Recomendaciones de buenas prácticas para el diagnóstico genético de abortos espontáneos e interrupciones voluntarias del embarazo por presentar defectos congénitos / Good practice recommendations in the molecular diagnosis of miscarriage and abortion due to multiple congenital malformations

Objetivos: La aparición de defectos congénitos produce una gran ansiedad en la familia y una enorme demanda asistencial. El objetivo principal radica en la redacción de las recomendaciones de buenas prácticas que sirvan de guía a los profesionales sanitarios para el diagnóstico clínico-genético de defectos congénitos. Metodología: El protocolo que proponemos contempla un modelo de actuación óptimo que incluye, la recogida de la información clínica inicial, la obtención de las muestras biológicas y los protocolos de actuación. Resultado: Se ha elaborado un modelo de historia clínica que ayude a la recogida de la información clínica pertinente. En la obtención de las muestras biológicas se aconseja la obtención de muestras fetales (de las 3 capas embrionarias) y muestras de los progenitores que serán procesarán teniendo en cuenta el algoritmo de actuación propuesto para el correcto diagnóstico genético del defecto congénito correspondiente. Conclusión: Esta guía recoge por primera vez, las recomendaciones de buenas prácticas para el diagnóstico genético de abortos con defectos congénitos

Aims: Congenital anomalies can cause anxiety within a family and high healthcare demand. The aim of this study was to write good practice recommendations to guide health professionals in the clinical-genetic diagnosis of congenital defects. Methods: The proposed protocol focuses on an optimal case scenario that includes collection of initial clinical data, biological sampling, and diagnostic algorithms. Results: A model of the optimal clinical history form was created to facilitate the collection of initial clinical data. For sampling, it is recommended to obtain at least one fetal sample (of the three embryonic germ layers). Moreover, samples from both parents should be taken to exclude mosaicism, following the diagnostic algorithm proposed for the correct genetic diagnosis of the corresponding congenital defect. Conclusion: This document is the first to gather good practice recommendations for the pre- and post-natal genetic diagnosis of miscarriages and abortions due to congenital defects

Novel (60%) and recurrent (40%) androgen receptor gene mutations in a series of 59 patients with a 46,XY disorder of sex development.

BACKGROUND: Androgen receptor (AR) gene mutations are the most frequent cause of 46,XY disorders of sex development (DSD) and are associated with a variety of phenotypes, ranging from phenotypic women [complete androgen insensitivity syndrome (CAIS)] to milder degrees of undervirilization (partial form or PAIS) or men with only infertility (mild form or MAIS). OBJECTIVE: The aim of the study was to characterize the contribution of the AR gene to the molecular cause of 46,XY DSD in a series of Spanish patients. SETTING: We studied a series of 133 index patients with 46,XY DSD in whom gonads were differentiated as testes, with phenotypes including varying degrees of undervirilization, and in whom the AR gene was the first candidate for a molecular analysis. METHODS: The AR gene was sequenced (exons 1 to 8 with intronic flanking regions) in all patients and in family members of 61% of AR-mutated gene patients. RESULTS: AR gene mutations were found in 59 individuals (44.4% of index patients), of whom 46 (78%) were CAIS and 13 (22%) PAIS. Fifty-seven different mutations were found: 21.0% located in exon 1, 15.8% in exons 2 and 3, 57.9% in exons 4-8, and 5.3% intronic. Twenty-three mutations (40.4%) had been previously described and 34 (59.6%) were novel. CONCLUSIONS: AR gene mutation is the most frequent cause of 46,XY DSD, with a clearly higher frequency in the complete phenotype. Mutations spread along the whole coding sequence, including exon 1. This series shows that 60% of mutations detected during the period 2002-2009 were novel.

Coloboma palpebral bilateral: una malformación ocular poco frecuente / Bilateral palpebral coloboma: an infrequent ocular malformation

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X-linked hydrocephalus: another two families with an L1 mutation.

X-linked hydrocephalus is a variable condition caused by mutations in the gene encoding for L1CAM. This gene is located at Xq28. Clinically the spectrum ranges from males with lethal congenital hydrocephalus to mild/moderate mental retardation and spastic paraplegia. Few carrier females show minimal signs of the syndrome. Although most cases are familial, de novo situations have been reported. We report two new families with the syndrome and a L1 mutation. Family 1 has two patients and family 2 a single patient. Clinical diagnosis in all three affected boys was beyond doubt. Prenatal testing through chorionic villus biopsy is possible only with a demonstrated L1 mutation. In lethal sporadic cases neuropathology is very important in order to evaluate for features of the syndrome. We stress the importance of further clinical reports including data on neuropathology and DNA analysis in order to further understand the mechanisms involved in this disorder.

Síndrome PFAPA: un nuevo caso / PFAPA syndrome: a new case

Se describe un caso de síndrome PFAPA en un niño de 4 años. Este síndrome consiste en episodios de fiebre periódica, estomatitis aftosa, faringitis y linfadenopatía cervical. Aunque es un proceso benigno, se acompaña de gran morbilidad y alto componente de ansiedad familiar, debido a que los episodios recurren periódicamente (AU)

A case of PFAPA syndrome in a 4-year-old boy is presented. The syndrome consists of periodic fever, aphthous stomatitis, pharyngitis and adenopathy. The disorder is benign, but is associated with a high morbidity rate. Ultimately, there is a progressive decrease in the incidence of periodic fever (AU)

Localization of non-specific X-linked mental retardation gene (MRX73) to Xp22.2.

Clinical and molecular studies are reported on a family (MRX73) of five males with non-specific X-linked mental retardation (XLMR). A total of 33 microsatellite and RFLP markers was typed. The gene for this XLMR condition was been linked to DXS1195, with a lod score of 2.36 at theta = 0. The haplotype and multipoint linkage analyses suggest localization of the MRX73 locus to an interval of 2 cM defined by markers DXS8019 and DXS365, in Xp22.2. This interval contains the gene of Coffin-Lowry syndrome (RSK2), where a missense mutation has been associated with a form of non-specific mental retardation. Therefore, a search for RSK2 mutations was performed in the MRX73 family, but no causal mutation was found. We hypothesize that another unidentified XLMR gene is located near RSK2.

[Spontaneous resolution of a congenital depressed skull fracture]. / Fractura hundimiento craneal congénita con resolución espontánea.

Congenital depressed skull fracture is rare and in most cases its etiology remains unclear. We present a female newborn infant with a congenital depressed skull fracture and no evidence of antepartum or intrapartum traumatism. The baby had normal neurological status and the depressed fracture healed spontaneously in a few weeks. Based on our experience of this case and a literature review, we conclude that congenital depressed skull fractures should be managed conservatively if the skull depression is less than 2cm, there is no previous trauma, no local edema or hematoma, and if the neonate shows normal neurological status.

Fractura-hundimiento craneal congénita con resolución espontánea / Spontaneous resolution of a congenital depressed skull fracture

Las fracturas craneales congénitas son un proceso poco frecuente cuya etiología queda en la mayoría de casos sin aclarar. Se presenta el caso de una recién nacida con fractura hundimiento craneal congénita, sin antecedente de traumatismo anteparto o intraparto, que evolucionó sin presentar ninguna sintomatología que, manteniendo una actitud expectante, presentó resolución espontánea de la fractura dentro de las primeras semanas de vida. Basándose en la experiencia de este caso y tras revisar la bibliografía sobre el tema la conclusión es que si no existe traumatismo previo, el recién nacido permanece neurológicamente asintomático, no hay signos locales de edema o hematoma y el hundimiento es menor de 2 cm, lo más recomendable consiste en una actitud expectante sin proceder a la reducción quirúrgica inmediata, ya que en estos casos la resolución espontánea es el resultado más probable (AU)

Single aberrant umbilical artery in a fetus with severe caudal defects: sirenomelia or caudal dysgenesis.

We describe a 1,000-g twin fetus with absent kidneys and ureters, anal atresia and minimal evidence of external genitalia, and hypoplastic lower limbs with absent feet. A postmortem arteriogram showed a large single umbilical artery in direct continuation with the abdominal aorta, a unique anomaly almost always related to sirenomelia. We discuss the possible diagnosis of this case as sirenomelia or caudal dysgenesis, and the controversy as to whether they are two related or separate entities.

Non-immunological hydrops fetalis and intrapericardial teratoma: case report and review.

A large intrapericardial teratoma was found at necropsy in a 38-week stillborn fetus, in which prenatal diagnosis of hydrops fetalis and an echogenic cardiac mass had been made. Clinical and pathological data are reported. In utero intrapericardial teratomata lead to different outcomes depending on whether fetal hydrops is associated. When generalized fetal hydrops is not present, the outcome is good, even in cases with large pericardial effusions. When generalized fetal hydrops occurs, it often results in a poor outcome. In our literature review, we have found eight perinatal deaths in nine similar cases reported.

[The effect of moderate intake of alcohol during pregnancy on the weight of the newborn]. / Efecto del consumo moderado de alcohol durante el embarazo sobre el peso del recién nacido.

BACKGROUND: There is currently no doubt concerning the detrimental effects of the intake of high doses of alcohol during pregnancy. Nonetheless, there has been some controversy regarding the effects of intake of low or moderate quantities of alcohol. The aim of the present study, carried out within the framework of a more extensive European study (EUROMAC), was to specifically analyze the relation between moderate intake of alcohol in pregnant women and the weight of the newborns. METHODS: A prospective cohort study including 1,005 women who attended prenatal consultation in the Hospital La Fe of Valencia between 12 and 18 weeks of pregnancy during 1989 was performed. All the subjects were asked on alcohol intake during the week prior to the interview with data on other sociodemographic and biologic variables being collected. Variance analysis was carried out to evaluate the association of the weight of the newborn with alcohol intake as well as with each of the control variables. Multiple lineal regression analysis was performed by the minimum squares method to evaluate possible effects of confusion and interaction. RESULTS: Following adjustment for parity, weight of the mother prior to pregnancy, sex of the newborn, age at pregnancy and tobacco consumption, only a slight reduction in the weight of the newborns was observed in the category of intake greater than 90 g/week, however this difference was not statistically significant. CONCLUSIONS: The low or moderate intake of alcohol during the first months of pregnancy has no detectable effect on fetal growth.

Urethral obstruction sequence and lower limb deficiency: evidence for the vascular disruption hypothesis.

We reviewed five unreported examples and 23 previously reported cases of urethral obstruction sequence with associated lower limb deficiency. There was no evidence of amniotic bands or exposure to vasoactive drugs during pregnancy in any case. In three infants a gangrenous lesion at the distal part of the affected leg was found; in another three infants, necrotic tissue was noted in the stump of the affected leg. This type of lesion can be explained only on a vascular ischemic basis. In five cases, signs of compression of the external iliac artery by the grossly distended bladder, by grossly distended ureters, or both were found. A vascular disruption in the territory of the external iliac artery caused by compression by the distended urinary tract is the proposed mechanism for the associated limb deficiency.