Missed diagnosis or misdiagnosis: Common pitfalls in genetic testing

Genetic testing has the power to identify individuals with increased predisposition to disease, allowing individuals the opportunity to make informed management, treatment and reproductive decisions. As genomic medicine continues to be integrated into aspects of everyday patient care and the indications for genetic testing continue to expand, genetic services are increasingly being offered by non-genetic clinicians. The current complexities of genetic testing highlight the need to support and ensure non-genetic professionals are adequately equipped with the knowledge and skills to provide services. We describe a series of misdiagnosed/mismanaged cases, highlighting the common pitfalls in genetic testing to identify the knowledge gaps and where education and support is needed. We highlight that education focusing on differential diagnoses, test selection and result interpretation is needed. Collaboration and communication between genetic and non-genetic clinicians and integration of genetic counsellors into different medical settings are important. This will minimise the risks and maximise the benefits of genetic testing, ensuring adverse outcomes are mitigated.

Efectividad y aspectos éticos del asesoramiento genético en Cuba / Effectiveness and ethical aspects of genetic counseling in Cuba

Introducción: El asesoramiento genético constituye el proceso central en el manejo de trastornos de causa genética, de ahí la importancia de evaluar su efectividad. Objetivo: Evaluar la efectividad y aspectos éticos del asesoramiento genético en Cuba. Métodos: Se realizó un estudio observacional - descriptivo - retrospectivo de 2003 a 2013, que consistió en la realización de entrevistas, basadas en instrumentos diseñados y validados, a familias atendidas en los servicios de asesoramiento genético y a otros ciudadanos, la muestra quedó constituida por 13 142 individuos. Resultados: El nivel de conocimientos adquiridos fue bueno en 71,1 por ciento de los participantes; predominaron las decisiones muy racionales (68,4 por ciento); en 74,9 por ciento de las familias se logró un buen ajuste en relación con la situación particular. Existe en la población una elevada satisfacción con los servicios de asesoramiento genético (89,8 por ciento). La mayoría considera la prevención secundaria de enfermedades el objetivo más prioritario de la genética médica (81,3 por ciento), 93 por ciento está de acuerdo con el aborto selectivo como opción reproductiva ante el diagnóstico de enfermedades genéticas graves y de inicio precoz, y 76,5 por ciento prefiere el enfoque no directivo del asesoramiento genético. Conclusiones: El asesoramiento genético que se ofrece en los servicios de genética médica de Cuba es efectivo, satisface las expectativas de la población y cumple con principios éticos universalmente aceptados. La metodología diseñada y aplicada, basada en la organización de los servicios de genética en Cuba, permite la evaluación sistemática del asesoramiento genético, lo que propicia su mejoramiento y la posibilidad de trazar estrategias locales para aumentar su eficacia y alcanzar su excelencia(AU)

Introduction: Genetic counseling is the central process in the management of genetic disorders, hence the importance of assessing its effectiveness. Objective: Assess the effectiveness and ethical aspects of genetic counseling in Cuba. Methods: An observational - descriptive - retrospective study was conducted from 2003 to 2013, which consisted of conducting interviews based on instruments designed and validated with families assisted in genetic counseling services and other citizens; the sample consisted of 13 142 individuals. Results: The level of knowledge acquired was good in 71.1 percent of the participants; very rational decisions predominated (68.4 percent); in 74.9 percent of the families a good adjustment was achieved in relation to the particular situation. The population is highly satisfied with the genetic counselling services (89.8 percent). Most consider secondary diseases prevention to be the top priority for medical genetics (81.3 percent), 93 percent agree with selective abortion as a reproductive option after a diagnosis of serious and early-onset genetic diseases, and 76.5 percent prefer the non-directive approach to genetic counseling. Conclusions: The genetic counseling offered in the medical genetics services of Cuba is effective, satisfies the expectations of the population and complies with universally accepted ethical principles. The methodology designed and applied, based on the organization of genetic services in Cuba, allows the systematic assessment of genetic counseling, which males possible their improvement and the chance of devising local strategies to increase their effectiveness and achieve excellence in the service(AU)

Importance of Studying Older Siblings of Patients Identified by Newborn Screening: a Single-Center Experience in Mexico

Abstract Introduction: Any abnormal newborn screening (NBS) test should be subjected to appropriate diagnostic tests and should be followed. Once the newborn has been diagnosed and treated, the family should receive comprehensive genetic services. Aim: To present the experience of studying older siblings of patients with inborn errors of metabolism (IEM) identified by NBS in a single-national follow-up reference center. Methods: A retrospective analysis of medical files of the IEM patients detected by NBS was conducted. All those older siblings who tested positive for the same IEM of the patient detected by newborn screening were included. Results: A total of 26 positive siblings from 18 families with seven different IEM were found (phenylketonuria, argininemia, glucose-6-phosphate dehydrogenase deficiency, 3-methylcrotonyl-CoA carboxylase deficiency, dihydropteridine reductase deficiency, tyrosinemia type 3, and medium chain acyl-CoA dehydrogenase deficiency). The age range of the affected siblings was 2 to 19 years old, with a mean age of 8.5 years. Ten older siblings (38.5%) had clinical consequences for the disease, including severe intellectual disability. Conclusions: It is necessary to study older siblings, and family history and genetic counseling of all NBS-detected families should be recommended, especially in countries where expanded NBS programs are beginning.

Los servicios de genética médica en Venezuela / Medical genetics services in Venezuela / Serviços de genética médica na Venezuela

RESUMEN Objetivo. Caracterizar los servicios de genética médica de Venezuela con el fin de conocer la distribución de sus recursos, servicios, tecnologías y formación profesional. Métodos. Se realizó una investigación descriptiva, de tipo documental, entre febrero y noviembre de 2016 de los servicios de genética, mediante la revisión de fuentes documentales primarias y el uso de una ficha de recolección de datos en las instituciones de investigación para información referente a disponibilidad de recursos humanos, servicios de atención y diagnóstico, así como formación profesional, y la base de datos de la Sociedad Venezolana de Genética Humana, que permitió identificar los recursos humanos en centros de genética. El criterio de inclusión fue instituciones con recursos humanos formados en genética. Resultados. Los criterios fueron cumplidos por cuatro instituciones de investigación, siete universidades y cuatro hospitales, todos del sector público. En estas instituciones trabajan 124 profesionales, 56 son médicos y 68 se desempeñan en el área de laboratorio. Sesenta y dos por ciento de los profesionales pertenecen a las instituciones de investigación; estas cuentan con servicios de atención clínico, diagnóstico molecular, bioquímico y, con menos frecuencia, los análisis citogenéticos, prenatales y forenses. Cinco regiones del país tienen entre dos y cuatro médicos genetistas por millón de habitantes. El 96% de los profesionales de laboratorio se localizan en dos regiones (Capital y Zuliana), cinco regiones carecen de ellos. Las instituciones de investigación han formado en genética el 40% de los recursos humanos actuales del país. Conclusiones. Los servicios de genética presentan gran variabilidad de opciones diagnósticas, un acceso limitado y grandes aportes en formación profesional; se requieren políticas coordinadas que los integre y disminuya las brechas.

ABSTRACT Objective. To characterize medical genetics services in Venezuela and describe the distribution of their resources, services, technologies, and professional training. Methods. A descriptive, documentary study of genetic services was conducted between February and November 2016, involving a review of primary documentary sources and the use of a data collection form in research institutions to obtain information on the availability of human resources, clinical care, and diagnostic services, as well as professional training. Furthermore, the Venezuelan Society of Human Genetics database was used to identify the human resources available in genetics centers. The criterion for inclusion was being an institution with staff trained in genetics. Results. The inclusion criterion was met by four research institutions, seven universities, and four hospitals, all in the public sector. A total of 124 professionals work in these institutions; 56 of them are physicians and 68 are laboratory staff. Of these professionals, 62% are affiliated with research institutions, which offer patient care services, molecular and biochemical diagnostic services, and, more rarely, cytogenetic, prenatal, and forensic testing. Five regions of the country have between two and four physicians specializing in genetics per million inhabitants. Of the laboratory professionals, 96% are located in two regions (Capital and Zuliana); five regions have none. Research institutions have provided training in genetics to 40% of the country's current human resources. Conclusions. Genetics services show great variability in terms of diagnostic options. They train large numbers of professionals, but access is limited. There is a need for coordinated policies to integrate these services and reduce existing gaps.

RESUMO Objetivo. Caracterizar os serviços de genética médica da Venezuela com a finalidade de conhecer a distribuição dos recursos, prestação de serviços, tecnologias usadas e formação profissional nesta área. Métodos. Uma pesquisa descritiva documental dos serviços de genética médica foi realizada de fevereiro a novembro de 2016. Foi feita uma revisão das fontes documentais primárias nas instituições de pesquisa com o preenchimento de fichas de coleta de dados com informação sobre a disponibilidade de recursos humanos, prestação de serviços de atendimento e diagnóstico e formação profissional. Foi feita também uma revisão do banco de dados da Sociedade Venezuelana de Genética Humana para identificar os recursos humanos nos centros de genética. O critério de inclusão do estudo foi ser uma instituição com recursos humanos formados em genética. Resultados. Os critérios do estudo foram satisfeitos por 4 instituições de pesquisa, 7 universidades e 4 hospitais, todos da rede pública. Foram identificados 124 profissionais trabalhando nestas instituições: 56 médicos e 68 funcionários da área de laboratório. Sessenta e dois por cento dos profissionais pertencem a instituições de pesquisa que prestam serviços de atendimento clínico e diagnóstico molecular e bioquímico e, menos frequentemente, realizam análises citogenéticas, pré-natais e forenses. Cinco regiões do país têm entre 2 e 4 médicos geneticistas por milhão de habitantes. Além disso, 96% dos profissionais de laboratório estão distribuídos em 2 regiões (capital e Zuliana), sendo que não há nenhum profissional em 5 regiões. As instituições de pesquisa formam atualmente 40% dos recursos humanos em genética do país. Conclusões. Os serviços de genética médica são caracterizados por grande variabilidade nas opções diagnósticas, acesso limitado e grande contribuição para a formação profissional. Fazem-se necessárias políticas coordenadas para integrar e reduzir as lacunas.

Feasibility of introducing genetic services in the National Family Welfare Programme in India.

Background & objective: Genetic factors could play an important role in the outcome of pregnancy. This study was carried out to identify risk factors that result in adverse pregnancy outcome and to develop a system of screening and referral to a tertiary hospital equipped with facilities for diagnosis and management of such high risk pregnancies. Methods: District level hospitals close to the participating centers e.g. All India Institute of Medical Sciences, New Delhi, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, BJ Medical College, Pune, St. John Medical College, Bangalore and Genetic Research Center, (ICMR), Mumbai, were selected. Pregnant women < 28 wk gestation attending antenatal OPD of selected district hospitals were included. All eligible women who gave consent for participation in the study, were screened using a predesigned proforma based on family history, past pregnancy history, history of genetic disease/ congenital malformation in previous child and history of present pregnancy. Pregnancy outcome was noted. Results: There was statistically significant difference in the outcome of pregnancy in the following groups: (i) past pregnancy history of 3 or more spontaneous abortions (RR= 3.9; CI=1.17-9.02); (ii) still birth (RR= 2.5; CI= 1.41-4.48); (iii) previous child with neurol tube defect (NTD) (RR=2.3; CI= 1.22- 4.60); and (iv) previous child with congenital malformation (RR=2.2; CI = 1.11- 4.35). Interpretation & conclusion: A sample questionnaire may be used for screening of pregnant women at risk of having and adverse outcome. Also screening of pregnant women for thalassaemia carrier state and maternal serum α-foetoprotein (AFP) for NTD may be useful.

Capacitação em genética médica para residentes em medicina de família e comunidade: relato de experiência / Training in medical genetics for residents in family and community medicine: report of experience

Este trabalho é o relato de uma experiência de capacitação, vivenciado por um residente do segundo ano do Programa de Residência em Medicina de Família e Comunidade da Universidade Federal de São Carlos, no Ambulatório de Genética Médica. A capacitação teve duração total de 60 horas, sendo 40 horas de atividades clínicas no ambulatório e 20 horas de atividades teóricas. O objetivo era que o residente se apropriasse de alguns fundamentos teóricos da genética médica, a partir da constatação das suas implicações na prática clínica, tornando a aprendizagem significativa.O médico residente foi capacitado para conduzir os problemas genéticos comuns no nível da atenção primária à saúde, encaminhando para o especialista somente aqueles pacientes que requerem cuidados especiais em termos de diagnóstico, investigação e tratamento. Foram enfatizadas as ações de cuidado em saúde possíveis de serem realizadas na atenção primária, notadamente no sentido de prevenção de deficiência mental e de anomalias congênitas. Com esta experiência, espera-se ter contribuído para formação de um médico de família e comunidade mais competente na área da genética médica.

This work is the report of an experience of training, experienced by a resident of the second year of Family and Community Medicine Residency Program of the Federal University of São Carlos, in the Ambulatory of Medical Genetics. The training had total duration of 60 hours, and 40 hours of clinical activities in the ambulatory and 20 hours of theoretical activities. The goal was the resident take possession of theoretical foundations of some medical genetics, from the findings of its implications for clinical practice, making learning meaningful. The resident doctor has been trained to conduct the genetic problems common in the level of primary health care, forwarding to the specialist only those patients who require special care in terms of diagnosis, treatment and research. We emphasized the actions of a health care possible to be implemented in primary care, notably in order to prevent mental retardation and congenital anomalies. The authors expectation is the experience may contribute for formation of a community family physician more competent in the field of medical genetics.

Experience of medical genetics in Hong Kong / 北京大学学报(医学版)

As a geographically integral part of south China, the population mix of Hong Kong is largely influenced by itslocation. In the past150 years, its population has increased from a fewthousand to 5.7 million. This is the resultof episodic influxes of a great mass of people from China, often associated with political upheavals or economic cri-sis. It explains a population structure of95% Chinese. This structure is also reflected in the finding of genetic vari-ants in this population, which bears resemblance to neighbouring regions in China. For example, the thalassaemiasand lactose intolerance are common. However, the impact of migration from other parts of China cannot be neglec-ted, particulary for the last half century. This is evident from studies of glucose-6-phosphate dehydrogenase(G6PD) variants and other protein polymorphisms. The quick change in political situation has also promoted moreinflux of people from central and northern part of China. They bring with them a diversity of genetic constituent,mutations and diseases. However, as an international city, Hong Kong has significantinputfrommostethnic groupsin the world. Hence, the remaining 5% of its population is a heterogeneous group of minorities including Europe-ans, Indians, Japanese, and south-east Asians. Although their contribution to the cultural and economic growth inHong Kong is phenomenal, their impact on the genetic load is small. However, since their genetic makeup, andhence diseases, vary somewhatfromsouthern Chinese, they also poses specific needs to the provision of clinical ge-netic services.

Peking University Center of Medical Genetics (PUCMG): a comprehensive medical genetics program in China / 北京大学学报(医学版)

Medical genetics, as an important component in the advanced medical practice, has touched in variant aspectsof clinical aspects. Globally, in both developed and developing countries, medical genetics is playing more andmore important roles in dealing with the public healthcare. Being a medical specialty performing diagnosis and in-tervention for genetic disorders, the medical genetics has bridged the clinical practice and basic medical sciences.It is derived, butdifferent, fromhuman genetics. The difference of which is thatthe medical genetics provides clin-ical service for medical professionals and patients; however, the human genetics focuses on investigation of geneticprinciples.

Current genetic counseling in China / 北京大学学报(医学版)

In 1975, the American Society of Human Genetics adopted the following definition of genetic counseling: ge-netic counseling is a communication process which deals with the human problems associated with the occurrence orrisk of occurrence of a genetic disorder in a family. This definition indicates that genetic counseling is the deliveryof information about genetic diseases, including genetic risks, natural history of the disease, and clinical manage-ment of the disease, to patients and their families. Although genetic counseling is not a newword for both westerncountries and China, the development of which is quite different. Many excellent genetic counseling programs havebeen developed since then in developed countries, whereas there is no formal one in China. In the United States,professionals who carry outgenetic counseling musthave taken a professional training and have had the certificate ofAmerican Board of Genetic Counseling (ABGC) (www.abgc.net).

The prospect and current situation of prenatal diagnosis in mainland China / 北京大学学报(医学版)

1 The history and main problems in prenatal diagnosis and clinical diagnosis of inherited diseasesPrenatal diagnosis is to diagnose the fetal congenital defects and inherited diseases. In the earlier 1970s, thegroup of prenatal diagnosis in Peking Union Hospital was founded by Dr. Qiao-zhi LIN?Meanwhile, under the lead-ership of Dr. LIN, the group successfully completed the culture of amniotic fluid cells and began to diagnose fetalchromosomal diseases in the second trimester of pregnancy. In 1988, they succeeded in diagnosing chromosomaldiseases by taking the chorionic villus in the early pregnancy. Since then, the genetic and prenatal counseling tothose women who previously had children with severe defects were gradually developed. The work of the Peking U-nion Hospital developed prenatal diagnosis in our country. In 1990s, due to the unsettled problems about the posi-tion of technicians in prenatal and genetic disease diagnosis in medical institutions, the falling behind of standardtraining, the lost of person with proper ability, and the lack of standard criteria for some highly difficult techniquessuch as culturing amniotic fluid cell,the chorionic villus sampling,clinical diagnosis of chromosomal and geneticdiseases, medical friction appeared in some regions.At the same time, this type of clinical service, with difficulttechnique and high risk, is short of lawprotection, which reduced the enthusiasm of advanced clinical service. Inthe whole country, there is a shortage of persons with ability and clinical mature techniques?The Standardized crite-ria universally used in developed countries were not introduced to our country in time. The above factors leaded tothe lag-off on prenatal and genetic disease diagnosis in clinical service.