Recomendaciones de cuidados en salud de personas con síndrome de Down: 0 a 18 años / Recommendations for health care of people with Down syndrome from 0 to 18 years of age

People born with Down syndrome have an increased risk of birth defects and are more vulnerable to certain illnesses. Health care for them should emphasize prevention, early diagnosis and early treatment of their most common health conditions. A healthy lifestyle promotes future physical and intellectual development. The purpose of this review is to update health care recommendations for individuals with Down syndrome from 0 to 18 years ofage. The health professionals members involved in the care of these patients should be aware of these guidelines.

Conceptos básicos sobre el estudio de paternidad / Basic concepts about paternity testing

Nowadays, the analysis of genetic markers is a very important and validated tool for the identification of individuals, and for paternity testing. To do so, highly variable regions of the human genome are analyzed, making it possible to obtain the genetic profle of an individual, and to distinguish between different individuals. The methodology used is basically the same all over the world, consisting in the analysis of 13 to 15 markers. To assign biological paternity the child must have inherited the characteristics from the alleged father in each of the genetic markers analyzed. This analysis achieves a certainty higher than with any other test, which is expressed as the probability of paternity. This probability has to be at least 99.9 percent, but greater probabilities are usually obtained, especially if the mother is included in the analysis. If the characteristics of two or more genetic markers from the alleged father are absent in the child, biological paternity is excluded.

El análisis de marcadores genéticos se ha convertido en una herramienta muy importante y ampliamente reconocida para la identificación de individuos y para el estudio de paternidad. Para esto se estudian distintas regiones del genoma humano que son altamente variables en la población y que permiten obtener el perfil genético y distinguir entre distintos individuos. La metodología que se utiliza es básicamente la misma en todo el mundo y consiste en el análisis de entre 13 a 15 marcadores. La paternidad biológica se asigna cuando el hijo/a presenta las características que debe heredar del presunto padre en cada uno de los marcadores genéticos estudiados. A través de este análisis es posible asignar paternidad con un grado de certeza más alto que con cualquier otro sistema, el que se expresa como probabilidad de paternidad. Esta probabilidad debe alcanzar al menos 99,9 por ciento. Sin embargo, es posible obtener probabilidades mucho más altas, sobre todo si se incluye a la madre en el estudio. Si las características genéticas del supuesto padre están ausentes en el hijo/a en al menos dos marcadores, se excluye la paternidad biológica.

Caracterización clínico-genético-molecular de 45 pacientes chilenos con Síndrome de Prader Willi / Clinical, genetic and molecular features in 45 patients with Prader-Willi Syndrome

Background: Prader-Willi syndrome (PWS) is a neurogenetic disease characterized by neonatal hypotonia, retarded mental and motor development, hypogonadism, hyperphagia, morbid obesity and dysmorphic facial features. It has an incidence of 1:12.000-15.000 newborns and is caused by abnormalities in genes located in 15q11q13. PWS is one of the most frequent genetic disorders and microdeletion syndromes. It is also the most common cause of obesity from genetic origin and it was the first disease in which imprinting and uniparental disomy were recognized as cause of genetic disorders. Seventy to seventy five percent of PWS cases are due to 15q11q13 deletions, 20-25percent to uniparental disomy and 1percent to mutations in the imprinting center. Aim: To analyze the clinical, genetic and molecular features of patients with PWS, seen at one institution. Patients and methods: Retrospective review of 45 patients (27 males) with PWS seen at the Genetics Outpatient Clinic at INTA. Results: Twenty three (51.1percent) patients had a delection, 13 (28.9percent) patients did not have a deletion. In nine patients, fluorescence in situ hybridization (FISH) study was not performed, therefore the presence of deletion was unknown. The clinical score was 8 points for patients younger than 3 years (n=11) and 11.5 points for patients older than 3 years (n=34); for patients aged 12 months or less, the clinical score was 7 points. Mean clinical score was 11 points for patients with deletion and 10 points for patients without deletion. Conclusions: Most patients with PWS have a deletion; the phenotype depends on age and the clinical score is useful for Chilean patients with PWS .

Heterogeneidad de la presentación clínica del síndrome de microdeleción del cromosoma 22 región q11 / Clinical heterogenity of the chromosome 22q11 microdeletion syndrome

Background: DiGeorge anomaly, velocardiofacial syndrome and conotruncal anomaly face syndrome are part of a group of congenital malformations of the chromosome 22q11 microdeletion syndrome, since they share certain phenotypic features as well as a common genetic abnormality. The malformations include mild facial dysmorphic features, conotruncal heart defects, thymic and parathyroid hypoplasia or aplasia and cleft palate. Aim: To describe the initial clinical presentation of children with clinical and molecular diagnosis of 22q11 microdeletion. Patients and methods: Ten children (seven male) with the phenotypic features of 22q11 microdeletion syndrome are reported. Microdeletion was detected in peripheral Iymphocytes by fluorescent in situ hybridisation (FISH) with the TUPLE-1 DNA probe. Results: Two children had abnormal karyotypes, one of them had a visible deletion and another child had an unbalanced translocation inherited from his mother who had a balanced translocation between chromosomes 14 and 22. Two of the 10 patients had an anterior laryngeal web, a malformation infrequently described in this syndrome. Five patients had the diagnosis of DiGeorge anomaly, had a more serious clinical presentation and a higher early mortality. Conclusions: The high frequency of the 22q11 microdeletion syndrome, estimated at 1:5.000 newborns, and its variable presentations requires a high level of awareness for its early diagnosis and appropriate management of associated complications

Frecuencia de los defectos de cierre del tubo neural en las maternidades públicas de Santiago durante el año 1999 / Frequency of neural tube defects in Chilean maternity hospitals during 1999

Background: Fortification of wheat flour with folic acid in Chile, started in January 2000. This fortification should decrease the incidence of neural tube defects. Aim: To study the incidence of neural tube defects among Chilean newborns, during 1999. Material and methods : The records of all newborns and stillbirths with a birth weight over 500 g from 9 public maternity hospitals in Santiago in 1999, were reviewed. All neural tube defects, associated or not to other malformations were taken into account. Results: During the study period, 59.627 newborns and 455 stillbirths were analyzed. The global incidence of neural tube defects was 1.56 per 1.000 born (57 percent women, 42 percent men and 1percent ambiguous sex). Spina bifida was the most frequent neural tube defect found. Conclusion: These baseline data will be useful to assess the impact of folic acid fortification of wheat flour

Pesquisa molecular y clínica del síndrome de X-frágil en 300 pacientes con retardo mental inespecífico / Clinical and metabolic screening for fragile X syndrome in 300 patients with unspecific mental retardation

Background: Fragile X syndrome is the most freqent cause of mental retardation linked to the X chromosome. In the majority of cases, the mutation responsible for the syndrome is an expansion of the trinucleotide repeat (CGG)n, present in the 5' region of exon 1 of the gene for mental retardation associated with fragile X syndrome (FMR-1). Aim: To report the results of a fragile X screening in patients with mental retardation. Patients and methods: Fragile X screening using polymerase chain reaction methods was done in 386 X chromosomes from 300 patients (214 male), aged 4 to 26 years old. The modified Hagerman test was applied to male patients. Hybridization techniques were applied in a subgroup of 51 patients. Results: (CGG)n 30 was the allele found with the highest frequency in 50.2percent of patients. (CGG)n 29 was found in 29percent of patients. One subject had an allele with 46 CGG repeats, which corresponds to the gray zone. Hybridization studies were highly concordant with PCR, detecting four males with fragile X syndrome and a carrier female. The average clinical score of mental retardation not due to fragile X syndrome was 10.3 ñ 3.4 (range 3 to 23), and 97percent of males had a score below 19. The concordance between scores over 20 and molecular genotype was 98percent. Conclusions: The distribution of (CGG)n repeats, observed in this study, was significantly different to that previously reported for a normal Chilean population. The dispersion of molecular status and clinical score was lower than previously described using cytogenetic techniques

Síndrome hidroletalus: tres casos y su diagnóstico diferencial / Hydrolethalus syndrome: 3 cases and differential diagnosis

Se describen tres casos de síndrome de hidroletalus, dos en hermanos. El trastorno fue descrito inicialmente en finlandeses y ha sido reseñado pocas veces en personas de otros origenes. La anomalía es letal y se caracteriza por polihidroamnios severo, hidrocefalia, polidactilia y fisura labial y palatina, entre otros defectos. El diagnóstico es clínico. Se debe diferenciar de otros síndromes de la linea media como el orofaciodigital (IV y VI), Smith Lemli Opitz, Pallister Hall, Meckel, trisomia 13 y seudotrisomia 13. Se hereda en forma autosómica recesiva por lo que su identificación es muy importante para los efectos del consejo genético

Gonadoblastoma bilateral en una niña con isocromosoma 46, X, i (Y) (q10) / Bilateral gonadoblastoma in a girl with isochromosome 46, X, i (Y) (q10)

Niño de 6 años derivado por tallo bajo con micrognatia, paladar ojival, cuello alado, aréolas pequeñas y bajas, cúbito valgo, acortamiento del cuarto metacorpiano y escoliosis, que sugerían síndrome de Turner. En su cariotipo se identificó un isocromosoma del brazo largo del cromosoma Y: 46, X, i (Y) (qIO). En la ultrasonografía el útero tenía aspecto prepuberal y los ovarios no se identificaron. Se exploró mediante cirugía extirpando ambas gónadas, debido al riesgo de desarrollar un tumor gonadal dado la presencia de un cromosoma Y. En el examen histopatológico se encontraron esbozos de trompas y características de gonadoblastoma

Estudio citogenético de 663 parejas con problemas reproductivos / Cytogenetic study of 663 partners with reproductive problems

Las alteraciones cromosómicas son invocadas invariablemente como una de las causas que es necesario estudiar en primera instancia, cuando se desea establecer el diagnóstico etiológico de una pareja con problemas reproductivos. En este trabajo presentamos los resultados de 1326 exámenes citogenéticos correspondientes a 663 parejas con este tipo de problemas en un período de 17 años, en el cual se obtuvo un rendimiento del 9.2 por ciento, similar a otros reportes de la literatura. Las alteraciones estructurales más frecuentes fueron las translocaciones recíprocas, seguidas de las translocaciones robertsonianas, las inversiones y los mosaicos estructurales

Trisomía 8: reporte de cuatro casos / Chromosome 8 trisomy: report of 4 cases

La trisomía 8 es una anomalía cromosómica que en la mayoría de los casos descritos corresponde a un mosaico. Sus características clínicas varían desde dismorfias discretas hasta malformaciones severas que, por lo general, incluyen retardo mental -leve a grave-, dismorfias faciales típicas, alteraciones esqueléticas,pliegues palmares y plantares profundos,anomalías renales y otras. Con el propósto de ilustrar la variedad de las características fenotípicas de estas anomalías se describen los casos clínicos de cuatro pacientes cuyo diagnóstico se confirmó citogenéticamente, tres con trisomía en mosaico y uno con trisomía 8 completa. La solicitud del estudio citogenético tuvo su origen en la dismorfia, retrasa del desarrollo psicomotor o del lenguaje o hipotonía muscular esquelética. Es importante tener en cuenta la variedad de las caractrerísticas fenotípicas de esta trisomía, para sospechar correctamente el diagnóstico y solicitar oportunamente el estudio citogenético

Diagnóstico citogenético antenatal: indicaciones y experiencia del servicio de genética del hospital clínico Universidad de Chile / Prenatal cytogenetic diagnosis: indications and experience of the genetical service in clinical hospital of Universidad de Chile

El diagnóstico cromosómico antenatal por amniocentesis y cordocentesis se realiza desde hace 7 años en el Laboratorio de Citogenética del Hospital Clínico de la Universidad de Chile. Su principal utilidad reside en la complementación diagnóstica cuando se detecta un embarazo patológico y en la tranquilidad que le da un resultado normal a una mujer con temor de una cromosomopatía por edad materna avanzada. El hallazgo de una alteración cromosómica en líquido amniótico ha ocurrido en el 16,2 por ciento de los casos referidos por anomalías detectadas ecográficamente y sólo en el 5,0 por ciento de aquellos con edades mayores en la madre. Las cromosomopatías encontradas en sangre de cordón corresponden a un 18,2 por ciento. Es importante destacar que un resultado normal es igualmente relevante para las decisiones en el manejo pre y postnatal