[Neurodevelopmental (fragile X syndrome) and neurodegenerative (tremor/ataxia syndrome) disorders associated to the 'growth' of a gene]. / Trastornos del neurodesarrollo (síndrome X frágil) y neurodegenerativos (síndrome de temblor/ataxia) asociados al 'crecimiento' de un gen.

AIM: To present the latest findings on fragile X syndrome, the first genetic disorder identified to be caused by a new type of mutation called trinucleotide repeat expansion. DEVELOPMENT: Fragile X syndrome is the most common form of inherited mental retardation, is caused by hyperexpansion and hypermethylation of a CGG repeat tract in the FMR1 gene. In the first section we will discuss the various aspects of the gene mutation and the gene product, its phenotypic consequences in mutation carriers, diagnostic methodology, epidemiology, prevention, treatment and situation in Costa Rica. The second section deals with the recent findings in relation to the very recently described fragile X premutation tremor/ataxia syndrome, a neurodegenerative disorder affecting carriers of the mutation. CONCLUSIONS: Screening for the gene premutation in aged individuals who have tremor and balance problems is important, especially when accompanied by other signs such as parkinsonism, short term memory loss and dementia. Family genetic counselling can help those affected as well as future generations which may inherit fragile X syndrome.

Trastornos del neurodesarrollo (síndrome X frágil) y neurodegenerativos (síndrome de temblor/ataxia) asociados al 'crecimiento' de un gen / Neurodevelopmental (fragile X syndrome) and neurodegenerative (tremor/ataxia syndrome) disorders associated to the 'growth' of a gene

Objetivos. Presentar los últimos hallazgos acerca del síndrome del cromosoma X frágil, el primer trastorno genético identificado causado por un nuevo tipo de mutación llamado expansión de trinucleótidos repetidos. Desarrollo. El síndrome del cromosoma X frágil es la causa más común de retraso mental hereditario; lo causa el aumento de la expansión y de la metilación de un segmento de repeticiones CGG en el gen FMR1. En la primera sección discutiremos varios aspectos de la mutación y del producto génico, sus consecuencias fenotípicas en los afectados con la mutación, la metodología diagnóstica, la epidemiología, la prevención, el tratamiento y la situación en Costa Rica. En la segunda sección nos referiremos al recientemente descrito síndrome premutación X frágil con temblor/ataxia, un trastorno neurodegenerativo que afecta a los portadores de la mutación. Conclusiones. Es importante hacer una criba de la premutación del gen en adultos mayores con temblor y problemas de equilibrio, especialmente cuando se acompaña de otros signos como parkinsonismo, pérdida de memoria y demencia. El asesoramiento genético a la familia puede ser útil para los afectados y para las generaciones futuras que pueden heredar el síndrome del cromosoma X frágil

Aim. To present the latest findings on fragile X syndrome, the first genetic disorder identified to be caused by a new type of mutation called trinucleotide repeat expansion. Development. Fragile X syndrome is the most common form of inherited mental retardation, is caused by hyperexpansion and hypermethylation of a CGG repeat tract in the FMR1 gene. In the first section we will discuss the various aspects of the gene mutation and the gene product, its phenotypic consequences in mutation carriers, diagnostic methodology, epidemiology, prevention, treatment and situation in Costa Rica. The second section deals with the recent findings in relation to the very recently described fragile X premutation tremor/ataxia syndrome, a neurodegenerative disorder affecting carriers of the mutation. Conclusions. Screening for the gene premutation in aged individuals who have tremor and balance problems is important, especially when accompanied by other signs such as parkinsonism, short term memory loss and dementia. Family genetic counselling can help those affected as well as future generations which may inherit fragile X syndrome

Cordocentesis para diagnóstico fetal citogenético en Costa Rica / Cordocentesis for cytogenetic fetal diagnosis in Costa Rica

El objetivo de este estudio fue identificar cromosomopatía fetal en voluntarias con embarazos de alto riesgo genético, brindar adecuada atención obstétrica y pediátrica y asesoramiento genético. Desde el año 1992 hasta el 2001 inclusive se estudiaron 103 embarazos mediante cordocentesis y cariotipo fetal. La indicación en todos los casos excepto cinco fue examen ultrasonográfico anormal, ya sea porque éste detectó al menos una malformación fetal, poli-oligoamnios, retardo simétrico del crecimiento intrauterino, marcadores sonográficos de cromosomopatía, higroma quístico o hidropesía fetal. Las cordocentesis se realizaron desde la semana 15 hasta la semana 38 de aestación. Para los análisis citogenéticos se utilizaron preparaciones cromosómicas con bandas G, el nivel de resolución fue de 300-400 bandas y se estudiaron 20 figuras mitóticas por caso en promedio. El cariotipo se obtuvo en 90 casos; fue normal en 76 embarazos y anormal en 14, a saber: trisomía 18 en ocho casos, trisomía 13 en dos fetos y un caso cada uno de 45,X (síndrome de Turner), 92,XXYY (tetraploidía), 46,XY,der21 (cromosoma 21 anormal) y 46,XX,t(8;21)mat (translocación heredada de la madre). El diagnóstico prenatal de cromosomopatía permitió el asesoramiento genético y el manejo obstétrico y pediátrico de los casos de manera adecuada. En los embarazos con cariotipo normal esta información alivió la preocupación de muchos de los padres (AU)

[Cytogenetical prenatal diagnosis by amniocentesis during the II and III gestation trimesters in Costa Rica]. / Diagnóstico prenatal citogenético mediante amniocentesis durante los trimestres II y III de gestación en Costa Rica.

The identification of fetal abnormal chromosomes in high risk pregnancies allows proper pediatric and obstetric management of the cases as well as genetic counseling. The results of 842 genetic amniocentesis from 1986 to 1999 are reported. All procedures were performed transabdominally and under ultrasound guidance, in hospitals of the social security system and in private facilities. There were two main reasons for referral: abnormal ultrasound assessment (48% of cases) and advanced maternal age (35%). Most procedures (66%) were performed during the second trimester of pregnancy and 34% during the third trimester. Fetal cells were closed cultured and suspension harvested. Median turn around time was 14 days. In 217 amniotic fluid samples no diagnosis could be obtained, mainly due to absence of cell growth in late gestation samples or because of blood contamination. Of 625 fetal karyotypes 55 (9%) were abnormal, due to 33 trisomies (including a Robertsonian translocation trisomy 13), eight cases of monosomy X, three mosaics (including a mosaic trisomy 22), balanced and unbalanced translocations, extra structurally abnormal chromosomes and other defects. Pseudomosaicism was detected in five cases. Taking into account the reason for referral, cases studied as a result of abnormal ultrasound assessment exhibited 17% abnormal karyotypes, in contrast to 2.5% cytogenetic defects in pregnancies of women 35 years or older. Prenatal cytogenetic and sonographic findings correlated with the phenotype of the newborn in 211 cases available for follow-up. Prenatal diagnosis of fetal defects allowed genetic counseling as well as better obstetric management and pediatric care. Normal results of both tests provided reassurance to prospective parents.

[Karyotyping of fetal cells in the prenatal diagnosis in Costa Rica]. / Cariotipo de células fetales en el diagnóstico prenatal en Costa Rica.

The results of 182 genetic amniocenteses between 14 and 37 weeks gestation, from 1986 to 1992, and of two cordocenteses in 1992, are reported. There were two main reasons for referral: maternal age 35 years and older and abnormal ultrasound assessment. Fetal cells were closed cultured and mass harvested. In 3.7% of cases fetal chromosomes were defective. Turn around time was about three weeks up to and including 1991 and two weeks in 1992, culture failure rate was 7% that year. No cytogenetic misdiagnosis and no complication or sequelae related to the amniocenteses were detected. We conclude this is a safe and reliable procedure to obtain fetal karyotypes and to improve obstetric management of high-risk pregnancies.

[Chromosomic characteristics associated with leukemia and other hemopathies in Costa Rica]. / Características cromosómicas asociadas con leucemias y otras hematopatías en Costa Rica.

Chromosome analyses were performed on bone marrow and peripheral blood leucocytes of 117 patients with acute and chronic leukemias and myelodysplastic, myeloproliferative and hypereosinophilic syndromes, diagnosed in a Costa Rican hospital from May 1990 to July 1992. Cytogenetic diagnosis was achieved in 69.5% of the 131 samples, the karyotype was normal in half of them. The most common chromosomal defect was the Philadelphia translocation, found in 80.5% of the patients with chronic myelocitic leukemia as referral diagnosis and in some other cases. Other primary and secondary chromosomal abnormalities were less frequent. The karyotype analysis proved useful in clinical evaluation and management.