Carolina Isaza

Sirenomelia and cyclopia cluster in Cali, Colombia†

Sirenomelia and cyclopia share etiologic and pathogenic characteristics. A cluster of these two patterns of malformation in the city of Cali, Colombia, is described. Four sirenomelia and four cyclopia cases were born within a 165 days period in one hospital in Cali. The lapse between conception dates of first and last cases was shorter for sirenomelia (53 days) than for cyclopia (231 days). Based on ECLAMC (Latin American Collaborative Study of Congenital Malformations) published data, the observed/expected ratio (5.7) for both defects is statistically significant (P < 0.001). Mothers residence during the first trimester of pregnancy is concentrated in a same city quarter for four of the eight cases, close to a know polluting active landfill, and the other four cases, along the Cauca river, downstream from this landfill. Birth prevalence rates for two sentinel anomalies, that is, anal and esophageal atresia for sirenomelia and oral clefts for DeMyer holoprosencephaly spectra, were not higher in Cali than in the rest of ECLAMC material. The Computer Assisted Telephone Interviewing was applied to mothers of the 8 patients, and 32 matched controls. Seven of 295 variables were associated with sirenomelia, 3 of them related to house tap water, one to exposure to street drugs, one to physical injury, and 2 secondary to abnormal pregnancy outcome. None was associated with cyclopia. Results from hair dosage of heavy metals in the 8 patients mothers were inconsistent. The time‐space cluster is nonrandom for sirenomelia, and possibly random for cyclopia. The polluting landfill remains as a possible etiological factor.

Clusters of sirenomelia in South America

BACKGROUND One hospital in the city of Cali, Colombia, of the ECLAMC (Latin-American Collaborative Study of Congenital Malformations) network, reported the unusual occurrence of four cases of sirenomelia within a 55-day period. METHODS An ECLAMC routine for cluster evaluation (RUMOR) was followed that included: calculations of observed/expected ratios, site visits, comparison with comprehensively collected local, South American, and worldwide data, cluster analysis, and search for risk factors. RESULTS All four Cali sirenomelia cases were born to mothers living in a 2 km(2) area, in neighboring communes, within the municipality of Cali. Considering the total births of the city of Cali as the denominator, and based on ECLAMC baseline birth prevalence rates (per 100,000) for sirenomelia (2.25, 95% CI: 2.66, 3.80), the cluster for this congenital abnormality was unlikely to have occurred by chance (observed/expected ratio = 5.77; 95% CI: 1.57-14.78; p = .002). No consistent common factor was identified, but vicinity to an open landfill as the cause could not be rejected. Another ECLAMC hospital in San Justo, Buenos Aires, Argentina, reported three further cases but these did not seem to constitute a nonrandom cluster. CONCLUSIONS The methodology used to evaluate the two possible clusters of sirenomelia determined that the Cali sirenomelia cluster was unlikely to have occurred by chance whereas the sirenomelia cluster from San Justo seemed to be random.

Defectos Congénitos Mayores en un Hospital de Tercer Nivel en Cali - Colombia. 2004 – 2008

Objetivos Determinar la prevalencia de los defectos congenitos diagnosticados al nacimiento y describir los factores sociodemograficos y del recien nacido asociados a la ocurrencia de estas patologias en un hospital de tercer nivel de la ciudad de Cali en Colombia. Metodologia Se analizo la informacion del sistema de vigilancia del Hospital Universitario del Valle entre marzo de 2004 y octubre de 2008. Para determinar la ocurrencia de defectos congenitos se siguio la metodologia propuesta por el ECLAMC. Se realizaron tablas y graficos para describir las caracteristicas de los recien nacidos y sus padres. Resultados Durante el periodo de estudio, un total de 4 anos y 7 meses entre 2004 y 2008, se atendieron 32 995 nacimientos, de los cuales 735 presentaron al menos un defecto congenito, para una prevalencia de 2,22 por 10 000 nacimientos. Por grupos especificos de defectos congenitos se registraron las prevalencias mas altas (casos x 10 000 nacimientos) para: polidactilia (22,1), pie equinovaro (17,6), hidrocefalia (16,4), defectos del tubo neural (16,7), defectos por reduccion de extremidades (8,2), labio y/o paladar hendido (10,9), cardiopatias (14,6), hidronefrosis (11,5), gastrosquisis (7,3), ciclopia (2,4) y sirenomelia (1,2). Discusion Las prevalencias de defectos congenitos relacionados con factores ambientales como hidrocefalia, defectos por reduccion de extremidades, pie equino varo, hidronefrosis, gastrosquisis, ciclopia y sirenomelia presentaron prevalencias mas altas en comparacion con lo reportado en la literatura. Se presentan algunas hipotesis que podrian explicar el aumento registrado.

Phenobarbital use and neurological problems in FMR1 premutation carriers.

Fragile X Syndrome (FXS) is a neurodevelopmental disorder caused by a CGG expansion in the FMR1 gene located at Xq27.3. Patients with the premutation in FMR1 present specific clinical problems associated with the number of CGG repeats (55-200 CGG repeats). Premutation carriers have elevated FMR1 mRNA expression levels, which have been associated with neurotoxicity potentially causing neurodevelopmental problems or neurological problems associated with aging. However, cognitive impairments or neurological problems may also be related to increased vulnerability of premutation carriers to neurotoxicants, including phenobarbital. Here we present a study of three sisters with the premutation who were exposed differentially to phenobarbital therapy throughout their lives, allowing us to compare the neurological effects of this drug in these patients.

A new mutation of the PCNT gene in a Colombian patient with microcephalic osteodysplastic primordial dwarfism type II: a case report

IntroductionMicrocephalic osteodysplastic primordial dwarfism is a syndrome characterized by the presence of intrauterine growth restriction, post-natal growth deficiency and microcephaly. Microcephalic osteodysplastic primordial dwarfism type II is the most distinctive syndrome in this group of entities. Individuals affected by this disease present at an adult height of less than 100cm, a post-pubertal head circumference of 40cm or less, mild mental retardation, an outgoing personality and bone dysplasia.Case presentationWe report the first case of a five-year-old Colombian boy of mixed race ancestry (mestizo), with clinical features of microcephaly, prominent and narrow nose, arched palate, amelogenesis imperfecta, short stature, tall and narrow pelvis, disproportionate shortening of fore-arms and legs, and mild coxa vara. Analysis of the PCNT gene by sequencing showed the presence of a nucleotide change in exon 10, c. 1468C>T, evidencing a new mutation not reported in the literature for microcephalic osteodysplastic primordial dwarfism.ConclusionThe new mutation identified in this case could be associated with the severity of the phenotypic expression of the disease, resulting in the extreme short stature of the patient. Further studies are required to reach an explanation that can justify such findings, and it is vital to emphasize the importance of detection and follow-up by the epidemiological surveillance groups in birth defects and rare diseases.

Genetic cluster of fragile X syndrome in a Colombian district

Background:Fragile X syndrome (FXS) is the most common cause of inherited intellectual disabilities and autism. The reported prevalence of the full mutation (FM) gene FMR1 in the general population is 0.2–0.4 per 1000 males and 0.125–0.4 per 1000 females.Population screening for FMR1 expanded alleles has been performed in newborns and in an adult population. However, it has never been carried out in an entire town.Ricaurte is a Colombian district with 1186 habitants, with a high prevalence of FXS, which was first described by cytogenetic techniques in 1999.Methods:Using a PCR-based approach, screening for FXS was performed on blood spot samples obtained from 926 (502 males and 424 females) inhabitants from Ricaurte, accounting for 78% of total population.Results:A high prevalence of carriers of the expanded allele was observed in all FXS mutation categories. Using the Bayesian methods the carrier frequency of FM was 48.2 (95% Credibility Region CR: 36.3–61.5) per 1000 males and 20.5 (95% CR:13.5–28.6) per 1000 females; the frequency of premutation carrier was 14.1 (95% RC: 8.0–21.7) per 1000 males (95% RC: 8.0–21.7 per 1000 males) and 35.9 (95% RC: 26.5–46.2) per 1000 for females (95% RC: 26.5–46.2 per 1000 females), and gray zone carrier was 13.4 (95% RC: 7.4–20.7) per 1000 males (95% RC: 7.4–20.7 per 1000 males) and 42.2 (95% RC: 32.2–53.8) per 1000 for females (95% RC: 32.2–53.8 per 1000 females). Differences in carrier frequencies were observed for premutation and FM alleles between natives and non-natives.Conclusions:This study shows that in Ricaurte the carrier frequencies of FMR1 expanded alleles (premutations and FMs) are higher than those reported in the literature, suggesting that Ricaurte constitutes a genetic cluster of FXS.

Inequidades en el diagnóstico de anomalías congénitas mayores en recién nacidos en Cali, Colombia

SUMMARY Background: Major Congenital Anomalies (MCA) are present in 2-3% of live births. Most of these are diagnosable by prenatal ultrasound (PNUS). Developing countries have inequities in access to this screening test. Objectives: To determine existing inequities access to PNUS in mothers of newborns (NB) with MCA hospitalized in two neonatal intensive care units (NICU) and to identify inequities in the diagnosis of MCA among mothers to whom it was made at least one PNUS. Methods: Cross-sectional study in NB with MCA diagnosable by PNUS hospitalized in two NICUs of Cali, Colombia, between 2005 and 2009. The index of agreement (kappa) between prenatal diagnosis and definitive MCA was calculated. It was

Eight year follow-up of an epidemic of sirenomelia in Cali, Colombia.

Eight Year Follow-Up of an Epidemic of Sirenomelia in Cali, Colombia Wilmar Saldarriaga, Carolina Isaza, and Eduardo E. Castilla* Grupo de Malformaciones Congénitas Perinatales y Dismorfologı́a (MACOS), Departamento de Morfologı́a, Ginecologı́a y Obstetricia, Facultad de Ciencias de la Salud, Universidad del Valle, Cali, Valle, Colombia Instituto Nacional de Genética Médica Populacional (INAGEMP), Porto Alegre, Brazil, at ECLAMC (Latin American Collaborative Study of Congenital Malformations) in CEMIC (Center for Medical Education and Clinical Research), Buenos Aires, Argentina

Use of 3D Multislide CT in the Study of a Fetus with Cyclopia

La ciclopia es una malformacion congenita rara e incompatible con la vida, caracterizada por la presencia de un solo ojo en posicion central, secundaria a holoprosencefalia alobar. La ciclopia es de etiologia heterogenea, con una prevalencia de 1,05 en 100000 nacimientos. Presentamos un caso de ciclopia con sinoftalmia en un feto de 21 semanas en donde se utilizo tomografia computarizada multicorte 3D como estudio complementario.

Síndrome de Seckel, dos casos en una familia colombiana

El sindrome de Seckel es una enfermedad genetica de herencia autosomica recesiva de baja ocurrencia, caracterizado por la asociacion de talla baja, retardo mental y facies especial, se han reportado cerca de 10 familias con dos o mas miembros afectados. Nosotros reportamos dos hermanas hijas de padres no consanguineas, la madre presenta labio fisurado bilateral. Se describen las caracteristicas mas importantes del sindrome y se hace una revision de la literatura.