ABSTRACT
Introducción: La rama de genética de la Sociedad Chilena de Pediatría, en relación con el proyecto de ley que regula la despenalización de la interrupción voluntaria del embarazo en 3 causales, centrándose en la segunda causal que considera al «embrión o feto que padezca una alteración estructural congénita o genética incompatible con la vida extrauterina¼, se reunió para discutir conforme a la evidencia científica qué anomalías congénitas (AC) podrían ser incluidas en el proyecto de ley. Metodología: Los expertos en genética clínica se centraron en 10 AC. Se efectuó revisión bibliográfica y una reunión extraordinaria para discutirla. Resultados: Se acordó no emplear el término «incompatible con la vida extrauterina¼, pues existen excepciones de sobrevidas más prolongadas y cambiar por «anomalía congénita de mal pronóstico vital (ACMPV)¼. Se evaluaron 10 AC: defectos graves de cierre del tubo neural: anencefalia, iniencefalia y craneorraquisquisis, hipoplasia pulmonar, feto acardio, ectopia cordis, triploidía no mosaico, complejo limb body wall, anomalía body stalk, trisomía 13, trisomía 18 y agenesia renal bilateral. Se analizaron los hallazgos sobre prevalencia, historia natural, métodos diagnósticos prenatales, sobrevida, casos descritos de sobrevida prolongada. Para catalogarlas como ACMPV se consideraron: sobrevida posnatal, existencia de tratamientos y evolución posterior e historia natural sin intervenciones. Conclusión: Las ACMPV incluidas serían: anencefalia, hipoplasia pulmonar severa, feto acardio, ectopia cordis cervical, triploidía no mosaico, complejo limb body wall, anomalía body stalk, trisomía 13 no mosaico, trisomía 18 no mosaico y agenesia renal bilateral. Se requiere para el diagnóstico que toda mujer gestante tenga acceso a evaluaciones ecográficas de anatomía fetal, y en ocasiones a resonancia magnética y estudios citogenéticos y moleculares.
Introduction: The Genetic Branch of the Chilean Society of Paediatrics, given the draft Law governing the decriminalisation of abortion on three grounds, focusing on the second ground, which considers the "embryo or foetus suffering from a congenital structural anomaly or a genetic disorder incompatible with life outside the womb", met to discuss the scientific evidence according to which congenital anomalies (CA) may be included in this draft law. Methodology: Experts in clinical genetics focused on 10 CA, reviewed the literature evidence, and met to discuss it. Results: It was agreed not to use the term "incompatible with life outside the womb", as there are exceptions and longer survivals, and change to "congenital anomaly of poor prognosis (CAPP)". Ten CA were evaluated: serious defects of neural tube closure: anencephaly, iniencephaly and craniorachischisis, pulmonary hypoplasia, acardiac foetus, ectopia cordis, non-mosaic triploidy, "limb body wall" complex, "body stalk" anomaly, trisomy 13, trisomy 18, and bilateral renal agenesis. Findings on the prevalence, natural history, prenatal diagnostic methods, survival, and reported cases of prolonged survival were analysed. Post-natal survival, existence of treatments, and outcomes, as well as natural history without intervention, were taken into account in classifying a CA as a CAPP. Conclusion: A CAPP would be: anencephaly, severe pulmonary hypoplasia, acardiac foetus, cervical ectopia cordis, non-mosaic triploidy, limb body wall complex, body stalk anomaly, non-mosaic trisomy 13, non-mosaic trisomy 18, and bilateral renal agenesis. For their diagnosis, it is required that all pregnant women have access to assessments by foetal anatomy ultrasound and occasionally MRI, and cytogenetic and molecular testing.
Subject(s)
Humans , Female , Pregnancy , Prenatal Diagnosis/methods , Congenital Abnormalities/diagnosis , Abortion, Eugenic/legislation & jurisprudence , Prognosis , Congenital Abnormalities/physiopathology , Chile , Abortion, Legal/legislation & jurisprudence , ConsensusABSTRACT
Resumen. El Síndrome X Frágil (SXF) constituye la causa más frecuente de retraso mental hereditario y autismo. Los individuos con mutación completa (MC) presentan alteraciones clínicas que incluyen: déficit cognitivo y atencional, hiperactividad, autismo y problemas emocionales. Los portadores de premutación (PM) pueden afectarse del síndrome de temblor y ataxia asociado a X frágil (FXTAS); el 30 por ciento de las mujeres con PM presentan insuficiencia ovárica prematura(FXPOI). Cuando un individuo presenta una MC es frecuente encontrar otros familiares afectados. El fenotipo al nacer no es evidente, se sugiere que debe hacerse el diagnóstico entre los35-37 meses, sin embargo, la edad de diagnóstico en Chile es en promedio de 8 +/- 5.8 años. El centro de diagnóstico, tratamiento y seguimiento de pacientes con síndrome X frágil (CDTSXF)es un centro multidisciplinario, que incluye diagnósticos moleculares, genetistas médicos, asesoramiento genético, neurólogos, terapeutas ocupacionales, fonoaudiólogo, evaluaciones nutricionales y psicológicas para las familias afectadas. Desde el año 2010 hemos asistido a 28familias y detectado un número significativo de afectados debido a la detección en cascada. Se ha diagnosticado a 63 probandos, 57 MC y ocho mosaicos de MC/PM. Entre las madres portadoras 37 son PM y dos presentaron una MC. En 9/28 familias había un adulto mayor con FXTAS, diez familias presentaron mujeres con FXPOI. 41/63 probandos han participado denle el protocolo multidisciplinario del CDTSXF. Los resultados de este enfoque multidisciplinario nos motiva a seguir trabajando en mejorar el comportamiento y desarrollo cognitivo de los pacientes y atender las principales necesidades de las familias afectadas.
Fragile X Syndrome (FXS) is the most common inherited form of mental retardation and a leading known cause of autism. Individuals with a full mutation (FM) present disabilities including: cognitive and attention deficit, hyperactivity, autism, and other emotional problems. Carriers of a premutation (PM) may be affected by fragile X associated tremor/ataxia syndrome (FXTAS) and primary ovarian insufficiency (FXPOI) in 30 percent of PM women. Therefore, multigenerational family involvement is commonly found when a proband is diagnosed with a FXS mutation. FXS has no obvious phenotype at birth, it is suggested that the diagnosis should be made at 35-37 months; the age of diagnosis in Chile is on average 8+/-5.8 yo. The center for diagnosis, treatment and monitoring of patients with fragile X syndrome (CDTTRABAJOMFXS), is a multidisciplinary center that includes molecular testing, medical geneticists, genetic counseling, neurologists, occupational therapists, physical therapists, and nutritional and psychological interventions to families with an FM proband. Since 2010, we have assisted 28 families with a total of 63 diagnosed probands using specific PCR and Southern blot tests. Among them, 57 had a FM and eight had a mosaic FM/PM. Among the mothers 37 are PM carriers and two presented a FM. An older adult with FXTAS was present in 9/28 families; ten families presented women with FXPOI. A significant number of affected family members have been detected through cascade screening. Among the probands 41 of 63 have received some of the multidisciplinary diagnostic and interventions. The results of this multidisciplinary work allow us to put forward more effort towards improving behavior and cognitive development of patients as well as trying to solve families main needs.
Subject(s)
Humans , Male , Female , Child , Patient Care Team , Fragile X Syndrome/diagnosis , Fragile X Syndrome/therapy , Clinical Protocols , Cognition Disorders , Early Intervention, Educational , Fragile X Mental Retardation Protein , Language Disorders , Mutation , Nutritional Status , Occupational Therapy , Speech, Language and Hearing Sciences , Fragile X Syndrome/geneticsABSTRACT
Background: About 30 percent of cases of colon cancer (CC) have a family history of CC, and only 5 percent are hereditary forms. Hereditary forms have an increased risk of CC and other tumors. Aim: To report the molecular and genetic study in two families with hereditary CC. Material and Methods: Molecular analysis of the adenomatous polyposis coli (APC) gene of familial adenomatous polyposis (FAP), was done in a patient with multiple benign polyps and his children. Molecular analysis was performed for MLH1 gene mutation of hereditary non-polyposis colon cancer (HNPCC) in an asymptomatic patient with family history of multiple cancers and his mother with a confrmed mutation in the MLH1 gene. Results: The patient with FAP had an insertion of 17 base pairs in exon 9 of the APC gene and two of his children had the same mutation. The patient with history of HNPCC did not have the family mutation on MLH1. Conclusions: In the case of FAP, molecular study was performed in his children since manifestations in carriers of the mutation may begin in childhood. If the second patient would have had the mutation, the study of his children could have been postponed until the age of 18, when the risk for CC is increased.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Adenomatous Polyposis Coli/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Pedigree , Chile , Mutation , Risk FactorsABSTRACT
Microdeletion 22q11 in humans causes velocardiofacial and DiGeorge syndromes. Most patients share a common 3Mb deletion, but the clinical manifestations are very heterogeneous. Congenital heart disease is present in 50-80 percent of patients and is a significant cause of morbidity and mortality. The phenotypic variability suggests the presence of modifiers. Polymorphisms in the VEGFA gene, coding for the vascular endothelial growth factor A, have been associated with non-syndromic congenital heart disease, as well as with the presence of cardiovascular anomalies in patients with microdeletion 22q11. We evaluated the association of VEGFA polymorphisms c.-2578C>A (rs699947), c.-1154G>A (rs1570360) and c.-634C>G (rs2010963) with congenital heart disease in Chilean patients with microdeletion 22q11. The study was performed using case-control and family-based association designs. We evaluated 122 patients with microdeletion 22q11 and known anatomy of the heart and great vessels, and their parents. Half the patients had congenital heart disease. We obtained no evidence of association by either method of analysis. Our results provide further evidence of the incomplete penetrance of the cardiovascular phenotype of microdeletion 22ql 1, but do not support association between VEGFA promoter polymorphisms and the presence of congenital heart disease in Chilean patients with this syndrome.
Subject(s)
Adolescent , Adult , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Young Adult , DiGeorge Syndrome/genetics , Heart Defects, Congenital/genetics , Polymorphism, Genetic/genetics , Vascular Endothelial Growth Factor A/genetics , DiGeorge Syndrome/complications , Family , Gene Frequency , Haplotypes , Heart Defects, Congenital/etiology , Young AdultABSTRACT
Background: Mutations of the MSX1 gene may contribute to nonsyndromic forms of cleft lip and/or cleft palate. Aim: To search for mutations of MSX1 coding regions, including one highly conserved non-coding region in the single intron, among Chilean patients with cleft lip/palate. Patients and Methods: We studied 45 patients with cleft lip/palate and their parents. Oral mucosa samples were obtained with a swab. DNA was extracted and amplified by PCR. Results: Two missense mutations (G16D and G34A) were identified in this study that may be useful for future admixture studies. The G16D mutation appears to disrupt a possible splicing site and may contribute to clefting in this population. Conclusions: Rare MSX1 mutations are found in some cases of cleft lip and/or cleft palate but others remain to be found most likely in other regulatory regions of the gene.