RESUMEN
OBJECTIVE: To establish the role of clinical and laboratory investigation of the cardiovascular system in children with Down's syndrome. DESIGN: Prospective evaluation; examiners blinded to results of laboratory studies. SETTING: Tertiary pediatric referral centre. PATIENTS: Fifty consecutive children with Down's syndrome presenting to a regional genetic centre. Children less than six weeks of age or with known heart disease were excluded. MEASURES: Following independent examinations by a geneticist and a pediatric cardiologist, an electrocardiogram (ECG) and two-dimensional and Doppler echocardiograms were carried out. RESULTS: Assessment by the geneticist yielded two false positives and five false negatives (sensitivity 67%, specificity 88%). Addition of an ECG to clinical evaluation increased the sensitivity to 80% and specificity to 90%, a rate comparable with clinical assessment by a cardiologist. No lesion requiring surgical correction was missed by this combination. CONCLUSIONS: Where expertise in pediatric echocardiography is not readily available, careful clinical assessment coupled with the interpretation of an ECG is adequate and appropriate screening of the child with Down's syndrome.
Asunto(s)
Síndrome de Down/complicaciones , Cardiopatías Congénitas/diagnóstico , Ecocardiografía , Ecocardiografía Doppler , Electrocardiografía , Cardiopatías Congénitas/complicaciones , Humanos , Lactante , Estudios Prospectivos , Sensibilidad y EspecificidadAsunto(s)
Pruebas Genéticas , Genética Médica , Canadá , Niño , Medicina Familiar y Comunitaria , Femenino , Asesoramiento Genético , Terapia Genética , Humanos , MasculinoRESUMEN
A pilot project of maternal serum alpha-fetoprotein (MSAFP) screening was carried out in Ontario from 1982 to 1985 to examine the feasibility and acceptability of screening a prenatal population for open fetal neural tube defects. A total of 8140 patients at low genetic risk were screened. Patient acceptance was excellent. Blood samples were taken at 16 to 18 weeks' gestation. If the MSAFP level was elevated, the assay was repeated and an ultrasound examination performed. Amniocentesis was offered to 67 women with unexplained persistently elevated levels. The outcome of pregnancy was known in 7473 patients (91.8%). Seven of nine known open fetal neural tube defects were detected. All were confirmed, and no unaffected fetuses were aborted on the basis of the screening results. The rates of perinatal death (6.7%), intrauterine growth retardation (11.7%) and prematurity (23.3%) were significantly higher among the patients with unexplained elevated MSAFP levels than among those with normal levels (p less than 0.001). Of 20 patients with unexplained low levels, 10 subsequently had spontaneous abortions and 10 gave birth to term appropriate-for-gestational-age infants. Seven of nine patients who gave birth to infants with autosomal trisomy had MSAFP values below the median. The findings indicate that MSAFP screening is feasible, accurate and acceptable in a low-risk area.
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Tamizaje Masivo/métodos , Diagnóstico Prenatal/métodos , alfa-Fetoproteínas/análisis , Aborto Espontáneo/epidemiología , Femenino , Muerte Fetal/epidemiología , Humanos , Mortalidad Infantil , Defectos del Tubo Neural/epidemiología , Ontario , Aceptación de la Atención de Salud , Proyectos Piloto , Embarazo , Embarazo Múltiple , Radioinmunoensayo/métodos , GemelosRESUMEN
The program DUCHEN calculates the probability that a woman is a carrier of an X-linked, lethal recessive disease on the basis of information in the woman's family and any available biochemical data. It is easily used by persons without computer knowledge or experience. The present version can accommodate families consisting of up to 100 people in seven generations. Risks may be estimated on the basis of pedigree information only, or with the inclusion of one or more types of biochemical test results. Biochemical data are incorporated with pedigree information into final risks using the powerful statistical technique of logistic discrimination, a procedure particularly suited for the separation of non-normal populations on the basis of overlapping quantitative characteristics. Mutation rates are specified separately for males and females. DUCHEN is available in FORTRAN 77, IBM BASIC, and Applesoft BASIC, and may be used on a variety of mainframe or microcomputers. The model was used to calculate risks for 375 girls and women in 46 families with Duchenne muscular dystrophy (DMD); serum creatine kinase tests had been carried out on 167 of these subjects who were of reproductive age. Carrier probabilities equal to or lower than the population risk (0.0004) were obtained for 21% of the aunts and 43% of the cousins of affected boys from families with an isolated case of DMD and for 14% of the cousins of affected boys from families with a known DMD history. DUCHEN should assist counsellors in determining which members of large families should be further examined using either standard biochemical carrier detection methods or DNA marker studies.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Tamización de Portadores Genéticos/métodos , Distrofias Musculares/genética , Programas Informáticos , Creatina Quinasa/sangre , Femenino , Genes Recesivos , Asesoramiento Genético , Ligamiento Genético , Humanos , Masculino , Modelos Genéticos , Distrofias Musculares/enzimología , Linaje , Riesgo , Cromosoma XRESUMEN
Genetic counselling of two younger sisters of a 32-year-old man with a 28-year history of severe progressive muscular dystrophy stimulated efforts to determine his diagnosis and the mode of inheritance. The investigation was complicated by the patient's sudden death during the period of investigation. However, genetic and neurological evaluation, electromyography and nerve conduction studies, serum enzymes and reinterpretation of a muscle biopsy 23 years earlier made it unlikely that inheritance was X-linked, thereby substantially reducing his sisters' risk of bearing affected children. Precise diagnosis, especially of what is not likely in atypically presenting genetic disease, is of paramount importance in managing families at risk for genetic disease in future children. It is an important responsibility of family physicians concerned with preventive genetic medicine.
RESUMEN
Partial Trisomy- 9q was observed in an infant with a multiple malformation syndrome who survived to 18 months. Cytogenetic investigations stimulated by the family history of similarly affected individuals revealed a translocation, t(9;16)(q32;q24), identifiable in four generations of the proband's family. A review of our cases with those reported in the literature reveals clinical similarities. This report sets forth a clinical description of the characteristic phenotype of the 9q partial Trisomy syndrome, including findings at post-mortem, documents multigeneration transmission and discusses this syndrome's clinical overlap with other malformation syndromes.
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Anomalías Múltiples/genética , Aberraciones Cromosómicas , Cromosomas Humanos 16-18 , Cromosomas Humanos 6-12 y X , Padre , Humanos , Recién Nacido , Cariotipificación , Masculino , Linaje , Translocación Genética , TrisomíaRESUMEN
The result of a previous study showing an association between mental development and fragile X activity in heterozygous females is given further support by similar investigations of three additional kindreds. The increased frequency of demonstrable fragile X chromosomes in mentally retarded females appears to be due to an increase in the active fragile X while the inactive marker X remains at a similar low frequency in all heterozygotes whether retarded or not. The frequencies of the active fragile X separated the normal and abnormal subjects into two distinct populations. The suggested inverse correlation between the number of lymphocytes with detectable fragile X chromosomes and advancing age can be attributed to ascertainment biases.
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Síndrome del Cromosoma X Frágil/genética , Heterocigoto , Aberraciones Cromosómicas Sexuales/genética , Adolescente , Adulto , Factores de Edad , Anciano , Niño , Compensación de Dosificación (Genética) , Femenino , Humanos , Inteligencia , Masculino , Persona de Mediana Edad , Ontario , Linaje , Factores SexualesRESUMEN
The results of the present investigation have failed to confirm the suggestion that there is a significant increase in the proportion of echinocytes in preparation of fresh erythrocytes in patients with Duchenne muscular dystrophy and heterozygous carriers of this disorder.
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Eritrocitos Anormales , Distrofias Musculares/sangre , Cromosomas Sexuales , Cromosoma X , Recuento de Eritrocitos , Femenino , Heterocigoto , Humanos , Masculino , Distrofias Musculares/diagnóstico , Distrofias Musculares/genéticaAsunto(s)
Dextrocardia/genética , Angiocardiografía , Animales , Cateterismo Cardíaco , Dextrocardia/complicaciones , Dextrocardia/diagnóstico , Conducto Arterioso Permeable/complicaciones , Conducto Arterioso Permeable/genética , Electrocardiografía , Auscultación Cardíaca , Defectos del Tabique Interventricular/complicaciones , Defectos del Tabique Interventricular/genética , Masculino , Linaje , Radiografía TorácicaRESUMEN
Genetic counselling is the single most important service which family physicians can render in the area of genetic medicine. The rationale, procedures and effectiveness of genetic counselling are discussed, especially in relation to prenatal diagnosis of genetic disease.
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Síndrome de Klinefelter/genética , Síndrome de Turner/genética , Aborto Espontáneo , Adolescente , Adulto , Antígenos de Grupos Sanguíneos , Defectos de la Visión Cromática/genética , Femenino , Muerte Fetal , Humanos , Masculino , Edad Materna , Linaje , Embarazo , Cromatina Sexual , Razón de Masculinidad , GemelosRESUMEN
Suggestions for improvement of the educational program in the first two years of the medical curriculum are made in the light of simultaneous experiences as teacher and student. The learning needs of the student should be given more consideration. Many of the present learning-teaching problems could be solved by closer communication and collaboration between instructors teaching the same students coupled to an official recognition of the value of good teaching. In spite of a multiplicity of courses and basic science departments, the student is a single person with a rather limited goal. He is required to learn and remember a vast amount of detailed factual information during his first two years of the medical curriculum. The medical student should be reinstated as an integral human component of the structure and functioning of each department. This is a difficult task because the dual functions of research in a specialized discipline and undergraduate medical teaching frequently pull an individual's or department's activities in opposite directions and lead to administrative problems.