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Introduction: Townes-Brocks syndrome (TBS), a rare autosomal dominant genetic condition associated with SALL1 (Spalt like Transcription Factor 1), is reported to be present in 1:238,000 individuals in the general population. TBS is characterized by the triad of anorectal malformations, dysplastic ears, with or without hearing impairment, and hand or thumb anomalies. Although kidney involvement is less common in TBS, the disease can progress to kidney failure. Here, we sought to characterize the incidence of SALL1 variants in individuals undergoing broad-based genetic testing with a kidney gene panel and to quantify the presence of (extra)renal features. Methods: A retrospective analysis of the genetic data from a 385-gene panel identified cases with a pathogenic (P) or likely pathogenic (LP) variant in SALL1. Data including age, features, and disease progression were collected. Results: Of 35,044 samples, P or LP variants in SALL1 were identified in 22, yielding a prevalence of 1:1592 among patients tested for monogenic kidney disease, and 1:342 among cases identified with a monogenic kidney disease. Among this cohort, the median patient age was 23 years (range: 3 months-62 years) with chronic kidney disease (CKD) reported in 91% (20/22) of cases. Reported kidney features included renal agenesis/hypoplasia (7/22; 32%), focal segmental glomerulosclerosis (4/22; 18%), and kidney cysts (3/22; 14%). Confirmed extrarenal features included hearing loss and/or ear features (7/22; 32%), anorectal malformations (6/22; 27%) and hand or thumb abnormalities (4/22; 18%). Three patients (3/22; 14%) had both a priori TBS diagnoses and the traditional "triad." Conclusion: Traditionally, a molecular diagnosis was ascertained primarily in individuals presenting with cardinal features of TBS; therefore, individuals with mild or atypical presentations were often overlooked clinically. Our findings reveal that SALL1 P/LP variants could be a consequential contributor to monogenic kidney disease.
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As genetic testing is increasingly integrated into nephrology practice there is a growing need for partnership with genetic experts. Genetic counselors are ideally suited to fill this role. The value of genetic counseling is born out of the clinical value of genetic test results against the backdrop of the complexity of genetic testing. Genetic counselors who specialize in nephrology are trained to understand and explain the potential effects of genes on kidney disease, which can enable patients to make informed decisions about proceeding with genetic testing, navigating variants of uncertain significance, educating on extrarenal features of hereditary kidney disease, facilitating cascade testing, providing post-test education about testing results, and assisting with family planning. Genetic counselors can partner with the nephrologist and provide the knowledge needed to maximize the use of genetic testing for patients for nephrology consultation. Genetic counseling is more than an element or extension of genetic testing; it is a dynamic, shared conversation between the patient and the genetic counselor where concerns, sentiments, information, and education are exchanged, and value-based decision making is facilitated.
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We present two siblings with persistent proteinuria and normal kidney function, each carrying the same compound heterozygous variants in the CUBN gene. The CUBN-related phenotype appears to be dependent upon both variant type and the domain site within the gene. Knowledge of CUBN status may allow for avoidance of invasive testing.
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BACKGROUND: Sickle cell disease (SCD) and autosomal dominant polycystic kidney disease (ADPKD) are relatively common genetic conditions with considerable overlap in clinical presentation. In addition to similarities between the signs and symptoms in sickle cell nephropathy and ADPKD, more than half of SCD patients have kidney cysts. The co-occurrence of these two diseases has not been previously reported in the literature. CASE DIAGNOSIS/TREATMENT: A 16-year-old Black male with SCD had bilateral kidney enlargement and multiple simple cysts on ultrasound. Although kidney cysts are significantly more common in individuals affected with SCD, genetic testing with a broad kidney gene panel was performed to explore the possible presence of another underlying genetic cause of his cysts, in addition to SCD. A dual diagnosis of SCD and ADPKD was made following the identification of two copies of the common pathogenic sickle cell HBB variant (c.20A > T, p.Glu7Val) and a pathogenic missense variant in PKD1 (c.8311G > A, p.Glu2771Lys). CONCLUSIONS: SCD and ADPKD differ in pathophysiological mechanisms and treatment regimens. As such, it will be paramount for this teenager to be closely monitored for signs of diminished kidney function and to be co-managed as he transitions to adult care to ensure proper treatment and management. Early identification of individuals with both SCD and a co-occurring condition is crucial to ensuring proper clinical management. Furthermore, identifying and reporting additional patients with SCD and ADPKD dual diagnoses will help us to understand the co-occurring disease course and optimal treatments.
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Anemia de Células Falciformes , Quistes , Neoplasias Renales , Riñón Poliquístico Autosómico Dominante , Adulto , Humanos , Masculino , Adolescente , Riñón Poliquístico Autosómico Dominante/complicaciones , Riñón Poliquístico Autosómico Dominante/diagnóstico , Riñón Poliquístico Autosómico Dominante/genética , Diagnóstico Dual (Psiquiatría) , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/diagnóstico , Anemia de Células Falciformes/genética , Canales Catiónicos TRPP/genéticaRESUMEN
South Dakota's Newborn Screening (NBS) program has been in existence for nearly 50 years. What began as a screen for a single condition has now expanded to more than 50 conditions. From 2005-2019 alone, 315 infants were confirmed as positive for a condition detected by the newborn screen in South Dakota. This article summarizes the process of newborn screening in South Dakota, the role of the primary care physician when caring for an infant with a positive screen, the groups of conditions which are included on the South Dakota NBS panel, how NBS changed over time, and the process for adding conditions to the South Dakota NBS panel.
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Mortalidad Infantil , Tamizaje Neonatal , Lactante , Recién Nacido , Humanos , South DakotaRESUMEN
INTRODUCTION: A major goal of the current personalized medicine era is to utilize pharmacogenetics (PGx) in order to influence how medications and therapies are prescribed by providers. However, disparities for prescribing medications between adults and children exist. Research has shown that children are not just small adults and there are different challenges for pediatric providers in regards to ordering and interpreting PGx tests. The goal of this study was to obtain an initial understanding of current pharmacogenetic testing by pediatric providers, as well as determine perceived barriers. METHODS: We distributed an online survey to pediatric providers at six different institutions across the U.S. RESULTS: Of the 252 respondents who completed the survey, 24 percent reported previously ordering PGx tests, however, over 90 percent of respondents reported they would feel more comfortable ordering and interpreting results with the assistance of a pharmacist, geneticist, genetic counselor or PGx expert. Additionally, participants identified specific barriers towards the utilization of PGx testing, as well as suggested solutions to overcome these barriers, including increasing provider education regarding testing, collaboration through a multidisciplinary team approach and established PGx programs. CONCLUSION: As the pharmacogenetic field continues to demonstrate clinical utility in the pediatric population, it will be important to continuously identify and address barriers that exist for providers to allow for more successful implementation of PGx in the pediatric setting, as well as enhance patient care.
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Farmacogenética , Médicos , Adulto , Niño , Humanos , Farmacéuticos , Pruebas de Farmacogenómica , Medicina de PrecisiónRESUMEN
In recent years, it has become apparent that patients expect genetic counselors to be able to address questions about insurance coverage for genetic testing and perform 'genesurance' tasks in and out of genetic counseling sessions. Anecdotally, many genetic counseling graduate programs have begun to incorporate genesurance training in some capacity. However, the amount, modality, and potential barriers to this training had not been previously studied; therefore, this study aimed to elucidate current graduate program practice regarding genesurance. Program Directors of Accreditation Council for Genetic Counseling (ACGC) accredited programs who had students enrolled as of July 2019 (n = 50) were recruited through the Association of Genetic Counseling Program Directors (AGCPD) listserv and invited to complete an anonymous electronic survey via Qualtrics. Program Directors (PDs) from 25 ACGC accredited programs located in the United States completed the survey and were included in the analysis, responses from two ACGC Canadian programs were excluded due to small sample size and differences in healthcare systems. Responses were analyzed using descriptive statistics and open-ended responses were coded utilizing latent qualitative content analysis. The majority of respondents from the United States, 96.0% (24/25), report incorporating genesurance training into their curriculum utilizing a variety of training modalities including classroom, clinical, and online experiences. Most (81.0%) felt their trainees were adequately or very prepared to discuss genesurance issues. Despite varied methods of teaching modalities, PDs identified barriers to providing this training, including time constraints within the curriculum, lack of interest in the subject, as well as acknowledging the constantly changing landscape of billing and insurance. Despite these barriers, a baseline understanding of the impact of insurance on offering genetic testing and insight into how insurance impacts clinical practice may be beneficial to genetic counseling trainees, as it reflects the current genetic counselor's workflow and practice patterns.
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Consejeros , Asesoramiento Genético , Acreditación , Canadá , Consejo , Curriculum , Educación de Postgrado en Medicina , Asesoramiento Genético/psicología , Humanos , Encuestas y Cuestionarios , Estados UnidosRESUMEN
The number of certified genetic counselors (CGCs) in the genetic counseling workforce has increased over the past few decades as the number of training programs increases and CGCs expand into new patient-facing and non-patient-facing roles. Few studies have explored the distribution of CGCs across the United States. We sought to identify the U.S. geographical regions with the highest number of CGCs and those regions where the physical presence of CGCs is sparser. Deidentified city, state, and ZIP code information for each CGC in the United States were obtained from the American Board of Genetic Counseling (ABGC) database. A countrywide analysis of the distribution of CGCs was completed using geographic information system (GIS) mapping software. The data were organized into U.S. metropolitan or micropolitan statistical areas, if applicable, and analyzed by CGC per capita. We included a total of 4,554 data points (92.2%) in the analysis. Results showed there is one CGC for every 71,842 people nationwide. Of 3,141 total counties (or county equivalents) in the United States, 535 counties had at least one CGC (17.0%). The majority (98.7%) of CGCs live or work within metropolitan statistical areas (MSAs), which are defined by this study as geographical areas with greater than 50,000 people. Of the MSAs with a CGC, approximately half have more than one CGC per 100,000 people. These results are consistent with the overall distribution of the U.S. population. We believe that the MSAs with the most CGCs per capita are due to associations with specific institutions, that is, genetic counseling training programs, health system headquarters, or genetic laboratories. Although the present study cannot draw definite conclusions regarding direct patient care services provided by CGCs, it does provide a snapshot of current CGC distribution within the country. Knowing the distribution of CGCs provides a tool to conduct further workforce analyses to determine the number of CGCs needed to serve the U.S. population.
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Consejeros , Certificación , Consejo , Asesoramiento Genético , Humanos , Estados Unidos , Recursos HumanosRESUMEN
Genetic counseling careers continue to evolve, yet there remains a lack of information about hiring trends in the genetic counseling profession. In this study, job advertisements in the United States and Canada were analyzed, using the National Society of Genetic Counselors (NSGC) Job Connections and the American Board of Genetic Counseling (ABGC) eBlasts from 2014 to 2016 to appraise job roles, qualifications, settings, specialties, and type. NSGC had 1875 advertised openings from 2014 to 2016, while ABGC had 373 advertised openings. Jobs containing a "counseling" role increased as a percentage from 2014 to 2016 when advertised by NSGC (χ2 = 25.52, p < 0.000001) but decreased each year from 2014 to 2016 as a percentage when advertised through ABGC (χ2 = 14.29, p = 0.0008). In the ABGC job postings, it was noted that 36% of job postings were advertised for other specialties (not solely cancer, pediatric, or prenatal) in 2014, and increased to 67% in 2016 (χ2 = 10.09, p = 0.02). Examining the job specialties posted by ABGC and NSGC, several new or unique roles were found in the job advertisements such as ophthalmology counselor, variant curator, rare diseases information specialist, and clinical policy analyst. Roles for temporary, contract or fellowship positions are possibly becoming more common, along with small upturns in positions that are off-site or remote. In analyzing the changing workforce, there was a statistically significant decrease identified in jobs advertised by NSGC in the laboratory setting from 28% in 2014 to 17% in 2016 (χ2 = 24.12, p = 0.000024). This information on the evolving career of genetic counseling is valuable for the current workforce and training programs as they adapt with the changing landscape of the profession.
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Publicidad , Asesoramiento Genético , Selección de Personal , Canadá , Consejeros , Humanos , Estudios Retrospectivos , Estados Unidos , Recursos HumanosRESUMEN
Compared to demographic data from other healthcare professions, genetic counselors (GCs) are more likely to be Caucasian females. Many current underrepresented in genetic counseling (URGC) professionals in the field found genetic counseling later in their careers due in part to their lack of awareness. A pilot study consisting of equal numbers of male and female sixth grade science club students was conducted to explore the impact that direct teaching might have on students' awareness of and interest in genetic counseling. The analysis used the non-parametric Wilcoxon signed rank test due to the ordinal, Likert-scale data. Results derived from a pre- and post-survey of lesson participants indicated a statistically significant increase in students' perceptions of having a role model in a science career. Efforts to reach local middle school students to highlight genetic counseling as a potential career choice, especially by role models, may add to the continued work being done to increase the diversity of future genetic counseling applicant pools.
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Genetic counseling is a communication process whereby an individual or family obtains information about a genetic condition, is helped to understand the implications and significance of the condition, and is given resources to help with coping and management. It is a continuous process involving lasting supportive relationships between the family and the genetic professional. Genetic counselors are master's level-trained health-care professionals who work closely with pediatricians and pediatric subspecialists alike. Genetic counselors can be a source of information about genetic conditions, risk assessment for disease, and genetic testing. Although most of a genetic counselor's job is patient care and education, genetic counselors also serve as resources to educate health professionals about genetics.
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Asesoramiento Genético , Pediatría , Niño , Consejeros , Pruebas Genéticas/métodos , Genética Médica/métodos , HumanosRESUMEN
SATB2-associated syndrome (SAS) is an autosomal dominant disorder characterized by significant neurodevelopmental disabilities with limited to absent speech, behavioral issues, and craniofacial anomalies. Previous studies have largely been restricted to case reports and small series without in-depth phenotypic characterization or genotype-phenotype correlations. Seventy two study participants were identified as part of the SAS clinical registry. Individuals with a molecularly confirmed diagnosis of SAS were referred after clinical diagnostic testing. In this series we present the most comprehensive phenotypic and genotypic characterization of SAS to date, including prevalence of each clinical feature, neurodevelopmental milestones, and when available, patient management. We confirm that the most distinctive features are neurodevelopmental delay with invariably severely limited speech, abnormalities of the palate (cleft or high-arched), dental anomalies (crowding, macrodontia, abnormal shape), and behavioral issues with or without bone or brain anomalies. This comprehensive clinical characterization will help clinicians with the diagnosis, counseling and management of SAS and help provide families with anticipatory guidance.
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Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Proteínas de Unión a la Región de Fijación a la Matriz/genética , Fenotipo , Factores de Transcripción/genética , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/genética , Adolescente , Adulto , Niño , Preescolar , Facies , Femenino , Estudios de Asociación Genética/métodos , Humanos , Lactante , Patrón de Herencia , Masculino , Polimorfismo de Nucleótido Simple , Síndrome , Adulto JovenRESUMEN
Genetic counselors (GCs) have reported an increase in discussion of insurance-related, or "genesurance," topics during genetic counseling sessions. Despite increasing frequency, there have been no studies examining patient expectations of GCs in these discussions. This study aimed to explore patient expectations of GCs in these discussions, as well as examine factors that may impact expectations. A 38-item survey was administered prior to patients receiving prenatal or cancer genetic counseling at 11 clinic sites across UTHealth, Baylor College of Medicine, and Sanford Health, with 360 responses analyzed. Key variables were analyzed using descriptive statistics, chi-square analysis, and multivariate logistic regression to assess associations between factors and control for potential confounders. Over 75% of patients expected GCs to discuss genesurance topics during a genetic counseling session. The majority of patients (78%) expected GCs to provide an estimated out-of-pocket cost, know if a test is a covered benefit (77%), and provide referral information for further questions (76%). Two additional expectations, considered to be unrealistic in most clinical settings, included expecting GCs to know the patient's specific insurance plan and coverage information (57%) and provide an exact out-of-pocket cost (41%). Ethnicity was the only significant predictor of response for these two expectations, as African Americans and Hispanics were more likely than Caucasians to have these beliefs. While the patient participants felt that GCs were primarily responsible for initiating these conversations, they also reported a personal sense of responsibility for raising questions. This study demonstrates that patients may expect GCs to address genesurance topics in a genetic counseling session, with specific expectations about the cost and coverage of genetic tests. Further studies will establish the most effective way to communicate this information to patients and examine whether and where within the scope of GC practice, genesurance discussions fall.
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Asesoramiento Genético/psicología , Atención Prenatal/métodos , Adolescente , Adulto , Femenino , Pruebas Genéticas , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/genética , Embarazo , Encuestas y Cuestionarios , Adulto JovenRESUMEN
In-person genetic counseling clinics in rural areas are likely to improve access to genetic counseling in underserved regions, but studies have not previously examined how these clinics function or described the experience of practicing in a rural setting. The present mixed-methods study explored the professional experiences of clinical genetic counselors who practice in rural areas, including the benefits and challenges of practicing in these settings and the counselors' motivations for doing so. The authors surveyed 20 genetic counselors who self-reported working in rural areas and conducted interviews with six individuals whose workplaces were confirmed as rural per RUCA code. Major obstacles to the provision of genetics services in rural areas included travel distance and low referral rates due to lack of awareness or skepticism. Facilitating factors included relying on resources such as professional networks and prioritizing outreach and education. Participants reported high professional satisfaction and were motivated to work in rural areas by personal experiences and qualities of the job such as being a generalist and having greater professional autonomy. These data demonstrate the feasibility of practicing in rural settings and suggest that in-person rural genetic counseling clinics may complement other strategies such as alternative service delivery models in increasing access for rural residents.
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Consejeros/psicología , Asesoramiento Genético/psicología , Servicios de Salud Rural/organización & administración , Población Rural , Adulto , Concienciación , Femenino , Humanos , Masculino , Investigación Cualitativa , Encuestas y CuestionariosRESUMEN
While traditional components of genetic counseling sessions are well recognized, less is known about insurance and financial discussions. This study sought to examine "genesurance counseling" which we defined as: that portion of a genetic counseling session, whether intentional or non-intentional, that is devoted to the topic of costs and insurance/third party coverage (particularly for genetic testing). Our objective was to assess genetic counselors' practices and perspective related to genesurance counseling. A survey link was sent by e-mail to members of the National Society of Genetic Counselors (approximately 3100 NSGC members). A total of 571 genetic counselors participated in the survey of which 550 identified as clinical genetic counselors. Survey data were used to investigate differences between specialties, impact on patient rapport, changes in practice dynamics, and devotion of clinic time. Overwhelmingly, 99% of participants acknowledged conducting genesurance counseling, 87% believed it to be part of their job description, and 85% viewed it as an important aspect of genetic counseling. On average, respondents estimated they devoted 10% of their session, or 6 min, to genesurance counseling. Of the surveyed participants, 95% reported genesurance counseling as having some form of influence in a patient's decision regarding genetic testing, and 74% stated that genesurance counseling concerns change the practice and dynamic of their clinic. "Genesurance counseling" is not a topic which has been studied to date. Our study highlights the changes in genetic counselors' roles and responsibilities regarding insurance and financial counseling.
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Consejeros , Asesoramiento Genético , Cobertura del Seguro , Rol Profesional , Adulto , Femenino , Asesoramiento Genético/economía , Pruebas Genéticas , Humanos , Masculino , Conducta Social , Encuestas y CuestionariosRESUMEN
Uniparental disomy (UPD), where two copies of genetic material are from one parent, and none from the other, is a familiar cause of imprinting. We present a premature infant with organomegaly and congenital hyperinsulinism found to have complete UPD of paternal origin as determined by Mendelian inheritance error analysis.
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Síndrome de Beckwith-Wiedemann/diagnóstico , Síndrome de Beckwith-Wiedemann/genética , Impresión Genómica , Disomía Uniparental/diagnóstico , Padre , Humanos , Lactante , Masculino , Disomía Uniparental/genéticaRESUMEN
Developmental and epileptic encephalopathy (DEE) is a group of conditions characterized by the co-occurrence of epilepsy and intellectual disability (ID), typically with developmental plateauing or regression associated with frequent epileptiform activity. The cause of DEE remains unknown in the majority of cases. We performed whole-genome sequencing (WGS) in 197 individuals with unexplained DEE and pharmaco-resistant seizures and in their unaffected parents. We focused our attention on de novo mutations (DNMs) and identified candidate genes containing such variants. We sought to identify additional subjects with DNMs in these genes by performing targeted sequencing in another series of individuals with DEE and by mining various sequencing datasets. We also performed meta-analyses to document enrichment of DNMs in candidate genes by leveraging our WGS dataset with those of several DEE and ID series. By combining these strategies, we were able to provide a causal link between DEE and the following genes: NTRK2, GABRB2, CLTC, DHDDS, NUS1, RAB11A, GABBR2, and SNAP25. Overall, we established a molecular diagnosis in 63/197 (32%) individuals in our WGS series. The main cause of DEE in these individuals was de novo point mutations (53/63 solved cases), followed by inherited mutations (6/63 solved cases) and de novo CNVs (4/63 solved cases). De novo missense variants explained a larger proportion of individuals in our series than in other series that were primarily ascertained because of ID. Moreover, these DNMs were more frequently recurrent than those identified in ID series. These observations indicate that the genetic landscape of DEE might be different from that of ID without epilepsy.
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Encefalopatías/genética , Epilepsia/genética , Mutación/genética , Niño , Preescolar , Femenino , Genoma Humano/genética , Estudio de Asociación del Genoma Completo/métodos , Humanos , Discapacidad Intelectual/genética , Masculino , Recurrencia , Convulsiones/genéticaRESUMEN
The Inborn Errors of Metabolism Collaborative (IBEMC) includes clinicians from 29 institutions collecting data to enhance understanding of metabolic conditions diagnosable by newborn screening. Data collected includes hospitalizations, test results, services, and long-term outcomes. Through evaluation of this data, we sought to determine how frequently genetic counseling had been provided, how often genetic testing was performed, and also determine the consanguinity rate in this population. A data query was performed with the following elements abstracted/analyzed: current age, metabolic condition, whether genetic counseling was provided (and by whom), whether genetic testing was performed, and consanguinity. Genetic counseling was provided to families 95.8% of the time and in 68.6% of cases by a genetic counselor. Genetic testing was performed on 68.0% of subjects, with usage highest for fatty-acid-oxidation disorders (85.1%). The rate of consanguinity was 2.38%. Within this large national collaborative there is a high frequency of genetic counseling, though in one-third of cases a genetic counselor has not been involved. Additionally, while metabolic conditions have historically been diagnosed biochemically, there is currently high utilization of molecular testing suggesting DNA testing is being incorporated into diagnostic assessments - especially for fatty-acid-oxidation disorders where the underlying genotype helps predict clinical presentation.
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Consanguinidad , Asesoramiento Genético/estadística & datos numéricos , Pruebas Genéticas/estadística & datos numéricos , Errores Innatos del Metabolismo/diagnóstico , Tamizaje Neonatal/estadística & datos numéricos , Humanos , Recién Nacido , Masculino , Errores Innatos del Metabolismo/genéticaRESUMEN
Reimbursement for genetic counseling services was examined at a single institution. Patient encounters utilizing the 96040 CPT® code from 7/31/2009 through 7/31/2013 were reviewed. Exclusion criteria included billing records of patients seen by a physician the same day, self-pay, Medicaid, and Medicare patients. Of the 8,630 encounters with a genetic counselor, 582 encounters were eligible for review. Descriptive statistics (i.e., percentage of encounters receiving some level of reimbursement, average reimbursement rate, number of third party payors providing any level of reimbursement, and number of ICD-9 codes receiving any level of reimbursement) depicted reimbursement of the 96040 CPT® code for the encounters analyzed. Statistical analysis found a significant difference in reimbursement between third party payors that do and do not credential genetic counselors (p < .0001). There was no statistically significant difference between reimbursement rates for primary diagnostic ICD-9 codes when compared to primary diagnostic ICD-9 V codes used. Results will provide a useful baseline for local and national comparisons due to the paucity of data regarding CPT® 96040.
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Asesoramiento Genético/economía , Reembolso de Seguro de Salud/economía , Clasificación Internacional de Enfermedades/economía , Humanos , Estados UnidosRESUMEN
The SATB2-associated syndrome (SAS) was recently proposed as a clinically recognizable syndrome that results from deleterious alterations of the SATB2 gene in humans. Although interstitial deletions at 2q33 encompassing SATB2, either alone or contiguously with other genes, have been reported before, there is limited literature regarding intragenic mutations of this gene and the resulting phenotype. We describe five patients in whom whole exome sequencing identified five unique de novo mutations in the SATB2 gene (one splice site, one frameshift, and three nonsense mutations). The five patients had overlapping features that support the characteristic features of the SAS: intellectual disability with limited speech development and craniofacial abnormalities including cleft palate, dysmorphic features, and dental abnormalities. Furthermore, Patient 1 also had features not previously described that represent an expansion of the phenotype. Osteopenia was seen in two of the patients, suggesting that this finding could be added to the list of distinctive findings. We provide supporting evidence that analysis for deletions or point mutations in SATB2 should be considered in children with intellectual disability and severely impaired speech, cleft or high palate, teeth abnormalities, and osteopenia.