First-degree Family Members Research Articles

Risk of Gastric Cancer is Highly Dependent on Type of First-Degree Family Member Affected by Cancer: Lessons from a High-Risk Population in Iran.

Family history of gastric cancer (GC) in first-degree relatives may increase the risk of GC. This study aimed to assess how family history of GC in first-degree relatives really affects the risk of GC in an extremely high-risk population. A large population-based case-control study was carried out on 1222 incident GC cases and 1235 controls in Ardabil Province-a high-risk area in North-West Iran-to assess the associations of GC family history in first-degree relatives with the risk of GC (2003-2017). GC family history did not significantly associate with the risk of GC overall (ORadj=1.09, 95% CI: 0.80-1.47, P=0.589). It found no significant association of GC family history in a parent, and in a father, mother, and sister separately, with the risk of GC. However, GC risk was significantly associated with a history of GC in a sibling (ORadj=1.61, 95% CI: 1.11-2.35, P=0.013), especially brother (ORadj=2.24, 95% CI: 1.41-3.64, P=0.0008). The risk was greatly increased in subjects with two or more affected brothers (ORadj =5.56, 95% CI: 2.33-14.20, P=0.0002). We did not find a familial tendency to cardia GC and non-cardia GC as well as histopathologic features. Determining the type of first-degree relationships with GC may, therefore, be more important than assessing family history alone for predicting the risk of GC in this high-risk area.

44560 Identifying first-degree family members in patients with FFA and/or LPP in a specialty alopecia clinic

44560 Identifying first-degree family members in patients with FFA and/or LPP in a specialty alopecia clinic

The Assessments of Electrocardiographic Parameters in the Patients with Drug-Resistant Temporal Lobe Epilepsy; A Case-Control Study

Introduction: Sudden unexpected death in epilepsy (SUDEP) is the substantial cause of death in patients with epilepsy (PWE). Electroconductive disorders leading to life-threatening arrhythmia are mostly hypothesized to play a crucial role; however, there is paucity of knowledge in variable among the patients with drug-resistant temporal lobe epilepsy (TLE) compared to the healthy controls. Methods: The current case-control study has been conducted on 50 drug-resistant TLE patients as the cases and 50 age- and gender-matched healthy subjects selected from their first-degree family members. ECGs were taken when admitted at the hospital (base line), immediately after a seizure incidence and within an hour after the end of the seizure from the cases compared with a random ECG of the controls considering parameters including PR-, RR-, and corrected QT interval (QTc), P wave duration and heart rate (HR) variability. Results: Shorter corrected QTc interval was notified among the drug-resistant TLE patients compared to the controls (P-value=0.017) in the base line taken ECGs, while the assessments immediately after the seizure revealed significant differences in terms of RR-interval (P-value=0.005) and heart rate (P-value=0.005). Post-ictal ECGs did not differ between the groups (P-value>0.05). Conclusion: According to the findings of this study, shortened QTc interval at base line ECGs, shortened RR interval and increased HR during the seizure were the ECG elements affected in drug-resistant TLE patients; however, to generalize the outcomes, further studies are required.

Identifying first-degree family members in patients with frontal fibrosing alopecia and lichen planopilaris in a specialty alopecia clinic.

Identifying first-degree family members in patients with frontal fibrosing alopecia and lichen planopilaris in a specialty alopecia clinic.

The familial risk and heritability of multiple sclerosis and its onset phenotypes: A case–control study

Background: The two main phenotypes of multiple sclerosis (MS), primary progressive (PPMS) and relapsing Onset (ROMS), show clinical and demographic differences suggesting possible differential risk mechanisms. Understanding the heritable features of these phenotypes could provide aetiological insight. Objectives: To evaluate the magnitude of familial components in PPMS and ROMS and to estimate the heritability of disease phenotypes. Methods: We used data from 25,186 MS patients of Nordic ancestry from the Swedish MS Registry between 1987 and 2019 with known disease phenotype (1593 PPMS and 16,718 ROMS) and 251,881 matched population-based controls and 3,364,646 relatives of cases and controls. Heritability was calculated using threshold–liability models. For familial odds ratios (ORs), logistic regression with robust sandwich estimator was utilized. Results: The OR of MS diagnosis in those with a first-degree family member with ROMS was 7.00 and 8.06 in those with PPMS. The corresponding ORs for having a second-degree family member with ROMS was 2.16 and 2.18 in PPMS. The additive genetic effect in ROMS was 0.54 and 0.22 in PPMS. Conclusion: Risk of MS increases by several folds in those with a relative with MS. The likelihood of developing either disease phenotype appears independent of genetic predisposition.

Postmortem Genetic Testing in Sudden Unexpected Death in Epilepsy.

A 24-year-old man with non-lesional bi-temporal lobe epilepsy since age 16 years was found dead in bed around midday. He was last seen the previous night when he was witnessed to have a tonic-clonic seizure. Before his death, he was experiencing weekly focal impaired awareness seizures and up to two focal-to-bilateral tonic-clonic seizures each year. He had trialled several antiseizure medications and was on levetiracetam 1500 mg/day, lamotrigine 400 mg/day, and clobazam 10 mg/day at the time of death. Other than epilepsy, his medical history was unremarkable. Of note, he had an older brother with a history of febrile seizures and a paternal first cousin with epilepsy. No cause of death was identified following a comprehensive postmortem investigation. The coroner classified the death as 'sudden unexpected death in epilepsy' (SUDEP), and it would qualify as 'definite SUDEP' using the current definitions.1 This left the family with many questions unanswered; in particular, they wish to know what caused the death and whether it could happen to other family members. Could postmortem genetic testing identify a cause of death, provide closure to the family, and facilitate cascade genetic testing of first-degree family members who may be at risk of sudden death? While grieving family members struggle with uncertainty about the cause of death, we as clinicians also face similar uncertainties about genetic contributions to SUDEP, especially when the literature is sparse, and the utility of genetic testing is still being worked out. We aim to shed some light on this topic, highlighting areas where data is emerging but also areas where uncertainty remains, keeping our case in mind as we examine this clinically important area.

Genetic evaluation of 50 Turkish patients with neurofibromatosis type 1: 2 years experience of a single center.

Neurofibromatosis type 1 is an autosomal dominant neurocutaneous disorder. Clinical diagnosis is difficult in early childhood, and it is possible to miss a critical interval for tumour screening. In this study, we aimed to characterize the mutational spectrum of Turkish patients and discuss the benefits of molecular testing. Fifty individuals from 35 unrelated families were included. Main referral reasons for genetic testing were as follows: to confirm a clinical diagnosis, to use in differential diagnosis and to evaluate first-degree family member of a known patient. Two-step process consisting of initial next generation sequencing of the NF1 gene and consequent multiplex ligation-dependent probe amplification were performed. We identified a total of 30 variants in 28 individuals. Variant detection rate was 56% in the entire study group and 71.4% within the index patients. Four novel variants were found. Truncating variants constituted 60% of the entire mutation spectrum. A deletion or duplication was not detected. The most common feature was cafe au lait macules in 70% of the patients, followed by focal areas of signal intensity on brain imaging (26%), cutaneous neurofibromas (24%) and axillary freckling (24%). Early sequencing in all suspected patients followed by deletion/duplication analysis in patients meeting clinical criteria and a case-to-case based consideration for RNA studies seems to be the effective algorithm for NF-1 diagnosis.

Characterization of 554 Mexican Patients With Nonsyndromic Cleft Lip and Palate: Descriptive Study.

Orofacial clefts are one of the most common birth defects and the most common craniofacial malformation worldwide. The most common orofacial clefts (OFCs) are congenital cleft lip with or without cleft palate (CL ± P) and isolated cleft palate (CP). The incidence of OFCs varies depending on region and ethnicity; however, it affects approximately 1 in 600 newborns worldwide. In most cases, CL ± P and CP are multifactorial congenital malformations, where both exogenous and genetic factors play an important role. The objective of this study was to describe the frequency of potential risk factors associated with the development of CL ± P and CP in Mexican population. Patients were referred for multisystemic treatment, from private and public institutions in different regions of the country (center, north, and south). Sociodemographic information, prenatal and parental history were obtained through direct interviews with the patients or the patients' mothers in the case of underaged patients. Referred patients were invited to participate in the study. No interventions were applied for this study. The relationship between these factors and the prevalence of CL ± P and CP was studied. A total of 554 patients were included, the majority with CLP (30% to 7%), statistically significant differences were found for folic acid ( P = 0.02) consumption. Familial aggregation did not reach statistical significance for first-degree family members ( P = 0.34) but was significant for second-degree family members ( P = 0.007). More risk factors associated with CL ± P and CP may still be unknown, prompting more epidemiological research and research in other little-studied areas, such as; specific genetic factors in Mexican population.

Embolization of a Transplanted Kidney in MELAS Requires Special Considerations

With interest we read the article by Kim et al. on an 18 year-old female with mitochondrial encephalopathy, lactic acidosis, and stroke-like episode (MELAS) syndrome, who underwent en block kidney transplantation (EBKT) because of renal failure due to glomerulosclerosis [1]. Two months after transplantation the patient experienced urinary tract infection due to hydronephrosis of the left transplanted kidney [1]. Despite all measures to preserve the left kidney, hydronephrosis was classified as intractable and it was decided to sacrifice the culprit kidney and to embolise it which was technically difficult because of kinking, multiple renal arteries, but was lastly successful [1]. The study is excellent, but has limitations that are cause of concerns and should be discussed. The main limitation of the study is that it was not mentioned how MELAS was diagnosed and that the causative mutation responsible for MELAS was not reported. Knowing the underlying genetic defect is crucial as it may allow assessing the prognosis and may facilitate genetic counselling. Since 80% of the MELAS patients carry the mtDNA variant m.3243A>G in MT-TL1, we should know if MELAS in the index patient was due to this common cause of MELAS and whether other first-degree family members also carried this variant. Knowing whether an mtDNA or nDNA located gene was mutated is critical, as the phenotypic expression of mtDNA located genes is strongly dependent on heteroplasmy rates and mtDNA copy number. Knowing the nature of the underlying mutation is also critical for choosing the optimal immunosuppressive treatment after transplantation, as immunosuppressants can be mitochondrion-toxic. Another limitation is that it is unclear whether the index patient had inherited the pathogenic variant from her parents or whether it had occurred de novo. Knowing whether kidney failure due to glomerulosclerosis was inherited is critical as the index patient would transmit the causative mutation if it was inherited but may not inherit the defect to the next generation if the mutation had occurred de novo. We should know why the left kidney was embolized and not explanted. Because recurrent infections were made responsible for hydronephrosis, it cannot be ruled out that the left kidney hosted microbial agents, which could be a permanent source of bacteriemia or viremia. Therefore, we should know the long-term outcome after embolization. Did the index patient still experience recurrent urinary tract infections or was renal function completely restored after embolization? There is not mention, whether the complicated anatomy, multiple angulations, accessory renal arteries were present already immediately after transplantation or whether they developed during the time between transplantation and the development of hydronephrosis. Were the multiple renal arteries already described in the operation report? Knowing the pathophysiology of multiple renal arteries and kinking is crucial for future cases. Hydronephrosis was attributed to ureter obstruction but there is no discussion of its pathophysiology. We should know whether ureter obstruction was due to host-versus graft reaction, due to ureteritis, due to spasms, or due to ureter stones. Overall, the interesting study has limitations that call the results and their interpretation into question. Addressing these issues would strengthen the conclusions and could improve the status of the study. Complications after kidney transplantation in MELAS patients require special attention and management.

Special Report: Autism Spectrum Disorder and Inflexible Thinking—Affecting Patients Across the Lifespan

Special Report: Autism Spectrum Disorder and Inflexible Thinking—Affecting Patients Across the Lifespan

Profile and Post-Kidney Retrieval Outcomes in Asymptomatic Kidney Donors With Genetic Mutations in Complement Factors–Related Genes

BackgroundAtypical hemolytic uremic syndrome (aHUS) is a rare disorder triggered by various stressors. Most of the time, stressors may not be identified in patients with aHUS. The disease may remain quiescent without manifestation throughout life. BackgroundTo assess the outcome of an asymptomatic carrier of genetic mutations of patients with aHUS who had undergone donor kidney retrieval surgery. MethodsWe retrospectively included the patients diagnosed with a genetic abnormality in complement factor H (CHF) or CHF-related (CFHR) genes without manifestation of the aHUS and who had undergone donor kidney retrieval surgery. The data were analyzed with descriptive statistics. ResultsAmong patients who were the kidney recipients from the prospective donors, 6 donors were screened for genetic mutations in CFH and CFHR genes. Four donors showed positive mutation for CFH and CFHR. The mean age was 54.5 years (range, 50-64 years). After over a year since donor kidney retrieval surgery, all prospective mother donors are alive without aHUS activation and with a normal kidney function on a single kidney. ConclusionAsymptomatic carriers of genetic mutations in CFH and CFHR can be the prospective donors for their first-degree family member who have active aHUS. A genetic mutation in an asymptomatic donor should not be a contraindication for refuting the prospective donor.

Cohort profile: Celiac disease genomic, environmental, microbiome and metabolome study; a prospective longitudinal birth cohort study of children at-risk for celiac disease.

The Celiac Disease Genomic, Environmental, Microbiome and Metabolomic (CDGEMM) study is an international prospective birth cohort in children at-risk of developing celiac disease (CD). The CDGEMM study has been designed to take a multi-omic approach to predicting CD onset in at-risk individuals. Participants are required to have a first-degree family member with biopsy diagnosed CD and must be enrolled prior to the introduction of solid food. Participation involves providing blood and stool samples longitudinally over a period of five years as well as answering questionnaires related to the participant, their family, and environment. Recruitment and data collection have been ongoing since 2014. As of 2022 we have a total of 554 participants and the average age of the cohort is 56.4 months. A total of 54 participants have developed positive antibodies for CD and 31 have confirmed CD. Approximately 80% of the 54 participants with CD have developed it by 3 years of age. To date we have identified several microbial strains, pathways, and metabolites occurring in increased abundance and detected before CD onset, which have previously been linked to autoimmune and inflammatory conditions while others occurred in decreased abundance before CD onset and are known to have anti-inflammatory effects. Our ongoing analysis includes expanding our metagenomic and metabolomic analyses, evaluating environmental risk factors linked to CD onset, and mechanistic studies investigating how alterations in the microbiome and metabolites may protect against or contribute to CD development.

The Role of Genetic Testing in Patients with Heritable Thoracic Aortic Diseases

Heritable thoracic aortic disease (HTAD) is a term used to define a large group of disorders characterized by the occurrence of aortic events, mainly represented by aneurysm or dissection. These events generally involve the ascending aorta, although the involvement of other districts of the aorta or peripheral vessels may occur. HTAD can be classified as non-syndromic if the disorder is limited to the aorta, and syndromic when associated with extra-aortic features. About 20-25% of patients with non-syndromic HTAD exhibit a family history of aortic disease. Thus, a careful clinical evaluation of the proband and the first-degree family members is required to differentiate familial and sporadic cases. Genetic testing is essential since it allows confirmation of the etiological diagnosis of HTAD (particularly in patients with a significant family history) and may guide family screening. In addition, genetic diagnosis significantly impacts patients' management since the different conditions significantly differ with respect to natural history and treatment strategies. The prognosis in all HTADs is determined by the progressive dilation of the aorta, potentially leading to acute aortic events, such as dissection or rupture. Moreover, the prognosis varies according to the underlying genetic mutations. This review aims to describe the clinical characteristics and natural history of the most common HTADs, with particular emphasis on the role of genetic testing in risk stratification and management.

Association among Cases of Women with first degree Family History of Diabetes Mellitus, Previous Macrosomia and Preterm Births, and Pregnancy Weight Gain at Mama Lucy Kibaki Hospital, Nairobi City

Background: Weight gain during pregnancy is of great concern for most women and obstetricians because of its possible consequences. This concern exists because gestational weight gain that exceeds what is recommended by the Institute of Medicine is associated with many maternal and fetal complications. While excessive gestational weight gain (GWG) is associated with modifiable risk factors for Gestational Diabetes Mellitus (GDM) notably, obesity and overweight conditions, there is a paucity of information on the association of cases of excessive GWG with non-modifiable risk factors (NMRF) for GDM namely history of diabetes mellitus in the first-degree family members as well as previous macrosomia and preterm deliveries. Method: The study prospectively monitored GWG in 337 women with a history of diabetes mellitus in first-degree family members as well as previous macrosomia and preterm deliveries. Data collected was analysed through bivariate regression to determine the odds of excessive GWG in the presence and absence of each of the three non-modifiable risk factors. Results: The non-modifiable risk factors of women of all BMIs were not found to be significantly associated with excessive GWG. For instance, a family history of DM in obese women was not associated with excessive GWG (P = 0.254; AOR = 0.715; 95%CI: 0.401-1.272). History of macrosomia in obese women was also not statistically significant (P = 0.973; AOR = 1.015; 95% CI: 0.429-2.402). Similarly, history of preterm births in obese women was not significantly associated with excessive GWG (P = 0.778; AOR = 0.902; 95%CI: 0.441-1.847). Conclusion: History of macrosomia and preterm births as well as family history of Diabetes mellitus cannot serve as predictors for excessive GWG because there is no association among them and excessive GWG by women of all BMIs

Patients' Expectations and Preferences for the Organizational Conditions of the Colorectal Cancer Screening Programme in Poland: A Qualitative Analysis.

(1) Background: Colorectal cancer (CRC) is a serious health problem in Poland as well as many European Union countries. The study aimed to describe factors that, from the patient's perspective, could increase the attendance rate and regularity of participation in the colorectal cancer screening programme (SP); (2) Methods: The qualitative approach was applied. The study involved six focus interviews conducted with 24 respondents (12 women and 12 men) aged 40-49, who had at least one first-degree family member diagnosed with CRC and persons aged 50-65, living in five selected voivodships (provinces) of Poland. The collected data were thematically coded. Further, a comparative analysis was conducted, and aggregated statements were formulated; (3) Results: The inclusion of primary care clinics within the CRC SP organization was reported as a key factor in improving the attendance rate and regularity of patient participation in the programme. Particularly important factors included an invitation in the form of a personal letter or a phone call made by staff from primary care clinics; (4) Conclusions: Patients were confirmed to have clear expectations and preferences for the organizational conditions of the CRC SP. Preferences nature allows them to be treated as one of the potential criteria for selecting critical parameters of CRC SPs.

Association of dietary intake with body mass index and glycemic profile among newly diagnosed patients with type 2 diabetes mellitus.

Dietary intake plays an important role in determining body mass index (BMI) and glycemic profile in patients with type 2 diabetes mellitus (T2DM). Our aim was to describe habitual dietary intake and its associations with BMI and glycemic profile in a cohort of patients with newly diagnosed T2DM in Sri Lanka. A cross-sectional study was carried out among 158 patients with newly diagnosed T2DM in Galle, Sri Lanka. Data on demographic, lifestyle, and family history of diabetes mellitus, and clinical measures were collected. The dietary information was collected using a 24-h dietary recall. Among the total number of study subjects, only 12.0%, 5.7% and 1.3% met the recommended daily consumption value of protein, fat, and fiber, respectively, whereas 99.4% of subjects had taken carbohydrates that exceeded the recommended consumption. There was a positive association between carbohydrate intake and BMI (0.004, [0.002], p=.048) and carbohydrate intake and glycated hemoglobin (HbA1C ) (0.001, [0.000], p=.049). Fat intake showed positive associations with BMI (0.029, [0.011], p=.006) and HbA1C (0.005, [0.002], p=.050). Protein intake showed a positive association with HbA1C (0.006, [0.003], p=.023). The aforementioned associations were observed after adjusting for demographic, lifestyle, and history of diabetes among the first-degree family members. The carbohydrate intake was positively associated with BMI (0.010, [0.003], p=.003) and HbA1C (0.001, [0.000], p=.050) with further adjustment in nutrient intake (except when used as an independent variable). Furthermore, the fat intake was associated with BMI (0.031, [0.011], p=.004) and HbA1C (0.005 [0.002], p=.050) with additional adjustments. The diet of the majority of newly diagnosed T2DM patients in this cohort consisted of a higher carbohydrate intake than the recommended level. However, they did not meet the recommended daily intake of protein, fat, and fiber. Both carbohydrate and fat intake were significantly and positively associated with BMI and HbA1C in patients with newly diagnosed T2DM.

Optimizing Screening for Early Disease Detection in Familial Pulmonary Fibrosis (FLORIS): A Prospective Cohort Study Design.

Background: Familial pulmonary fibrosis (FPF) can be defined as pulmonary fibrosis in two or more first-degree family members. The first-degree family members of FPF patients are at high risk of developing FPF and are eligible for screening. Reproducible studies investigating risk factors for disease are much needed. Methods: Description of the screening study protocol for a single-center, prospective cohort study; the study will include 200 asymptomatic, first-degree family members of patients with FPF who will undergo three study visits in two years. The primary objective is determining the diagnostic value of parameters for detection of early FPF; the secondary objectives are determining the optimal timing of the screening interval and gaining insight into the natural history of early FPF. The presence of interstitial lung disease (ILD) changes on high-resolution computed tomography of the chest is indicative of preclinical ILD; the changes are determined at baseline. The comparison between the group with and without ILD changes is made for clinical parameters (pulmonary function, presence of digital clubbing, presence of Velcro-like crackles, blood count, liver- and kidney-function testing, patient-reported cough and dyspnea score) and exploratory parameters. Discussion: This study will be the first large-size, prospective, longitudinal cohort study for yearly screening of asymptomatic family members of FPF patients investigating the diagnostic value of parameters, including lung function, to detect early FPF. More effective screening strategies could advance early disease detection.

Increased Number of Functional Tics Seen in Danish Adolescents during the COVID-19 Pandemic.

Global increase in functional tics in adolescents has been observed. Differentiating functional from classic tics is important since pathophysiology and treatment differ. We investigated possible triggers for development of functional tics and discuss the possible role of the coronavirus disease 2019 (COVID-19) pandemic and social media exposure in cases of functional tics seen during this period. Moreover, the treatment, and its efficacy is discussed. Medical records of 28 Danish adolescents diagnosed with functional tics at the National Tourette Clinic, Department of Pediatrics, Herlev University Hospital, Denmark, from May 2020 to June 2021 have been retrospectively reviewed. Descriptive statistical analyses were used to analyze the data. A total of 28 patients diagnosed with functional tics were included, 96.4% girls and 3.6% boys, mean age 14.4 years. Tic phenomenology differed from classic tics with more complex tics and no rostrocaudal progression. Note that 69.2% reported harmful tics. Also, 78.6% had trauma/precipitating event and 40% denounced lockdown related to the COVID-19 pandemic as trigger, both prior to onset of functional tics. Note that 60.7% reported psychiatric symptoms/diagnoses, 42.9% had a first-degree family member with psychiatric symptoms/diagnoses, and 96.4% were exposed to tics on social media prior to onset. Treatment consisted of psychoeducation, elements from cognitive behavioral therapy, and focus on psychiatric symptoms. All patients responded to the treatment. The vulnerability of the adolescents is characteristic. Treatment strategy has shown immediate positive effect. Consequences of the COVID-19 pandemic in combination with exposure to tics on social media could be part of the cause for the increase in number of functional tics.

Basic Research Protocol: Exome Sequencing in Adults With Loin Pain Hematuria Syndrome: A Pilot Study.

Loin pain hematuria syndrome (LPHS) is a poorly understood clinical syndrome characterized by hematuria and either unilateral or bilateral severe kidney pain in the absence of identifiable urological disease. Loin pain hematuria syndrome imposes a significant health and economic impact with a loss of productivity and quality of life in a young population. Owing to an incomplete understanding of its pathophysiology, treatment has been limited to nonspecific pain management. Nearly 60 years after its initial description, we are no further ahead in understanding the molecular pathways involved in LPHS. To outline the study design for exome sequencing in adults with LPHS and their families. In this single-center case series, 24 patients with LPHS and 2 additional first-degree family members per participant will be recruited. DNA extracted from venous blood samples will undergo exome sequencing on the Illumina NovaSeq 6000 System at 100× depth and will be assessed for pathogenic variants in genes associated with hematuria (number of genes in: glomerular endothelium [n = 10] and basement membrane [n = 8]), and pain pathways (number of genes in: pain transduction [n = 17], conduction [n = 8], synaptic transmission [n = 37], and modulation [n = 27]). We will further examine identified potentially pathogenic variants that co-segregate with LPHS features among affected families. This pilot study may identify new directions for an investigation into the molecular mechanisms underlying LPHS.

Abstract 13143: Genetic Testing Referral Patterns Among Women With Peripartum Cardiomyopathy

Introduction: The genetic architecture of peripartum cardiomyopathy (PPCM) and dilated cardiomyopathy (DCM) overlap, and 15% of patients with PPCM have a disease-causing variant in a DCM-associated gene. Despite the impact of genetics on cascade screening and risk stratification, there are no recommendations for genetic testing in PPCM. We aimed to quantify the percentage of individuals with PPCM referred for genetic testing and to identify factors that may impact the likelihood of referral for genetic testing. Methods : We conducted a retrospective cohort study of 205 patients diagnosed with PPCM from 1986-2018 within the University of Pennsylvania Health System who had outpatient follow-up. We determined the referral rate for genetic testing and examined differences in referral based on race, timing of PPCM diagnosis, hypertensive disorders of pregnancy (HDP), NYHA class at diagnosis, LVEF at diagnosis, family history, recurrent PPCM, and referral to a heart failure specialist. We compared continuous variables using the Student t test and categorical variables using Pearson’s chi-square test. Results : Of 205 patients with PPCM, 23 (11%) were referred for genetic testing. Women referred for genetic testing were more likely to have HDP (61% vs. 37%, p=0.03), LVEF <30% at diagnosis (65% vs. 42%, p=0.04), recurrent PPCM (17% vs. 5%, p=0.04), a first-degree family member with heart failure or cardiomyopathy (70% vs. 17%, p<0.001), and any documented family history at the first cardiology visit (78% vs. 54%, p=0.03). Of those referred, 17 (74%) underwent genetic counseling, and 12 (52%) completed genetic testing. Two patients (17%) had a pathogenic or likely pathogenic variant in TTN and were recommended for cascade screening, and 9 (75%) had variants of unknown significance which were predominately missense variants. Conclusions : A minority of women with PPCM are referred for genetic testing. Referral is largely driven by family history, which may lead to under-diagnosis of pathogenic mutations. Increasing referral rates may improve the detection of pathogenic mutations which may impact the care provided to affected women and their families.