Polymorphisms in chromosome region 12q13 and their influence on age at onset of type 1 diabetes.

AIMS/HYPOTHESIS: A complex region covering numerous genes in 12q13 was first associated with type 1 diabetes in the Wellcome Trust Case-Control Consortium (WTCCC) study. Two studies performed in a white population have tested the association of polymorphisms within this region with age at onset of the disease, with seemingly contradictory results. We aimed at replicating three of the strongest signals in a group of patients with early and late disease onset. METHODS: Polymorphisms rs773107, rs2292239 and rs10876864 were genotyped in 444 type 1 diabetic Spanish participants (age at onset 0-65 years) and 861 controls. The influence of single nucleotide polymorphisms (SNPs) on age at onset was tested through stratified and continuous analyses. RESULTS: rs773107 and rs2292239 were significantly associated with the disease, while rs10876864 showed a trend towards statistical significance in the whole population analyses. Comparison of early-onset patients to controls was significant for the three polymorphisms (allelic p < 0.006). Late-onset patients and controls did not reveal statistical differences. Analysis of age at onset in both rs773107 and rs2292239 showed differences between genotypes (p ≤ 0.002), alleles (p ≤ 0.013) and homozygotes for the risk genotype (p ≤ 4 × 10(-4)). Polymorphism rs10876864 showed trends towards statistical significance in the allelic frequencies (p = 0.051) and homozygotes for the risk genotype (p = 0.056). Subjects with risk genotypes had a disease onset between 2 and 5 years earlier than carriers of protective alleles. CONCLUSIONS/INTERPRETATION: We replicate two of the previously studied associations in a Spanish population and find new evidence of the influence of the 12q13 region on age at onset of type 1 diabetes.

Benefits of exercise training in Spanish prison inmates.

Prison populations are growing in Western countries. Imprisoned people usually have a poor health status and an increased risk to suffer chronic debilitating conditions as coinfection with the HIV and hepatitis C virus (HCV) and/or opioid dependency. We studied the effects of a 4-month concurrent cardiorespiratory and resistance training program on the cardiorespiratory fitness, lower and upper body dynamic strength endurance (6-RM test for bench press and knee-extensor exercise, respectively), muscle mass and quality of life (QOL) of adult prison inmates who are HIV/HVC co-infected and enrolled in a methadone maintenance program (n = 9; mean [SD] age: 37 [3] yrs). We also evaluated a control group (n = 10; 37 [2] yrs). A significant combined effect of group and time was found for peak completed workload (W) (p < 0.01), peak heart rate (HR (peak)) (p < 0.05) and rate of HR decrease at 1-min postexercise compared to HR (peak) (p < 0.05), respectively, in a gradual cycle ergometer test. A significant combined effect of group and time was also found for both bench press and knee-extensor 6-RM tests, respectively (p < 0.05). Supervised exercise training can improve the overall physical fitness of incarcerated people. Our results suggest that this type of intervention could be applied in prisons of Western societies.

[Children with limb reductions in a population of 25,193 malformed newborns: the recognized causes. ECEMC. The Spanish Collaborative Study of Congenital Malformations]. / Niños con reducción de extremidades en una población de 25.193 recién nacidos malformados: causas reconocidas. ECEMC. Estudio Colaborativo Español de Malformaciones Congénitas.

OBJECTIVE: The purposes of this study were to analyze the causes of limb reduction deficiencies based on a clinical-epidemiological approach and to study the causes by clinical presentation. PATIENTS AND METHODS: We have used the data from the Spanish Collaborative Study of Congenital Malformations (ECEMC) during the period from 1976 to 1996, which corresponded to more than 1,300,000 births. Among these, we identified 851 liver-born and 40 stillborn infants with limb reduction defects. RESULTS: We could identify the cause in 177 (19.87%) of the 891 cases with limb reduction defects. In the analysis by clinical presentation, in 52.19% of the cases the limb deficiencies were the only defect present in the children (isolated), 30.75% presented multiple congenital anomaly patterns, and 17.06% were syndromes. The most frequent etiology was the genetic one. CONCLUSIONS: First, most of infants with limb deficiencies have unknown cause and these defects are most frequently isolated malformations. On the other hand, the results of this analysis permitted the following considerations in relation to the guidance for the diagnosis of infants with limb reduction defects. If the child presents with multiple congenital anomalies (multiply malformed infant) a chromosomal analysis should be performed and it should be determined if the infant was prenatally exposed to a teratogenic agent. If these two aspects are normal, we should clinically analyze if the infant could have a known syndrome. In addition, since in our data 10.32% of isolated cases were due to autosomal dominant genes, a detailed clinical analysis of close relatives should be done to determine if some of them present mild limb deficiencies in order to provide an adequate information to the family.

Amelia: analysis of its epidemiological and clinical characteristics.

Eighteen cases of amelia in the Spanish Collaborative Study of Congenital Malformations (ECEMC) were analyzed epidemiologically. Prevalence at birth was 0.15 per 10,000 newborn infants, which is not different from that reported by other authors. Affected females outnumbered males. When compared with the control group, a lower birth weight, shorter gestation, lower placental weight, greater frequency of single umbilical artery, noncephalic presentation at birth, and more frequent maternal vaginal bleeding were observed in amelia cases. There were no significant variations of parental age. None of these patients was exposed to known teratogens, apart from 1 born to a diabetic mother; 3 patients had a genetic condition. Comparison of these variables with other studies is difficult because there is only one study that specifically analyzed amelia. Our data together with previous observations suggest that the genetic basis of amelia might be more important than has been considered previously.

Primary midline developmental field. II. Clinical/epidemiological analysis of alteration of laterality (normal body symmetry and asymmetry).

Lubinsky [Am J Med Genet 3:23-28, 1987] has suggested that the properties of the midline involve early determinative informational processes and are related to the midline's position and definition of the body's plane of symmetry. Opitz [Am J Med Genet 21:175-176, 1985, BD: OAS XXIX(1):3-37 1993] has pointed out that the laterality sequences represent a midline developmental field complex. Thus, bilateral left-sidedness (with asplenia) and bilateral right-sidedness (with asplenia) have been considered laterality sequences or syndromes if cause is known. Using the malformed infants registered by the Spanish Collaborative Study of Congenital Malformations (ECEMC), we performed a clinical/epidemiological analysis of the relationship between midline defects and alteration of normal body asymmetry and symmetry. The results support the assumption that both conditions could be consequence of disturbances in the midline primary developmental field.

DK-phocomelia syndrome in a child with a long follow-up.

We report on an 8-year-old boy with a pattern of multiple congenital anomalies that strongly suggest DK-phocomelia syndrome. Birth findings included bilateral upper limb amelia, occipital encephalocele, agenesis of the corpus callosum, right auricular tag, scoliosis, small penis, and cryptorchidism. Dental malocclusion was observed in the follow-up. This is the first case with on 8-year follow-up report of DK-phocomelia syndrome.

Severe spondylocostal dysostosis associated with other congenital anomalies: a clinical/epidemiologic analysis and description of ten cases from the Spanish registry.

We describe 10 cases born to nondiabetic mothers who presented with severe spondylocostal dysostosis (SCD) associated with other anomalies, identified among 20,526 malformed liveborn infants from the Spanish Collaborative Study of Congenital Malformations (ECEMC). We analyze the associated malformations in the 10 cases with severe SCD, as well as in all cases with less severe SCD among children with MCA patterns of unknown cause. Cases with SCD were preferentially associated with caudal dysgenesis, diaphragmatic hernia, and central nervous system anomalies.

Tracheoesophageal fistula, gastrointestinal abnormalities, hypospadias, and prenatal growth deficiency.

We studied 2 sibs, born to consanguineous parents, who presented with an MCA pattern which includes low birthweight, tracheoesophageal fistula, duodenal atresia, extrahepatic biliary atresia, hypoplastic pancreas, and hypospadias. This constellation of congenital anomalies appears to be a previously unreported autosomal recessive syndrome. A computerized search of the data files of the Spanish Collaborative Study of Congenital Malformations (ECEMC) identified 3 other unrelated infants with intestinal atresias, hypospadias, and low birth weight. These cases may represent a milder expression of the same syndrome.

Cerebral abnormalities in congenital myotonic dystrophy.

The brain structure of 14 infants born with congenital myotonic dystrophy at 2 hospitals was evaluated by cranial ultrasonography, and the findings were correlated with clinical and neuropathologic data. Ventricular dilation was diagnosed in 11 infants (78%). Seven infants died during the neonatal period; all had ventricular dilation which remained essentially static. In the ultrasound scans of the 5 infants with ventricular dilation. Of the 7 survivors, 4 had ventricular dilation born at 1 hospital, 4 had widening of the interhemispheric fissure. Macrocephaly, a previously unrecognized finding in congenital myotonic dystrophy, was present in 10 infants (71%), 8 of whom presented with ventricular dilation. None had clinical evidence of increased intracranial pressure. There was no ventricular obstruction in the 4 brains examined pathologically. Histologic examination revealed minor expression of neuronal migrational disturbances in each patient. Macrocephaly together with the ultrasonographic and neuropathologic findings in our patients suggest that these abnormalities may originate in an external hydrocephalus.

[Neonatal findings in children of drug-addicted mothers]. / Hallazgos neonatales en hijos de drogadictas.

A group of 13 babies born to heroin-addict mothers has been studied in our Department during the last three years. Authors have recorded clinical features like neonatal abstinence syndrome, malformations, intrauterine growth, maternal age, gestational duration and delivery. They discuss different types of malformations and withdrawal symptoms, and make a comparative study with normal newborns of our hospital.

[Pancreatic resection in the treatment of infantile hypoglycaemia]. / La pancreatectomía en el tratamiento de la hipoglucemia.

Authors report four patients with hyperinsulinemic unremitting hypoglycaemia due to pancreatic nesidioblastosis. Onset was neonatal in three of them and at the end of the first year in the remaining one. After variable periods of only partially successful medical therapy, the four patients were operated and subtotal pancreatectomy was carried out. This alone was sufficient in one case, and in another one diazoxide made control possible. The other two children had a total pancreatectomy, and one of them has needed insulin ever since. Hypoglycaemia is under control in all children and only one has mental impairment. Diagnostic work-up and surgical techniques are described, and the need for a prompt operation when medical control is incomplete is stressed. Although apparently a blind and major undertaking, surgery is still the only way of preserving neuronal function in some selected cases.

[Urology aspects of adrenogenital syndrome]. / Aspectos urológicos del síndrome adrenogenital.

During the past five years, 10 patients (seven girls and three boys) with virilizing adrenal hyperplasia have been treated in our institution. A thorough urological work-up was preformed in all. We found among the girls one ureteral duplication, three lower urinary obstruction (two of them in girls with high urethro-vaginal confluence) and four bilateral vesico-ureteral refluxes. Two girls required a Hendren operation, and the remaining had a convention cut-back. Obstruction disappeared in all cases, but reflux persists in one of the patients. The plastic results were constantly good. A detailed urological investigation is strongly advised for patients with adrenogenital syndrome.

[Rectal agenesis with absent bladder in a female newborn (author's transl)]. / Agénésie rectale avec absence de vessie chez une fille.

This paper reports a very unusual variety of female ano-rectal agenesis without fistula associated with severe urogenital malformations. The patient died of renal failure and, at autopsy, both ureters draining dysplastic ectopic kidneys and two vaginas, either with its corresponding uterus and annexa were found opening to s single perineal orifice through a very narrow conduit. Bladder and urachus were absent and a single left umbilical artery was found. This infant had also thoracic vertebral anomalies.

[Neonatal listeriosis. Presentation of nine cases (author's transl)]. / Listeriosis neonatal. A propósito de nueve observaciones

Nine cases of neonatal listeriosis observed in 1973 and 1974 are presented. Diagnosis was established during life in eight cases by positivity of bacteriological cultures. Given the high incidence of listeria sepsis and the important mortality, it is necessary to establish an early diagnosis, an immediate antibiotic therapy and provide intensive care in an special unit.