5α-Reductase type 2 deficiency in families from an isolated Andean population in Venezuela.

5α-Reductase type 2 deficiency causes a 46,XY disorder of sex development (DSD) characterized by ambiguous external genitalia, rudimentary prostate, and normal internal genitalia. The disease prevalence worldwide is low, but in a small and isolated village of the Venezuelan Andes, a higher incidence has been found. DNA analysis of the SRD5A2 gene was performed in three inbred affected individuals clinically diagnosed with DSD. The entire coding regions, the p.L89V polymorphism (rs523349) and five intragenic SNPs (rs2300702, rs2268797, rs2268796, rs4952220, rs12470196) used to construct haplotypes were analyzed by Sanger sequencing. To assess the probable ethnic origin of the mutation in this geographic isolate, a population structure analysis was performed. Homozygosis for the p.N193S mutation was found in all patients, with a mutation carrier frequency of 1:80 chromosomes (0.0125) in the geographic focus, suggesting a founder phenomenon. The results of the population structure analysis suggested a mutation origin closer to the Spanish populations, according to the clusters grouping. The genotype-phenotype correlation in the patients was not absolute, being hypospadias and cryptorchidism the main traits that differentiate affected individuals.

[Psychological resistance to use insulin in type 2 diabetes mellitus patients from Venezuela]. / Resistencia psicológica al uso de insulina en pacientes con diabetes mellitus tipo 2 en una población venezolana.

The psychological resistance to use insulin (PIR) is a condition where the patient with type 2 diabetes mellitus (T2DM) refuses to use insulin. Our objective was to determine the frequency of PIR in a Venezuelan population and their beliefs regarding insulin and current medication. In several states of Venezuela, from January to March 2013, 254 patients with T2DM, over 18 years old and naive to insulin treatment were interviewed. We applied an interview to evaluate the disposition of the patients to use insulin if their doctor prescribes it and to determine their beliefs about insulin and their current medication. The patients were categorized in: not willing (PIR group), ambivalent and willing to use insulin. The beliefs about insulin and their current medication were grouped into positive or negative. The mean age was 56.2 years, with 7.1 years of duration of the T2DM; 58.6% were females. One third (32.7%) had PIR, 20.9% were ambivalent and 46.4% were willing to use insulin. PIR patients showed lower frequency of positive beliefs and more frequency of negative beliefs to insulin and to their current treatment (p < 0.0001). Negative beliefs to insulin increased 14 times the risk of PIR, and people without university studies had a four times increase in the risk of PIR compared to the willing group. In conclusion, a high frequency of PIR in patients with T2DM (32.7%) was found in Venezuela; they showed low frequency of positive beliefs and high frequency of negative beliefs about insulin use. It is necessary to improve T2DM patient education on this issue.

A Severe Case of Spondylometaphyseal Dysplasia Algerian Type with Two Mutations in COL2A1.

Spondylometaphyseal dysplasia Algerian type (MIM no.: 184253) is an uncommon autosomal dominant skeletal dysplasia caused by heterozygous mutations in the COL2A1 gene (MIM no.: 120140). In this case based review, we reported a 5-year-old boy with short stature, severe dorsolumbar scoliosis, lumbar hyperlordosis, short trunk, and severe genu valgum . Radiological examination showed platyspondyly, irregular metaphyseal radiolucencies intermingled with radiodensities, and corner fractures. The patient has a c.3275G > A; p.Gly1092Asp mutation in exon 47 of the COL2A1 gene and a variant of unknown significance in c.1366-13C > A in intron 21. This latter sequence variant could partially or completely disrupt the natural splice acceptor site of intron 21/exon 22 in the COL2A1 gene leading to a potential modification of the phenotypic severity.

Next generation sequencing panel target genes: possible diagnostic tool for ectodermal dysplasia related diseases.

BACKGROUND: Ectodermal dysplasias (EDs) are a large and complex group of disorders affecting the ectoderm-derived organs; the clinical and genetic heterogeneity of these conditions renders an accurate diagnosis more challenging. The aim of this study is to demonstrate the clinical utility of a targeted resequencing panel through enhancing the molecular and clinical diagnosis of EDs. Given the recent developments in gene and protein-based therapies for X-linked hypohidrotic ectodermal dysplasia, there is a re-emerging interest in identifying the genetic basis of EDs and the respective phenotypic presentations, in an aim to facilitate potential treatments for affected families. METHODS: We assessed seventeen individuals, from three unrelated families, who presented with diverse phenotypes suggestive of ED. An extensive multidisciplinary clinical evaluation was performed followed by a targeted exome resequencing panel (including genes that are known to cause EDs). MiSeqTM data software was used, variants with Qscore >30 were accepted. RESULTS: Three different previously reported hemizygous EDA mutations were found in the families. However, a complete genotype-phenotype correlation could not be established, neither in our patients nor in the previously reported patients. CONCLUSIONS: Targeted exome resequencing can provide a rapid and accurate diagnosis of EDs, while further contributing to the existing ED genetic data. Moreover, the identification of the disease-causing mutation in an affected family is crucial for proper genetic counseling and the establishment of a genotype-phenotype correlation which will subsequently provide the affected individuals with a more suitable treatment plan.

An updated examination of the perception of barriers for pharmacogenomics implementation and the usefulness of drug/gene pairs in Latin America and the Caribbean.

Pharmacogenomics (PGx) is considered an emergent field in developing countries. Research on PGx in the Latin American and the Caribbean (LAC) region remains scarce, with limited information in some populations. Thus, extrapolations are complicated, especially in mixed populations. In this paper, we reviewed and analyzed pharmacogenomic knowledge among the LAC scientific and clinical community and examined barriers to clinical application. We performed a search for publications and clinical trials in the field worldwide and evaluated the contribution of LAC. Next, we conducted a regional structured survey that evaluated a list of 14 potential barriers to the clinical implementation of biomarkers based on their importance. In addition, a paired list of 54 genes/drugs was analyzed to determine an association between biomarkers and response to genomic medicine. This survey was compared to a previous survey performed in 2014 to assess progress in the region. The search results indicated that Latin American and Caribbean countries have contributed 3.44% of the total publications and 2.45% of the PGx-related clinical trials worldwide thus far. A total of 106 professionals from 17 countries answered the survey. Six major groups of barriers were identified. Despite the region's continuous efforts in the last decade, the primary barrier to PGx implementation in LAC remains the same, the "need for guidelines, processes, and protocols for the clinical application of pharmacogenetics/pharmacogenomics". Cost-effectiveness issues are considered critical factors in the region. Items related to the reluctance of clinicians are currently less relevant. Based on the survey results, the highest ranked (96%-99%) gene/drug pairs perceived as important were CYP2D6/tamoxifen, CYP3A5/tacrolimus, CYP2D6/opioids, DPYD/fluoropyrimidines, TMPT/thiopurines, CYP2D6/tricyclic antidepressants, CYP2C19/tricyclic antidepressants, NUDT15/thiopurines, CYP2B6/efavirenz, and CYP2C19/clopidogrel. In conclusion, although the global contribution of LAC countries remains low in the PGx field, a relevant improvement has been observed in the region. The perception of the usefulness of PGx tests in biomedical community has drastically changed, raising awareness among physicians, which suggests a promising future in the clinical applications of PGx in LAC.

[Clinical and molecular study of the Noonan syndrome]. / Estudio clínico y molecular del síndrome de Noonan.

Noonan syndrome is a relatively common autosomal dominant entity, clinically variable and genetically heterogeneous; characterized by postnatally reduced growth, distinctive facial dysmorphism, cardiac defects and variable cognitive deficits. The PTPN11 gene is located on the long arm of chromosome 12 and is primarily responsible for the clinically diagnosed cases of this entity. We report the case of a 18 month-old boy, evaluated in a multidisciplinary way, with clinic and molecular diagnosis of Noonan syndrome, with the missense mutation in PTPN11 gene, G503R (c.1507 G>A). Several clinical features and the genetic alterations associated with this mutation are discussed.

Clinical and genetic findings of two cases with Apert syndrome.

Background: Craniosynostosis is described as the premature fusion of cranial sutures that belongs to a group of alterations which produce an abnormal phenotype. Case report: Two unrelated female patients with clinical findings of Apert syndrome-characterized by acrocephaly, prominent frontal region, flat occiput, ocular proptosis, hypertelorism, down-slanted palpebral fissures, midfacial hypoplasia, high-arched or cleft palate, short neck, cardiac anomalies and symmetrical syndactyly of the hands and feet-are present. In both patients, a heterozygous missense mutation (c.755C>G, p.Ser252Trp) in the FGFR2 gene was identified. Conclusions: Two cases of Apert syndrome are described. It is important to recognize this uncommon entity through clinical findings, highlight interdisciplinary medical evaluation, and provide timely genetic counseling for the family.

Introducción: Las craneosinostosis se describen como la fusión prematura de las suturas craneales y resultan un grupo de alteraciones que producen un fenotipo anormal. Caso clínico: En este informe de casos se presentan dos pacientes de sexo femenino no emparentadas con hallazgos clínicos del síndrome de Apert, caracterizado por acrocefalia, región frontal prominente, occipucio plano, proptosis ocular, hipertelorismo, fisuras palpebrales hacia abajo, hipoplasia mediofacial, paladar alto o hendido, cuello corto, cardiopatía congénita y sindactilia simétrica en manos y pies. En ambas pacientes se identificó una mutación cambio de sentido en heterocigosis (c.755C>G, p.Ser252Trp) en el gen FGFR2. Conclusiones: Se presentan dos casos de síndrome de Apert. Es importante reconocer a través de los hallazgos clínicos esta entidad infrecuente, resaltar la evaluación médica interdisciplinaria y proporcionar un oportuno asesoramiento genético a la familia.

[Clinical, biochemical and molecular findings of propionic acidemia]. / Hallazgos clínicos, bioquímicos y moleculares de la acidemia propiónica: reporte de un caso.

Propionic acidemia is an infrequent disorder with an autosomal recessive inheritance pattern caused by the deficiency of the mitochondrial enzyme propionyl-CoA carboxylase that converts propionyl-CoA to D-methylmalonyl-CoA. We present the case of a male newborn who showed signs of respiratory distress, vomiting and tiredness during feeding. He presented metabolic acidosis, positive serum and urine ketone bodies, hyperammonemia, anemia, thrombocytopenia and hypoproteinemia. The biochemical study by gas chromatography coupled to mass spectrometry in a urine sample was suggestive of propionic acidemia. The molecular study in the PCCA gene found the mutations c.893A>G (p.K298R) in the father and c.937C> T (p.R313X) in the mother. There is a need to establish the diagnosis of this infrequent entity to implement the therapeutic measures available and provide the appropriate genetic counseling.

La acidemia propiónica es un trastorno infrecuente con patrón de herencia autosómico recesivo causado por la deficiencia de la enzima mitocondrial propionil-CoA carboxilasa, que convierte el propionil-CoA a D-metilmalonil-CoA. Se expone el caso de un recién nacido masculino con signos de dificultad respiratoria, vómitos y cansancio durante la alimentación. Presentó acidosis metabólica, cuerpos cetónicos en el suero y la orina positivos, hiperamonemia, anemia, trombocitopenia e hipoproteinemia. El estudio bioquímico por cromatografía de gases acoplada a espectrometría de masas en la muestra de orina fue sugestivo de acidemia propiónica. El estudio molecular en el gen PCCA encontró las mutaciones c.893A>G (p.K298R) en el padre y c.937C>T (p.R313X) en la madre. Existe la necesidad de establecer el diagnóstico de esta entidad infrecuente para implementar las medidas terapéuticas disponibles y aportar el oportuno asesoramiento genético.

A Venezuelan Case of Schmid-Type Metaphyseal Chondrodysplasia with a Novel Mutation in COL10A1.

Schmid-type metaphyseal chondrodysplasia (MIM 156500) is an uncommon autosomal dominant skeletal dysplasia caused by heterozygous mutations in the COL10A1 gene (MIM 120110) encoding the α1(X) chains of type X collagen. We report an 8-year-old girl with waddling gait, short stature, mild dorsal scoliosis, coxa vara, short lower limbs, bowing of the femurs, genu varum, and metaphyseal fraying and splaying, who is a carrier of a novel heterozygous 2-bp (c.1894_1895dupTA; p.Leu633Thrfs*45) duplication in exon 3 of the COL10A1 gene.

[Wolf-Hirschhorn syndrome. Description of five cases characterized by means of single nucleotide polymorphism microarrays]. / Síndrome de Wolf-Hirschhorn. Descripción de cinco casos caracterizados por microarrays de polimorfismos de nucleótido único.

Wolf-Hirschhorn syndrome is a polymalformative entity due to the microdeletion in the distal region of the short arm of chromosome 4 (4p16.3), which produces a series of clinical manifestations that can vary depending on the type and size of the genetic defect in this contiguous gene syndrome. Five patients are presented, three of them female, all with the primary clinical findings, characterized by "Greek warrior helmet appearance" facial feature, growth retardation and psychomotor development delay. In addition to the partial deletion in the distal region of the short arm of chromosome 4, two additional genetic alterations were found in two patients, through the use of single nucleotide polymorphism arrays. The clinical characteristics of Wolf-Hirschhorn syndrome are highlighted in order to guide the diagnosis, provide interdisciplinary medical care and, through its confirmation, provide adequate family genetic counseling.

El síndrome de Wolf-Hirschhorn es una entidad polimalformativa debida a la microdeleción en la región distal del brazo corto del cromosoma 4 (4p16.3), el cual produce una serie de manifestaciones clínicas, que pueden variar dependiendo del tipo y tamaño del defecto genético en este síndrome de genes contiguos. Se presentan cinco pacientes, tres de ellos de sexo femenino, todos con los hallazgos clínicos primordiales, con rasgo facial característico de "apariencia en casco de guerrero griego", retraso en el crecimiento y del desarrollo psicomotor. Además de la deleción parcial en la región distal del brazo corto del cromosoma 4, en dos pacientes, se encontraron alteraciones genéticas adicionales, mediante el uso de microarrays de polimorfismos de nucleótido único. Se resaltan las características clínicas del síndrome de Wolf-Hirschhorn con la finalidad de orientar el diagnóstico, brindar una atención médica interdisciplinaria y, a través de su confirmación, brindar un adecuado asesoramiento genético familiar.

Main genetic entities associated with supernumerary teeth. / Principales entidades genéticas asociadas con dientes supernumerarios.

Supernumerary teeth represent a common human dental anomaly, defined as presence of extra teeth-more than the normal number foreseen in primary or permanent dentition. The prevalence has been reported between 0.2 to 3%, and is more frequent in males than females. The etiology is heterogeneous, highly variable and most of the cases are idiopathic. However, the presence of multiple impacted or erupted supernumerary teeth is rare and associated with some genetic syndromes: cleidocranial displasia, familial adenomatous polyposis, trichorhinophalangeal syndrome type I, Rubinstein-Taybi syndrome, Nance-Horan syndrome, Opitz G/BBB syndrome, oculofaciocardiodental syndrome and Robinow syndrome (autosomal dominant). The supernumerary teeth should be considered in order to possibly diagnose these entities with the aim of offering an interdisciplinary management and treatment, as well as offer adequate family genetic counseling.

Los dientes supernumerarios representan una anomalía dental frecuente en los seres humanos. Esta afección se define como la presencia de una mayor cantidad de dientes que los previstos en cuanto a los dientes de leche o a los permanentes. Según se ha notificado, la prevalencia varía entre el 0,2 % y el 3 % y es más frecuente en los varones que en las mujeres. Su etiología es heterogénea, sumamente variable y, en la mayoría de los casos, idiopática. Sin embargo, la presencia de múltiples dientes supernumerarios retenidos o erupcionados es infrecuente y está asociada con ciertos síndromes genéticos, como displasia cleidocraneal, poliposis adenomatosa familiar, síndrome tricorrinofalángico de tipo I, síndrome de Rubinstein-Taybi, síndrome de Nance-Horan, síndrome de Opitz G/BBB, síndrome oculofaciocardiodental y síndrome de Robinow (autosómico dominante). Se deben considerar los dientes supernumerarios para diagnosticar estas entidades a fin de ofrecer un abordaje interdisciplinario, además de brindar asesoramiento genético familiar adecuado.

5-α-Reductase type 2 deficiency: is there a genotype-phenotype correlation? A review.

5-α-Reductase type 2 enzyme catalyzes the conversion of testosterone into dihydrotestosterone, a potent androgen responsible for male sexual development during the fetal period and later during puberty. Its deficiency causes an autosomal recessive disorder of sex development characterized by a wide range of under-virilization of external genitalia in patients with a 46,XY karyotype. Mutations in the SRD5A2 gene cause 5-α-Reductase deficiency; although it is an infrequent disorder, it has been reported worldwide, with mutational heterogeneity. Furthermore, it has been proposed that there is no genotype-phenotype correlation, even in patients carrying the same mutation. The aim of this review was to perform an extensive search in various databases and to select those articles with a comprehensive genotype and phenotype description of the patients, classifying their phenotypes using the external masculinization score (EMS). Thus, it was possible to objectively compare the eventual genotype-phenotype correlation between them. The analysis showed that for most of the studied mutations no correlation can be established, although the specific location of the mutation in the protein has an effect on the severity of the phenotype. Nevertheless, even in patients carrying the same homozygous mutation, a variable phenotype was observed, suggesting that additional genetic factors might be influencing it. Due to the clinical variability of the disorder, an accurate diagnosis and adequate medical management might be difficult to carry out, as is highlighted in the review.

Beckwith-Wiedemann syndrome: clinical and etiopathogenic aspects of a model genomic imprinting entity. / Síndrome de Beckwith-Wiedemann: aspectos clínicos y etiopatogénicos de una entidad ejemplo de impronta genómica.

The Beckwith-Wiedemann syndrome is the most common genetic entity in overgrowth, with an approximate incidence of 1 in 10 00013 700births. Its broad clinical spectrum includes pre- and postnatal macrosomia, macroglossia, pinna abnormalities, abdominal wall defects, visceromegaly, and hyperinsulinemic hypoglycemia. This syndrome predisposes to childhood cancer and is caused by diverse genetic and/or epigenetic disorders that usually affect the regulation of genes imprinted on chromosome 11p15.5. The knowledge of (epi) genotype-phenotype correlations has prompted recommendations to propose different health care strategies, including tumor surveillance protocols based on molecular classification, aimed at standardizing clinical practice. The objective of this article is to describe the current status of the Beckwith-Wiedemann syndrome, a model of genomic imprinting.

El síndrome de Beckwith-Wiedemann es la entidad genética de sobrecrecimiento más común, con una incidencia aproximada de 1 en 10 000-13 700 nacimientos. Presenta un amplio espectro clínico, que incluye macrosomía pre- y posnatal, macroglosia, alteraciones en el pabellón auricular, defectos en la pared abdominal, visceromegalia e hipoglucemia por hiperinsulinemia. Es un síndrome de predisposición a cáncer en la infancia, causado por una variedad de alteraciones genéticas y/o epigenéticas que suelen afectar la regulación de los genes impresos en 11p15.5. Conocer las correlaciones (epi) genotipo/fenotipo ha impulsado recomendaciones para plantear las diferentes estrategias de atención, entre ellas, los protocolos de vigilancia de tumores basados en la clasificación molecular, con la finalidad de estandarizar la práctica clínica. El objetivo del presente artículo es mostrar el estado actual del síndrome de Beckwith-Wiedemann, un ejemplo de impronta genómica.

[Hallazgos clínicos y epidemiológicos en la neurofibromatosis tipo 1 y el complejo esclerosis tuberosa en una serie de pacientes pediátricos]. / Clinical and epidemiological findings in neurofibromatosis type 1 and tuberous sclerosis complex in a series of pediatric patients.

Introducción: La neurofibromatosis tipo 1 (NF1) es una entidad genética con una incidencia de 1 entre 2,500 a 3,500 nacimientos. Por su parte, el complejo esclerosis tuberosa (CET) presenta una incidencia de 1 entre 6,000 a 10,000 nacimientos. Ambas entidades neurocutáneas cursan con un patrón de herencia autosómico dominante, expresividad variable y la morbimortalidad se encuentra asociada a complicaciones multisistémicas. El objetivo de este trabajo fue exponer las características clínicas y epidemiológicas de una serie de pacientes pediátricos con diagnóstico de NF1 y CET atendidos en la Unidad de Genética Médica de la Universidad de Los Andes. Métodos: Este trabajo corresponde a una serie de casos de pacientes menores de 16 años atendidos en un período de 11 años, que cumplan con los criterios diagnósticos de NF1 y CET según los consensos para cada entidad. Resultados: Se estudiaron 89 pacientes, 73 con NF1 y 16 con CET. Presentaron dos criterios para NF1, 58 (79.45%) pacientes, y las máculas café con leche fueron las más frecuentes y presentes en todos los casos; 10 pacientes (62.50 %) presentaron dos criterios mayores para el CET, y las máculas hipocrómicas estuvieron igualmente presentes en todos los casos. Conclusiones: Este estudio muestra la forma de presentación clínica de las dos entidades neurocutáneas más frecuentes. Se discuten los criterios diagnósticos con el objeto de identificarlos a edades más tempranas y poder brindar una evaluación médica interdisciplinaria, tratamiento y un oportuno asesoramiento genético familiar. Background: Neurofibromatosis type 1 (NF1) is a genetic entity with an incidence of 1 in 2,500 to 3,500 births. Tuberous sclerosis complex (TSC) has an incidence between 1 in 6,000 to 10,000 births. Both neurocutaneous entities present an autosomal dominant inheritance pattern, variable expressivity and their morbidity and mortality is associated with multisystemic complications. The aim of this study was to present the clinical and epidemiological characteristics of a series of pediatric patients diagnosed with NF1 and TSC, who were treated in the Medical Genetics Unit of the Universidad of Los Andes. Methods: This work corresponds to a series of cases of patients under 16 years of age served in a period of 11 years, who met the diagnostic criteria of NF1 and CET according to the consensus for each entity. Results: We studied 89 patients, 73 with NF1 and 16 with TSC. 58 (79.45%) of the patients presented two criteria for NF1, with café-au-lait macules being the most frequent and present in all cases. 10 (62.50%) of the patients presented two major criteria for TSC; hypochromic macules were equally present in all cases. Conclusions: This study shows the clinical presentation of the two most frequent neurocutaneous entities. Diagnostic criteria are discussed in order to perform them at younger ages and to provide an interdisciplinary medical evaluation, treatment and timely family genetic counseling.

[Isotretinoin embryopathy: An entity that can be avoided]. / Embriopatía por isotretinoína: Una entidad que puede evitarse.

Isotretinoin is the most effective drug in the treatment of severe recalcitrant nodulocystic acne. However, treatment with this drug is associated with adverse effects, the most severe being teratogenesis. It has been estimated that 40% of pregnancies exposed to isotretinoin present spontaneous abortion and 35% develop embryopathy. We present the case of a newborn with a history of prenatal exposure to isotretinoin, a clinical entity that can be avoided, with severe congenital defects in the central nervous system and important facial dysmorphisms, with unfavorable clinical course.

La isotretinoína es el medicamento más efectivo en el tratamiento del acné noduloquístico recalcitrante grave. Sin embargo, el tratamiento con este fármaco se encuentra asociado con efectos adversos, y el más grave es la teratogénesis. Se ha estimado que 40% de los embarazos expuestos a isotretinoína presenta un aborto espontáneo y 35% desarrolla embriopatía. Se presenta el caso de un recién nacido con antecedente de exposición prenatal a isotretinoína, una entidad clínica que puede evitarse, con graves defectos congénitos en el sistema nervioso central e importantes dismorfias faciales, con evolución clínica desfavorable.

[Clinical and molecular study in a family with cleidocranial dysplasia]. / Estudio clínico y molecular en una familia con displasia cleidocraneal.

Cleidocranial dysplasia is an uncommon bone dysplasia with an autosomal dominant inheritance pattern characterized by short stature, large fontanels, midface hypoplasia, absence or hypoplasia of clavicles and orodental alterations. This is Estudio clínico y molecular en una familia con displasia cleidocraneal Clinical and molecular study in a family with cleidocranial dysplasia produced by mutations in the RUNX2 gene located at 6p21.1. We report two male adolescents (cousins), with cleidocranial dysplasia who presented a heterozygous missense mutation (c.674G> A, p.R225Q) in the RUNX2 gene, characterized by severe phenotype, such as absent clavicles, but with variation in the delayed fontanel closure, dental abnormalities (anomalies in shape and number) and scoliosis, thus demonstrating intrafamilial variation in these patients with the same genotype.

La displasia cleidocraneal es una displasia ósea infrecuente con patrón de herencia autosómico dominante, que se caracteriza por presentar talla baja, fontanelas amplias, hipoplasia mediofacial, ausencia o hipoplasia de clavículas y alteraciones orodentales. Es producida por mutaciones en el gen RUNX2 localizado en 6p21.1. Se presentan dos adolescentes masculinos (primos hermanos) con displasia cleidocraneal, los cuales mostraron mutación heterocigota, cambio de sentido (c.674G>A, p.R225Q) en el gen RUNX2, caracterizados por presentar fenotipo grave, como ausencia de clavículas, pero con variación en el retardo en el cierre de fontanelas, alteraciones dentales (anomalías en forma y número) y escoliosis, por lo que se demuestra la variación intrafamiliar en estos pacientes con el mismo genotipo.

[Mosaic trisomy 18. Series of cases]. / Trisomía 18 en mosaico. Serie de casos.

Trisomy 18 syndrome (T18) is a clinical and genetic disorder, which has a full extra chromosome 18 in each cell, variant that is called free trisomy. In addition, it can occur in partial and mosaic form. It is characterized by intrauterine growth restriction, psychomotor and mental retardation, characteristic craniofacial findings, congenital heart disease, hypoplastic pelvis, clenched hand and rocker-bottom foot, among others. The mosaic T18 occurs when cells with T18 and normal cell lines exist in the same individual and correspond to 5% of cases. Trisomía 18 en mosaico. Serie de casos Mosaic trisomy 18. Series of cases The phenotypic findings are highly variable and no correlation was evident between the percentage of trisomic cells and the findings found. The aim of this report is to present a series of five cases of mosaic T18 with emphasis on clinical aspects in order to guide an interdisciplinary adequate medical care and provide timely genetic counseling.

El síndrome de la trisomía 18 es un trastorno clínico y genético, el cual presenta un cromosoma 18 extra completo en cada célula, variante que se denomina trisomía libre. Además, puede ocurrir en la forma parcial y mosaico. Clínicamente, se caracteriza por retardo del crecimiento intrauterino, del desarrollo psicomotor y mental, hallazgos craneofaciales característicos, cardiopatía congénita, pelvis hipoplásica, manos empuñadas y pies en mecedora, entre otros. La trisomía 18 en mosaico se presenta cuando células con trisomía del cromosoma 18 y líneas celulares normales existen en un mismo individuo, y corresponde al 5% de los casos. Los hallazgos fenotípicos son muy variables y no se evidencia una correlación entre el porcentaje de células trisómicas y los hallazgos encontrados. El objetivo de este informe es presentar una serie de cinco casos de trisomía 18 en mosaico. Se hace énfasis en los aspectos clínicos con la finalidad de orientar una adecuada atención médica interdisciplinaria y brindar un oportuno asesoramiento genético.

Osteochondroma of mandibular ramus and condylar neck: simultaneous resection and reconstruccion with personalized alloplastic joint prosthesis / Osteocondroma de la rama mandibular y cuello del cóndilo: resección y reconstrucción simultánea con prótesis articular personalizada aloplástica

Osteochondromas are benign osteogenic tumors that can attain great size, which may require resection and additional treatment to restore the jaw's shape and function. In this report, an osteochondroma located on the mandibular ramus and neck of the condyle was resected and reconstructed simultaneously through a total joint replacement. After the surgery, the patient remains asymptomatic and recovers opening and closing ranges, phonation and the masticatory function. The immediate reconstruction after resection is a good alternative to avoid a second operation and the presurgical virtual planning ensures the complete removal of the lesion using cutting guides and covering the entire defect with a customized alloplastic joint prosthesis.

Los osteocondromas son tumores osteogénicos benignos que pueden alcanzar grandes tamaños, los cuales requieren de resección quirúrgica y generalmente de algún tratamiento adicional para restaurar la forma y la función mandibular. En este caso, un osteocondroma localizado en la rama mandibular y el cuello del cóndilo fue reseccionado y reconstruido simultáneamente a través de un reemplazo articular total. Después de la cirugía, el paciente permanece asintomático y recupera los intervalos de apertura y cierre, la fonación y la función masticatoria. La reconstrucción inmediata después de la resección es una buena alternativa para evitar una segunda operación, y la planificación virtual prequirúrgica garantiza la eliminación completa de la lesión utilizando guías de corte y cubriendo todo el defecto con una prótesis articular aloplástica personalizada.

Hallazgos clínicos, bioquímicos y moleculares de la acidemia propiónica / Clinical, biochemical and molecular findings of propionic acidemia

La acidemia propiónica es un trastorno infrecuente con patrón de herencia autosómico recesivo causado por la deficiencia de la enzima mitocondrial propionil-CoA carboxilasa, que convierte el propionil-CoA a D-metilmalonil-CoA. Se expone el caso de un recién nacido masculino con signos de dificultad respiratoria, vómitos y cansancio durante la alimentación. Presentó acidosis metabólica, cuerpos cetónicos en el suero y la orina positivos, hiperamonemia, anemia, trombocitopenia e hipoproteinemia. El estudio bioquímico por cromatografía de gases acoplada a espectrometría de masas en la muestra de orina fue sugestivo de acidemia propiónica. El estudio molecular en el gen PCCA encontró las mutaciones c.893A>G (p.K298R) en el padre y c.937C>T (p.R313X) en la madre. Existe la necesidad de establecer el diagnóstico de esta entidad infrecuente para implementar las medidas terapéuticas disponibles y aportar el oportuno asesoramiento genético.

Propionic acidemia is an infrequent disorder with an autosomal recessive inheritance pattern caused by the deficiency of the mitochondrial enzyme propionyl-CoA carboxylase that converts propionyl-CoA to D-methylmalonyl-CoA. We present the case of a male newborn who showed signs of respiratory distress, vomiting and tiredness during feeding. He presented metabolic acidosis, positive serum and urine ketone bodies, hyperammonemia, anemia, thrombocytopenia and hypoproteinemia. The biochemical study by gas chromatography coupled to mass spectrometry in a urine sample was suggestive of propionic acidemia. The molecular study in the PCCA gene found the mutations c.893A>G (p.K298R) in the father and c.937C> T (p.R313X) in the mother. There is a need to establish the diagnosis of this infrequent entity to implement the therapeutic measures available and provide the appropriate genetic counseling.