic and clinicopathological data from the medical records of 1897 newly diagnosed breast cancer patients. Patients having ≥4 positive axillary lymph nodes after primary surgery for breast cancer and who had staging examinations for metastasis were eligible. The impact of staging procedures (thoracoabdominal CT, bone scan etc.) for detecting metastasis, decision of adjuvant treatment and direct costs were analyzed in 329 patients with operable breast cancer. RESULTS: Thirty-five (10.6%) patients were found with metastasis at diagnosis. Seven (20.0%) among them had multiple metastases. Eighteen (51.4%) had lung, 17 (48.6%) bone, and 7 (20.0%) liver metastasis. Twenty-one (60.0%) patients needed further radiological investigation for metastasis confirmation. Treatment decision was changed in 27 (77.1%) patients. No statistically significant risk factor was identified among the metastatic patients by means of conventional demographic and biopathological parameters. The cost of screening was lower when compared to the cost of treatment without any screening procedure. CONCLUSION: Since the conventional clinicopathological data seems not sufficient to define the risk of developing metastasis in breast cancer patients with ≥4 axillary lymph node involvement, all of them should undergo full staging examinations until new parameters based on genomic level are defined. Staging procedures need modification for high risk breast cancer patients.

Radioisotope synovectomy with rhenium186 in haemophilic synovitis for elbows, ankles and shoulders.

We have performed 221 radioisotope synovectomy (RS) in more than 150 children and young adults with haemophilia, age ranging 3-30 years (mean 15) in Ege Hemophilia Center, Izmir, Turkey for last 7 years. We always preferred to use Yttrium 90 (Y(90)) for knees; however, since 2005, we started using rhenium 186 (Re(186)) for medium-sized joints with respect to safety. In this article, we have evaluated long-term experience ranging from 6 months to 3 years (mean 18 months) with Re(186) for elbows (n = 35), ankles (n = 26) and shoulders (n = 2) in total of 63 RS procedures for 49 patients. Their age range was 3-30 years and mean age was 15.5. Two mCi of Re(186) intra-articularly injected for treating target joints and chronical synovitis. After RS, joint bleedings were decreased for all patients. The best results were obtained for all joints in patients with grade-II synovitis as like earlier experience with Y(90). Excellent rates (no bleeding) were observed in grade-II synovitis in 81% and 46% for elbows vs. 86% and 57% for ankles after 6 months and after 1 year follow-up of patients, respectively. In grade-III synovitis, excellent rates were 53% and 25% for elbows and 44% and 29% for ankles, respectively. In five joints for five patients, repeated injections were needed for better outcome. No adverse events such as radioisotope leakage, local inflamatory reactions or malignancy development were observed during and after RS. For medium-sized joints, RS with Re(186) seems to be either effective or safe treatment method. Our results confirm those previously published by others on the value of Re(186) synoviorthesis in medium-sized joints in haemophilia patients. After this experience, we changed our protocol and we use Re(186) for all medium-sized joints for treating chronical synovitis.

Diagnosis and management of heart failure with preserved ejection fraction: 10 key lessons.

Heart failure with preserved ejection fraction (HFpEF) is a common clinical syndrome associated with high rates of morbidity and mortality. Due to the lack of evidence-based therapies and increasing prevalence of HFpEF, clinicians are often confronted with these patients and yet have little guidance on how to effectively diagnose and manage them. Here we offer 10 key lessons to assist with the care of patients with HFpEF: (1) Know the difference between diastolic dysfunction, diastolic heart failure, and HFpEF; (2) diagnosing HFpEF is challenging, so be thorough and consider invasive hemodynamic testing to confirm the diagnosis; (3) a normal B-type natriuretic peptide does not exclude the diagnosis of HFpEF; (4) elevated pulmonary artery systolic pressure on echocardiography in the presence of a normal ejection fraction should prompt consideration of HFpEF; (5) use dynamic testing in evaluating the possibility of HFpEF in patients with unexplained dyspnea or exercise tolerance; (6) all patients with HFpEF should be systematically evaluated for the presence of coronary artery disease; (7) use targeted treatment for HFpEF patients based on their phenotypic classification; (8) treat HFpEF patients now by treating their comorbidities; (9) understand the importance of heart rate in HFpEF- lower is not always better; and (10) do not forget to consider rare diseases ("zebras") as causes for HFpEF when evaluating and treating patients. Taken together, these 10 key lessons can help clinicians care for challenging patients with HFpEF while we eagerly await the results of ongoing HFpEF clinical trials and observational studies.

Sinus pause in association with Lyme carditis.

Lyme disease is the most prevalent tick-borne disease in the United States. It is caused by the spirochete Borrelia burgdorferi. Cardiac involvement is seen in 4% to 10% of patients with Lyme disease. The principal manifestation of Lyme carditis is self-limited conduction system disease, with predominant involvement of the atrioventricular node. On rare occasions, Lyme carditis patients present with other conduction system disorders such as bundle branch block, intraventricular conduction delay, and supraventricular or ventricular tachycardia. We report the unusual case of a 59-year-old man who presented with new-onset symptomatic sinus pauses one month after hiking in upstate New York. To our knowledge, this is the first case report from North America that describes the relationship between symptomatic sinus pause and Lyme carditis.

Association between salt sensitivity and target organ damage in essential hypertension.

Cardiovascular events occur more frequently in sodium-sensitive patients with essential hypertension; recently, sodium sensitivity was shown to be a cardiovascular risk factor independently of other classic factors such as blood pressure and cigarette smoking This study examined the relationship between salt sensitivity status and target organ damage in hypertensive patients. Ninety-six patients (35 men, 61 women) with moderate essential hypertension were studied for salt sensitivity status and the presence of target organ damage, including hypertensive retinopathy, serum creatinine, creatinine clearance, and urinary albumin excretion (UAE). Four different patterns of left ventricular anatomic adaptation were identified by categorizing patients according to the values of left ventricular mass index and relative wall thickness by the means of echocardiography. Forty-five (47%) patients were shown to be salt-sensitive, in contrast to 51 (53%) salt-resistant subjects. Serum creatinine and UAE were significantly higher in the group of salt-sensitive hypertensives (P < .05 and P < .001, respectively). Left ventricular mass index (LVMI), relative wall thickness (RWT), and left atrial index (LAI) were all significantly higher in the group of salt-sensitive hypertensive patients. Concentric hypertrophy was significantly more prevalent in the salt-sensitive group (37.8% v 11.8%; P < .01). The prevalence of hypertensive retinopathy in the salt-sensitive group was 84.4%, in contrast to 59.6% in the salt-resistant group (P < .01). Multivariate regression analysis revealed salt sensitivity as a significant predictor of LVMI, RWT, and UAE, independently of age, body mass index, and mean blood pressure. In conclusion, salt-sensitive hypertensive patients are more prone to develop severe hypertensive target organ damage that may enhance their risk of renal and cardiovascular morbidity.

An unusual native tricuspid valve endocarditis caused by Candida colliculosa.

Candida colliculosa, which grew in blood cultures of a 71-year-old retired man with fever of unknown origin that had lasted for 7 months, in conjunction with transthoracic echocardiography, demonstrating a 20-mm vegetation, superior to the tricuspid valve, herniating into the right atrial cavity. The finding led to the diagnosis of fungal endocarditis. Fluconazole, 600 mg daily, was commenced for 8 days; followed by amphotericin B, 1 mg/kg daily. On the fourth day of the amphotericin B treatment, the patient underwent replacement of the infected tricuspid valve. Even though the initial postoperative period was relatively uncomplicated, the patient died after a gross aspiration on the 67th day of his hospital stay, despite aggressive cardiovascular support and antimicrobial therapy. This is the first report of a native tricuspid valve fungal endocarditis due to C. colliculosa or Torulaspora delbrueckii, which is not known to be a human pathogen.

Effects of a single dose of oral estrogen on left ventricular diastolic function in hypertensive postmenopausal women with diastolic dysfunction.

OBJECTIVE: To evaluate the acute effects of a single dose of oral estrogen on left ventricular diastolic function in hypertensive postmenopausal women with diastolic dysfunction. DESIGN: Prospective, double-blind, placebo-controlled, clinical study. SETTING: Cardiology and postmenopausal outpatient clinics of a university hospital. PATIENT(S): Thirty postmenopausal women with hypertension (diastolic blood pressure of >90 mm Hg) and left ventricular diastolic dysfunction (mitral E/A ratio [the ratio of peak velocity of early mitral diastolic filling to late diastolic filling] of <1 and isovolumic relaxation time of >100 ms) were included in the study. Thirty normotensive postmenopausal women with normal left ventricular diastolic function served as the control group. INTERVENTION(S): Conjugated equine estrogen (0.625 mg) was given orally. Left ventricular diastolic function was assessed by Doppler echocardiography at baseline and 3 hours after the administration of estrogen. MAIN OUTCOME MEASURE(S): Left ventricular diastolic filling as assessed by Doppler echocardiography. RESULT(S): Estrogen had no effect on heart rate or blood pressure in either study group. The baseline E/A ratios were 0.72 +/- 0.26 and 1.22 +/- 0.30, and the isovolumic relaxation times were 122 +/- 18 ms and 89 +/-14 ms in the hypertensive and normotensive groups, respectively. Estrogen had no significant effect on any of the Doppler parameters in the normotensive group. In the hypertensive group, there was a trend toward normalization of the E/A ratio (from 0.73 +/- 0.11 to 0.84 +/- 20) and a significant improvement in the isovolumic relaxation time (from 124 +/- 20 ms to 105 +/- 13 ms) in response to the administration of estrogen compared with placebo. CONCLUSION(S): A single dose of oral estrogen caused a significant improvement in left ventricular diastolic filling in hypertensive postmenopausal women with diastolic dysfunction.

Night-time blood pressure load is associated with higher left ventricular mass index in renal transplant recipients.

The absence of nocturnal fall in blood pressure (BP) is named as nondipper status, which has been shown to be an additional risk factor for the development of left ventricular hypertrophy and cardiovascular events in several high-risk groups. The aim of this study was to determine the influences of the nondipper status and nocturnal blood pressure loads on left ventricular mass index (LVMI) in renal transplant recipients. A total of 35 nondiabetic renal transplant recipients were included into the study. A 24-h ambulatory blood pressure monitoring (ABPM) was performed for all recipients. The nondipper status was defined as either an increase in night-time mean arterial pressure (MAP) or a decrease of no more than 10% of daytime MAP. LVMI was measured by using two-dimensional guided M-mode echocardiography. The night-time systolic blood pressure (SBP) load was defined as the percentage of the time, during which SBP exceeded 125 mmHg during night time. The nondipping was common among renal transplant recipients, of whom 60% were nondipper in our study. LVMI was significantly higher in the nondipper group vs the dipper group (133 +/- 35 g/m(2) vs 109 +/- 26 g/m(2), P = 0.04). A fall in MAP at night time was 14.5 +/- 4.3% in the dipper group, while it was 1.4 +/- 6.1% in the nondipper group (P < 0.001). On stepwise multiple regression analysis, night-time SBP load and haemoglobin were independent predictors of LVMI (R(2) = 0.53). In conclusion, nondipping is common after renal transplantation. Night-time SBP load and low haemoglobin are closely related to the increase in LVMI in renal transplant recipients. ABPM may be a more useful tool in optimizing treatment strategies to reduce cardio-vascular events in renal transplant recipients.

Measurement of myocardial fractional flow reserve during coronary angioplasty in infarct-related and non-infarct related coronary artery lesions.

Myocardial fractional flow reserve (FFRmyo) has been demonstrated to be a useful method for determining the physiologic importance of a given coronary lesion. However, the reliability of the FFRmyo measurement is unknown in infarct-related arteries (IRA). The aim of this study was to measure and correlate the FFRmyo results of 14 consecutive patients who had recent acute myocardial infarction (AMI) (Group 1) with 14 consecutive patients who didnOt have AMI (Group 2) before and after percutaneous transluminal coronary angioplasty (PTCA). Quantitative coronary angiography (QCA) and FFRmyo measurements were determined both before and after optimal PTCA for all patients. FFRmyo was measured by use of a 0.014 inch guidewire as the ratio of the pressure distal to the target lesion to the aortic pressure taken during the maximal hyperemia induced by intracoronary adenosine. There were no differences between the two groups related to gender, target artery reference diameter, minimal luminal diameter and percent diameter stenosis of the vessel both before and after PTCA. While FFRmyo results after PTCA were not different between the groups, they were statistically different before PTCA (Group 1: 77.6+/-5.4%, Group 2: 63.3+/-8.4%; p<0.001). Although QCA-determined percent diameter stenosis revealed a significant degree of stenosis (66.5+/-10.5%) for Group 1, FFRmyo values were higher than 75% (77.6+/-5.4%), indicating insignificant stenosis. Thus, it was concluded that FFRmyo measurements before PTCA were significantly different between IRA and non-IRA and that the method may not be valid for the determination of stenosis significance in IRA.

Correlation of myocardial fractional flow reserve with thallium-201 SPECT imaging in intermediate-severity coronary artery lesions.

PURPOSE: The purpose of this study was to compare the measurements of fractional flow reserve of the myocardium (FFRmyo) with results of quantitative coronary angiography (QCA) and stress single-photon emission computed tomography thallium-201 (SPECT 201Tl) imaging in patients with intermediate-severity coronary artery disease (ISCAD). METHODS: We prospectively evaluated 40 lesions of QCA-determined ISCAD in 30 patients (age, 53.3 +/- 10.2 years; 67% male) using a 0. 014 inch pressure wire during elective coronary angiography and compared the results with those of SPECT 201Tl performed within a week of angiography. RESULTS: There was a moderate negative correlation between percent diameter stenosis (%DS) and FFRmyo (53.1 +/- 13.4% and 0.75 +/- 0.09, respectively; r = -0.40; p = 0.01). Twenty-two out of 40 vascular territories (55%) were found to have perfusion defects (Group 1) and 18 territories (45%) were found to be normal (Group 2). While QCA-determined stenosis severity was not different between Group 1 and Group 2 (56 +/- 12% vs. 50 +/- 16%, respectively; p = 0.3), FFRmyo was found to be significantly different between the two groups (0.68 +/- 0.05 vs. 0.83 +/- 0.05, respectively; p = 0.001). When %DS and FFRmyo results were dichotomized as abnormal by 50% and < 0.75, respectively, and SPECT 201Tl was taken as the gold standard, sensitivity, specificity, positive predictive value and negative predictive value of %DS and FFRmyo were 0.55 vs. 0.91, 0.56 vs. 1.0, 0.60 vs. 1.0 and 0.50 vs. 0. 90, respectively. CONCLUSION: While FFRmyo seems to accurately predict the presence of ischemia on SPECT 201Tl in patients with ISCAD, QCA does not reliably assess the physiologic impact of the same lesions.

Mad honey poisoning in man and rat.

Grayanotoxins are known to occur in the honey produced from the nectar of Rhododendron ponticum growing on the mountains of the eastern Black Sea region of Turkey and also in Japan, Nepal, Brazil, and some parts of North America and Europe. Two cases of honey intoxication are presented here. Both of the patients experienced severe bradycardia and hypotension after ingestion of honey which was brought from Trabzon, Turkey. Microscopical examination showed Rhododendron ponticum pollen tetrades. Anesthetized albino rats were injected intraperitoneally with toxic honey extract doses equivalent to 1 or 5 g honey/kg. Dose-dependent hypotension, bradycardia and respiratory rate depression were observed. When marked bradycardia (approximately 75% of control value) was reached, rats were given atropine sulfate (2 mg/kg, i.p.) or AF-DX 116 (20 mg/kg, i.p.). Atropine sulfate improved both bradycardia and respiratory rate depression. AF-DX 116, which is a selective M2-muscarinic receptor antagonist, restored only heart rate, but not the respiratory rate depression. These results suggest that M2-muscarinic receptors are involved in cardiotoxicity of grayanotoxin.

Tc-99m sestamibi gated SPECT in patients with left bundle branch block.

PURPOSE: The purpose of this study was to assess the diagnostic role of a Tc-99m sestamibi gated SPECT technique in patients with left bundle branch block (LBBB) without known coronary artery disease. MATERIALS AND METHODS: Twenty consecutive patients with constant complete LBBB were included. A same-day rest-stress protocol was used, and dipyridamole stress (14 patients) or treadmill exercise (6 patients) was applied. Electrocardiograph (ECG)-gated SPECT images were acquired 15 minutes after the administration of 0.31 mCi/kg Tc-99m sestamibi at peak stress. Regional myocardial perfusion was analyzed in relation to the cardiac cycle. RESULTS: Eleven of 14 patients who underwent a dipyridamole stress test had hypoactivity in the left anterior descending (LAD) artery territory in the ungated (summed) stress-rest images (abnormality ratio, 78%). On the ungated images, the abnormality was completely reversible in one patient (9%), partially reversible in five patients (46%), irreversible in two patients (18%), and reverse perfusion was identified in three patients (27%). Abnormality ratios of end-systolic and end-diastolic data were 93% and 29%, respectively. Conversely, the ungated rest-stress and end-systolic images of all the patients who performed treadmill exercise were abnormal despite the presence of normal or nearly normal end-diastolic myocardial perfusion. The angiographic findings correlated best with those of end-diastolic images. In 13 patients without coronary artery disease, normal or nearly normal regional perfusion was observed on end-diastole, but four patients with abnormal end-diastolic perfusion, which involved the LAD territory in all but one, had substantial coronary artery disease. The number of the involved segments was similar on the end-systolic and ungated data. Most of these artifactual defects were localized to the anteroseptal, septal, and inferoseptal segments. CONCLUSIONS: These preliminary data indicate that end-diastolic images can significantly reduce artifactual defects in patients with LBBB. The resolution of an LBBB pattern on end-diastolic data would significantly improve the diagnostic role of myocardial perfusion studies in these patients.

Exercise-induced ventricular tachycardia in children.

Two children with exercise-induced tachycardia, one with idiopathic long-QT syndrome, are presented. The patients were evaluated by exercise testing and electrophysiologic study. From the onset of treatment with the beta-blocking agent, pindolol, the patients have been symptom-free. These findings emphasize that children with syncope must be evaluated by ECG, exercise testing, 24-h Holter-monitoring, and finally, electrophysiological study.

A common spinal muscular atrophy deletion mutation is present on a single founder haplotype in the US Hutterites.

Spinal muscular atrophy (SMA) is an autosomal recessive (AR) neuromuscular disease that is one of the most common lethal genetic disorders in children, with carrier frequencies as high as ∼1 in 35 in US Whites. As part of our genetic studies in the Hutterites from South Dakota, we identified a large 22 Mb run of homozygosity, spanning the SMA locus in an affected child, of which 10 Mb was also homozygous in three affected Hutterites from Montana, supporting a single founder origin for the mutation. We developed a haplotype-based method for identifying carriers of the SMN1 deletion that leveraged existing genome-wide SNP genotype data for ∼1400 Hutterites. In combination with two direct PCR-based assays, we identified 176 carriers of the SMN1 deletion, one asymptomatic homozygous adult and three carriers of a de novo deletion. This corresponds to a carrier frequency of one in eight (12.5%) in the South Dakota Hutterites, representing the highest carrier frequency reported to date for SMA and for an AR disease in the Hutterite population. Lastly, we show that 26 SNPs can be used to predict SMA carrier status in the Hutterites, with 99.86% specificity and 99.71% sensitivity.