Wilmar Saldarriaga

Fragile X syndrome.

The fragile X syndrome is the most common inherited form of mental retardation known. Its phenotype includes large or prominent ears, macroorchidism, and characteristic behavioral problems. It has attracted the interest of cytogeneticists and molecular biologists because of its characteristic fragile site on the X chromosome. It has puzzled geneticists because of its unusual inheritance pattern involving nonpenetrant males. This syndrome has also spearheaded an appreciation of cytogenetic abnormalities in the etiology of all degrees of developmental delay.

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.

A factorial randomized controlled trial to evaluate the effect of micronutrients supplementation and regular aerobic exercise on maternal endothelium-dependent vasodilatation and oxidative stress of the newborn

BackgroundMany studies have suggested a relationship between metabolic abnormalities and impaired fetal growth with the development of non-transmissible chronic diseases in the adulthood. Moreover, it has been proposed that maternal factors such as endothelial function and oxidative stress are key mechanisms of both fetal metabolic alterations and subsequent development of non-transmissible chronic diseases. The objective of this project is to evaluate the effect of micronutrient supplementation and regular aerobic exercise on endothelium-dependent vasodilation maternal and stress oxidative of the newborn.Methods and design320 pregnant women attending to usual prenatal care in Cali, Colombia will be included in a factorial randomized controlled trial. Women will be assigned to the following intervention groups: 1. Control group: usual prenatal care (PC) and placebo (maltodextrine). 2. Exercise group: PC, placebo and aerobic physical exercise. 3. Micronutrients group: PC and a micronutrients capsule consisting of zinc (30 mg), selenium (70 μg), vitamin A (400 μg), alphatocopherol (30 mg), vitamin C (200 mg), and niacin (100 mg). 4. Combined interventions Group: PC, supplementation of micronutrients, and aerobic physical exercise. Anthropometric measures will be taken at the start and at the end of the interventions.DiscussionSince in previous studies has been showed that the maternal endothelial function and oxidative stress are related to oxidative stress of the newborn, this study proposes that complementation with micronutrients during pregnancy and/or regular physical exercise can be an early and innovative alternative to strengthen the prevention of chronic diseases in the population.Trial registrationNCT00872365.

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.

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.

Myasis in uterine prolapse, successful treatment.

We describe the case of an elderly female with total genital prolapse and superinfected uterine myasis. The successful treatment included mechanical extraction of the larvae, antibiotics, and ivermectin (this last one reported for the first time); along with the surgical correction of the prolapse.

Alcohol use dependence in fragile X syndrome

Alcohol use disorders (AUDs) have been reported in a limited number of individuals with cognitive impairment but rarely in those with fragile X syndrome (FXS). However, in Colombia, culturally, alcohol consumption is very common. Here, we report eight cases of patients with FXS who have frequent alcohol consumption in Ricaurte, Colombia. Some of these patients have also used tobacco and illegal substances, including cocaine, which use has not been previously reported in those with FXS. Alcohol and substance use dependence is associated with exacerbation of their behavioral problems, such as increased impulsivity and aggression, as well as of medical problems such as an increased frequency of seizures.

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.

Down Syndrome and Fragile X Syndrome in a Colombian Woman: Case Report.

BACKGROUND Down syndrome (DS) and Fragile X syndrome (FXS) are the major genetic causes of intellectual disabilities. Here, we present a case of a 32-year-old woman with the diagnosis of both FXS and DS. She is the daughter of a 47-year-old pre-mutation woman who also has three sons with FXS. METHODS Cytogenetic testing detected the presence of a complete trisomy 21. A combination of PCR and Southern blot analysis was utilized to document the presence of the FMR1 full mutation. RESULTS The patient has physical characteristics and behavioural disturbances typical of both FXS and DS, which were confirmed by molecular testing. Her treatment plan included a trial of sertraline because of the severity of her shyness and lack of language. She had an excellent response to sertraline with improvement in shyness and social interactions, particularly with family members. CONCLUSIONS In this study, we report the case of a woman with both FXS and DS, which is the fifth case of FXS and DS in the worlds literature. The patient is from Ricaurte, a small town in Colombia, South America, where there is the worlds highest prevalence for FXS.

Fragile X syndrome and fragile X-associated disorders

Fragile X syndrome (FXS) is caused by a full mutation on the FMR1 gene and a subsequent lack of FMRP, the protein product of FMR1. FMRP plays a key role in regulating the translation of many proteins involved in maintaining neuronal synaptic connections; its deficiency may result in a range of intellectual disabilities, social deficits, psychiatric problems, and dysmorphic physical features. A range of clinical involvement is also associated with the FMR1 premutation, including fragile X-associated tremor ataxia syndrome, fragile X-associated primary ovarian insufficiency, psychiatric problems, hypertension, migraines, and autoimmune problems. Over the past few years, there have been a number of advances in our knowledge of FXS and fragile X-associated disorders, and each of these advances offers significant clinical implications. Among these developments are a better understanding of the clinical impact of the phenomenon known as mosaicism, the revelation that various types of mutations can cause FXS, and improvements in treatment for FXS.