PALB2 germline mutations in a multi-gene panel testing cohort of 1905 breast-ovarian cancer patients in Argentina.

PURPOSE: PALB2 variants have been scarcely described in Argentinian and Latin-American reports. In this study, we describe molecular and clinical characteristics of PALB2 mutations found in multi-gene panels (MP) from breast-ovarian cancer (BOC) families in different institutions from Argentina. METHODS: We retrospectively identified PALB2 pathogenic (PV) and likely pathogenic (LPV) variants from a cohort of 1905 MP results, provided by one local lab (Heritas) and SITHER (Hereditary Tumor Information System) public database. All patients met hereditary BOC clinical criteria for testing, according to current guidelines. RESULTS: The frequency of PALB2 mutations is 2.78% (53/1905). Forty-eight (90.5%) are PV and five (9.5%) are LPV. Most of the 18 different mutations (89%) are nonsense and frameshift types and 2 variants are novel. One high-rate recurrent PV (Y551*) is present in 43% (23/53) of the unrelated index cases. From the 53 affected carriers, 94% have BC diagnosis with 14% of bilateral cases. BC phenotype is mainly invasive ductal (78%) with 62% of hormone-receptor positive and 22% of triple negative tumors. Self-reported ethnic background of the cohort is West European (66%) and native Latin-American (20%) which is representative of Buenos Aires and other big urban areas of the country. CONCLUSION: This is the first report describing molecular and clinical characteristics of PALB2 carriers in Argentina. Frequency of PALB2 PV in Argentinian HBOC families is higher than in other reported populations. Y551* is a recurrent mutation that seems to be responsible for almost 50% of PALB2 cases.

A novel interstitial deletion of 2q22.3 q23.3 in a patient with dysmorphic features, epilepsy, aganglionosis, pure red cell aplasia, and skeletal malformations.

Many chromosomal deletions encompassing the 2q23.1 region have been described ranging from small deletions of 38 kb up to >19 Mb. Most phenotypic features of the 2q23.1 deletion syndrome are due to a MBD5 gene loss independent of the size of the deletion. Here, we describe a male patient harboring a novel interstitial deletion encompassing the 2q22.3 q23.3 chromosomal region. Array-CGH revealed a 7.1 Mb deletion causing haploinsufficiency of several genes including MBD5, ACVR2, KIF5C, and EPC2. This patient presents with additional findings to those already described in individuals who have deletions of MBD5 including toes absence of halluces, pure red cell aplasia, and intestinal aganglionosis. Interestingly, in the deleted region there are previously identified regulatory sequences which are located upstream to ZEB2, which is associated with Hirschsprung disease (HSCR). Several genes have been associated with pure red cell aplasia, but to our knowledge, this is the first time that 2q deletion is associated with this phenotype. These additional findings should be added to the list of manifestations associated with 2q deletion, and provide support for the hypothesis that this individual has a true contiguous gene deletion syndrome.

Dysphagia, melanosis, gastrointestinal stromal tumors and a germinal mutation of the KIT gene in an Argentine family.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymatous neoplasms of the human digestive tract. They locate preferentially in stomach, duodenum or small bowel. Usually sporadic, familial cases unrelated to neurofibromatosis may be due to germline mutations in KIT or PDGFRA. We describe the first Argentine family with GIST in which we found, diffuse cutaneous melanosis, lentiginosis, and dysphagia. Dysphagia was not observed in the four families previously described with the same mutation. Histopathology resulted consistent with GIST, and tumor immunohistochemistry was likewise positive for DOG-1, CD117 (KIT) and CD34. The search for germline mutations identified the KIT c.1697T > C (p.559V > A) substitution in exon 11. Treatment with imatinib is furnishing positive results.

First report in Argentina of a pathogenic DMP1 variant associated with autosomal recessive hypophosphatemic rickets. / Primer reporte en Argentina de variante patógena en DMP1 asociada a raquitismo hipofosfatémico autosómico recesivo.

Hereditary hypophosphatemic rickets is a genetic condition associated with impaired bone mineralization caused by phosphate deficiency. It results in skeletal deformity and growth retardation in early childhood. Different inheritance patterns have been described according to the locus involved. Given the phenotypic overlapping and the difficulty in analyzing reduced genealogies, molecular studies are important to establish the genetic cause and implement a family-centered approach. The autosomal recessive form of hypophosphatemic rickets (ARHR, OMIM 241520) is an extremely rare condition reported in families of European and Middle Eastern descent. Loss-of-function mutations in the DMP1 (dentin matrix acidic phosphoprotein 1) gene are associated with hereditary hypophosphatemic rickets type 1. In this article, we describe the first report of an Argentine family with hereditary hypophosphatemic rickets due to a mutation in the DMP1 gene.

El raquitismo hipofosfatémico hereditario es una condición genética asociada con una mineralización ósea alterada causada por la deficiencia de fosfato. Produce deformidad esquelética y retraso del crecimiento en la infancia. Se describen diferentes patrones de herencia según el locus involucrado. Dado el solapamiento de los fenotipos y la dificultad en analizar genealogías reducidas, los estudios moleculares son importantes para establecer la causa genética y realizar el abordaje familiar. La forma recesiva del raquitismo hipofosfatémico (ARHR, OMIM #241520) es una condición extremadamente poco frecuente reportada en familias de origen europeo y de Oriente Medio. Las mutaciones con pérdida de función del gen DMP1 (dentin matrix acidic phosphoprotein 1) se asocian al raquitismo hipofosfatémico hereditario tipo 1. En este artículo presentamos el primer reporte de una familia argentina con raquitismo hipofosfatémico hereditario por mutación en DMP1.

Nationwide genetic analysis of more than 600 families with inherited eye diseases in Argentina.

This study corresponds to the first large-scale genetic analysis of inherited eye diseases (IED) in Argentina and describes the comprehensive genetic profile of a large cohort of patients. Medical records of 22 ophthalmology and genetics services throughout 13 Argentinian provinces were analyzed retrospectively. Patients with a clinical diagnosis of an ophthalmic genetic disease and a history of genetic testing were included. Medical, ophthalmological and family history was collected. A total of 773 patients from 637 families were included, with 98% having inherited retinal disease. The most common phenotype was retinitis pigmentosa (RP, 62%). Causative variants were detected in 379 (59%) patients. USH2A, RPGR, and ABCA4 were the most common disease-associated genes. USH2A was the most frequent gene associated with RP, RDH12 early-onset severe retinal dystrophy, ABCA4 Stargardt disease, PROM1 cone-rod dystrophy, and BEST1 macular dystrophy. The most frequent variants were RPGR c.1345 C > T, p.(Arg449*) and USH2A c.15089 C > A, p.(Ser5030*). The study revealed 156/448 (35%) previously unreported pathogenic/likely pathogenic variants and 8 possible founder mutations. We present the genetic landscape of IED in Argentina and the largest cohort in South America. This data will serve as a reference for future genetic studies, aid diagnosis, inform counseling, and assist in addressing the largely unmet need for clinical trials to be conducted in the region.

iPSC-Derived Intestinal Organoids from Cystic Fibrosis Patients Acquire CFTR Activity upon TALEN-Mediated Repair of the p.F508del Mutation.

Cystic fibrosis (CF) is the main genetic cause of death among the Caucasian population. The disease is characterized by abnormal fluid and electrolyte mobility across secretory epithelia. The first manifestations occur within hours of birth (meconium ileus), later extending to other organs, generally affecting the respiratory tract. It is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CFTR encodes a cyclic adenosine monophosphate (cAMP)-dependent, phosphorylation-regulated chloride channel required for transport of chloride and other ions through cell membranes. There are more than 2,000 mutations described in the CFTR gene, but one of them, phenylalanine residue at amino acid position 508 (p.F508del), a recessive allele, is responsible for the vast majority of CF cases worldwide. Here, we present the results of the application of genome-editing techniques to the restoration of CFTR activity in p.F508del patient-derived induced pluripotent stem cells (iPSCs). Gene-edited iPSCs were subsequently used to produce intestinal organoids on which the physiological activity of the restored gene was tested in forskolin-induced swelling tests. The seamless restoration of the p.F508del mutation resulted in normal expression of the mature CFTR glycoprotein, full recovery of CFTR activity, and a normal response of the repaired organoids to treatment with two approved CF therapies: VX-770 and VX-809.

Seasonality of Rotavirus Hospitalizations at Costa Rica's National Children's Hospital in 2010-2015.

Rotavirus is a leading cause of acute diarrhea in children worldwide. Costa Rica recently started universal rotavirus vaccinations for infants with a two-dose schedule in February 2019. We aimed to study the seasonality of rotavirus during the pre-vaccination era. We retrospectively studied a six-year period of hospital admissions due to rotavirus gastroenteritis. We estimated seasonal peak timing and relative intensities using trend-adjusted negative binomial regression models with the δ-method. We assessed the relationship between rotavirus cases and weather characteristics and estimated their effects for the current month, one-month prior and two months prior, by using Pearson correlation coefficients. A total of 798 cases were analyzed. Rotavirus cases predominated in the first five months of the year. On average, the peak of admissions occurred between late-February and early-March. During the seasonal peaks, the monthly count tended to increase 2.5-2.75 times above the seasonal nadir. We found the strongest negative association of monthly hospitalizations and joint percentiles of precipitation and minimal temperature at a lag of two months (R = -0.265, p = 0.027) and we detected correlations of -0.218, -0.223, and -0.226 (p < 0.05 for all three estimates) between monthly cases and the percentile of precipitation at lags 0, 1, and 2 months. In the warm tropical climate of Costa Rica, the increase in rotavirus hospitalizations coincided with dry and cold weather conditions with a two-month lag. The findings serve as the base for predictive modeling and estimation of the impact of a nation-wide vaccination campaign on pediatric rotaviral infection morbidity.

Primer reporte en Argentina de variante patógena en DMP1 asociada a raquitismo hipofosfatémico autosómico recesivo / First report in Argentina of a pathogenic DMP1 variant associated with autosomal recessive hypophosphatemic rickets

El raquitismo hipofosfatémico hereditario es una condición genética asociada con una mineralización ósea alterada causada por la deficiencia de fosfato. Produce deformidad esquelética y retraso del crecimiento en la infancia. Se describen diferentes patrones de herencia según el locus involucrado. Dado el solapamiento de los fenotipos y la dificultad en analizar genealogías reducidas, los estudios moleculares son importantes para establecer la causa genética y realizar el abordaje familiar. La forma recesiva del raquitismo hipofosfatémico (ARHR, OMIM #241520) es una condición extremadamente poco frecuente reportada en familias de origen europeo y de Oriente Medio. Las mutaciones con pérdida de función del gen DMP1 (dentin matrix acidic phosphoprotein 1) se asocian al raquitismo hipofosfatémico hereditario tipo 1. En este artículo presentamos el primer reporte de una familia argentina con raquitismo hipofosfatémico hereditario por mutación en DMP1

Hereditary hypophosphatemic rickets is a genetic condition associated with impaired bone mineralization caused by phosphate deficiency. It results in skeletal deformity and growth retardation in early childhood. Different inheritance patterns have been described according to the locus involved. Given the phenotypic overlapping and the difficulty in analyzing reduced genealogies, molecular studies are important to establish the genetic cause and implement a family-centered approach. The autosomal recessive form of hypophosphatemic rickets (ARHR, OMIM 241520) is an extremely rare condition reported in families of European and Middle Eastern descent. Loss-of-function mutations in the DMP1 (dentin matrix acidic phosphoprotein 1) gene are associated with hereditary hypophosphatemic rickets type 1. In this article, we describe the first report of an Argentine family with hereditary hypophosphatemic rickets due to a mutation in the DMP1 gene.

Derivative chromosomes involving 5p large rearranged segments went unnoticed with the use of conventional cytogenetics.

BACKGROUND: In countries where comparative genomic hybridization arrays (aCGH) and next generation sequencing are not widely available due to accessibility and economic constraints, conventional 400-500-band karyotyping is the first-line choice for the etiological diagnosis of patients with congenital malformations and intellectual disability. Conventional karyotype analysis can rule out chromosomal alterations greater than 10 Mb. However, some large structural abnormalities, such as derivative chromosomes, may go undetected when the analysis is performed at less than a 550-band resolution and the size and banding pattern of the interchanged segments are similar. Derivatives frequently originate from inter-chromosomal exchanges and sometimes are inherited from a parent who carries a reciprocal translocation. CASE PRESENTATION: We present two cases with derivative chromosomes involving a 9.1 Mb 5p deletion/14.8 Mb 10p duplication in the first patient and a 19.9 Mb 5p deletion/ 18.5 Mb 9p duplication in the second patient. These long chromosomal imbalances were ascertained by aCGH but not by conventional cytogenetics. Both patients presented with a deletion of the Cri du chat syndrome region and a duplication of another genomic region. Each patient had a unique clinical picture, and although they presented some features of Cri du chat syndrome, the phenotype did not conclusively point towards this diagnosis, although a chromosomopathy was suspected. CONCLUSIONS: These cases highlight the fundamental role of the clinical suspicion in guiding the approach for the etiological diagnosis of patients. Molecular cytogenetics techniques, such as aCGH, should be considered when the clinician suspects the presence of a chromosomal imbalance in spite of a normal karyotype.

Genetic Imbalances in Argentinean Patients with Congenital Conotruncal Heart Defects.

Congenital conotruncal heart defects (CCHD) are a subset of serious congenital heart defects (CHD) of the cardiac outflow tracts or great arteries. Its frequency is estimated in 1/1000 live births, accounting for approximately 10⁻30% of all CHD cases. Chromosomal abnormalities and copy number variants (CNVs) contribute to the disease risk in patients with syndromic and/or non-syndromic forms. Although largely studied in several populations, their frequencies are barely reported for Latin American countries. The aim of this study was to analyze chromosomal abnormalities, 22q11 deletions, and other genomic imbalances in a group of Argentinean patients with CCHD of unknown etiology. A cohort of 219 patients with isolated CCHD or associated with other major anomalies were referred from different provinces of Argentina. Cytogenetic studies, Multiplex-Ligation-Probe-Amplification (MLPA) and fluorescent in situ hybridization (FISH) analysis were performed. No cytogenetic abnormalities were found. 22q11 deletion was found in 23.5% of the patients from our cohort, 66% only had CHD with no other major anomalies. None of the patients with transposition of the great vessels (TGV) carried the 22q11 deletion. Other 4 clinically relevant CNVs were also observed: a distal low copy repeat (LCR)D-E 22q11 duplication, and 17p13.3, 4q35 and TBX1 deletions. In summary, 25.8% of CCHD patients presented imbalances associated with the disease.

[Double aneuploidy: Klinefelter and Edwards syndromes (48,XXY,+18). Case report]. / Doble aneuploidía: síndromes de Klinefelter y Edwards (48,XXY,+18). Reporte de caso.

The co-existence of a double chromosomal abnormality in one individual is a rare event, even more the simultaneous presence of Klinefelter (XXY) and Edwards (trisomy 18) syndrome. The aim of this article is to report the case of a newborn with a double aneuploidy, which consists in the coexistence of Edwards and Klinefelter syndrome. The patient's phenotype correlates mainly with Edwards syndrome. The diagnosis is made by performing the cytogenetics (karyotype) of peripheral blood lymphocytes. Only 15 cases of patients with Klinefelter and Edwards syndromes had been reported in literature so far.

La existencia de una doble aneuploidía en un mismo individuo es una anomalía cromosómica poco frecuente que involucra, mayoritariamente, al par sexual y al cromosoma 21. En el presente artículo, se expone el caso clínico de un niño con la doble aneuploidía 48,XXY,+18. El fenotipo del paciente era coincidente con el síndrome de Edwards. El diagnóstico se efectuó mediante la realización del estudio citogenético de linfocitos de sangre periférica. En la bibliografía revisada, solo se han encontrado 15 casos reportados de pacientes con síndromes de Klinefelter y Edwards.

7p15 deletion as the cause of hand-foot-genital syndrome: a case report, literature review and proposal of a minimum region for this phenotype.

BACKGROUND: Hand-foot-genital syndrome (HFGS) is a rare condition characterized by congenital malformations in the limbs and genitourinary tract. Generally, this syndrome occurs due to point mutations that cause loss of function of the HOXA13 gene, which is located on 7p15; however, there are some patients with HFGS caused by interstitial deletions in this region. CASE PRESENTATION: We describe a pediatric Mexican patient who came to the Medical Genetics Department at the National Institute of Pediatrics because he presented with genital, hand and feet anomalies, facial dysmorphisms, and learning difficulties. Array CGH reported a 12.7 Mb deletion that includes HOXA13. CONCLUSIONS: We compared our patient with cases of HFGS reported in the literature caused by a microdeletion; we found a minimum shared region in 7p15.2. By analyzing the phenotype in these patients, we suggest that microdeletions in this region should be investigated in all patients with clinical characteristics of HFGS who also present with dysplastic ears, mainly low-set implantation with a prominent antihelix, as well as a low nasal bridge and long philtrum.

Spectrum of BRCA1/2 variants in 940 patients from Argentina including novel, deleterious and recurrent germline mutations: impact on healthcare and clinical practice.

BRCA1/2 mutations in Latin America are scarcely documented and in serious need of knowledge about the spectrum of BRCA pathogenic variants, information which may alter clinical practice and subsequently improve patient outcome. In addition, the search for data on testing policies in different regions constitutes a fundamental strength for the present study, which analyzes BRCA1/2 gene sequences and large rearrangements in 940 probands with familial and/or personal history of breast/ovary cancer (BOC). In non-mutated DNA samples, Multiplex Ligation-dependent Probe Amplification assays (MLPA) were used for the analysis of large rearrangements. Our studies detected 179 deleterious mutations out of 940 (19.04%) probands, including 5 large rearrangements and 22 novel mutations. The recurrent mutations accounted for 15.08% of the total and only 2.87% of the probands analyzed, very different from a Hispanic panel previously described. IN CONCLUSION: a) this first comprehensive description of the spectrum in BRCA1/2 sheds light on the low frequency of recurrent mutations; b) this information is key in clinical practice to select adequate sequencing studies in our population, subsequently improve patient outcome and prevent damage associated to false normal reports resulting from the use of invalid population panels; c) panels of mutations from other populations should be cautiously validated before imported, even those of apparently similar origin, a concept to be considered beyond significance in Argentina.

Identification and characterization of four splicing variants of ovine POU1F1 gene.

Expression of POU1F1 gene, a member of the POU homeodomain family of transcription factors, is necessary for normal differentiation, development and survival of three anterior pituitary cell types (thyrotrophs, somatotrophs and lactotrophs) and for the proper expression of growth hormone (GH), prolactin (PRL), thyroid-stimulating hormone (TSH) genes and POU1F1 gene itself. Alternative splicing forms of this gene have been reported in different species, with few functional studies. Apart from the POU1F1-Wild-type with the expected length, in this work we isolated three additional splicing variants: POU1F1-beta, with a 78 bp insert in the trans-activation domain; POU1F1-gamma that lacks exon 3 and POU1F1-delta that lacks exons 3, 4 and 5. Four different protein isoforms were also detected by Western blot in the sheep pituitary tissue. Functional assays were performed to study the trans-activation of GH and PRL promoters by the splicing variants. Regarding the PRL promoter, the beta variant presented only 12% of the Wild-type trans-activation capacity. Variants gamma and delta showed no capacity to trans-activate PRL promoter. Both gamma and delta variants acted as repressors of Wt, reducing significantly the trans-activation made by Wt alone (p<0.05). Concerning the GH promoter, the beta variant presented a trans-activation capacity 10% higher than Wt. Wt and beta variants strongly interact in the activation of GH promoter doubling the trans-activation potential of Wt. Variants gamma and delta showed no capacity to trans-activate the GH promoter and both acted as repressors, reducing significantly (p<0.001) the trans-activation performed by Wt. This work presents, for the first time, the characterization of four splicing forms of Ovis aries POU1F1 gene.

A combined approach for gene discovery identifies insulin-like growth factor-binding protein-related protein 1 as a new gene implicated in human endometrial receptivity.

In the past, human endometrial receptivity has been investigated by chasing specific molecules throughout the menstrual cycle. Now the genomic approach allows us to investigate the hierarchical contribution of a high number of genes to a specific function. In this study, we analyzed differentially the gene expression pattern of 375 human cytokines, chemokines, and related factors, plus that of their receptors, in endometrial receptivity. To do this, we used a combined approach of human endometrium and cell lines. We have compared the gene expression pattern in receptive vs. prereceptive human endometria and contrasted the results with gene expression in the highly adhesive cell line (to JAR cells and mouse blastocysts) RL95-2 vs. HEC-1A, a cell line with markedly less adhesiveness. IGF-binding protein-related protein 1 (IGFBP-rP1), also known as IGFBP-7/mac 25, was the second most up-regulated gene in both of the investigated models. These results were corroborated by performing RT-PCR on the same RNA samples and validated by quantitative fluorescent RT-PCR and in situ hybridization in endometrium throughout the menstrual cycle. Interestingly, a 35-fold increase in expression during the receptive phase was compared with the prereceptive phase followed by a sharp increase in the late luteal. Further quantitative fluorescent RT-PCR experiments using the epithelial and stromal endometrial fraction throughout the menstrual cycle confirmed that IGFBP-rP1 expression was localized in the epithelial and stromal compartments and up-regulated mainly in the latter. In situ experiments confirmed the endometrial localization and regulation of IGFBP-rP1 mRNA. At the protein level, IGFBP-rP1 was localized by immunohistochemistry at the apical part of the luminal and glandular epithelium, stromal, and endothelial cells. In conclusion, using a genomic approach with a combined experimental design of receptivity in vivo and in vitro, we have discovered the implication of IGFBP-rP1 in endometrial physiology, which seems related to endometrial receptivity.

Human endometrial receptivity: gene regulation.

Endometrial receptivity is a self-limited period in which the endometrial epithelium (EE) acquires a functional and transient ovarian steroid-dependent status that allows blastocyst adhesion. Termed as "the window of implantation", this specific period opens 4-5 days after progesterone production or administration and closes after 9-10 days. Scientific knowledge on the endometrial receptivity process is fundamental for the understanding of human reproduction, but so far none of the proposed biochemical markers for endometrial receptivity has been proven to be clinically useful. In this work, we present strategies of cDNA analysis technologies that aim to clarify the fragmented information in this field. Specifically, the objective is the differential identification, cloning and sequencing of genes linked to endometrial receptivity in humans, combining differential display PCR and cDNA microarray analysis of endometrial epithelial-derived cell lines and endometrial samples obtained in the same patient 2 and 7 days after the luteinizing hormone (LH) surge (day LH+2) and (day LH+7), respectively.

Acercamiento a la vida y obra del Doctor Jorge Ángel Pérez Toscano / An approach to the life and work of Doctor Jorge Ángel Pérez Toscano

Se profundizó sobre la vida del médico colombino ya fallecido Jorge Ángel Pérez Toscano con el objetivo de destacar toda su entrega a la medicina. De procedencia humilde, graduado de Doctor en Medicina en diciembre de 1974. Director del área de salud del Policlínico de San Pedro de Mayabón. Subdirector docente en el Hospital Territorial Dr. Mario Muñoz Monroy por algunos años de trabajo, jefe y fundador del servicio de especialidades, muchos lo recuerdan por sus adecuados métodos de trabajo, por la gran prevalencia de sus condiciones humanas, su preocupación ante el dolor ajeno. Dejó su huella en el Hospital Mario Muñoz Monroy. Ocupó responsablemente altos cargos de dirección. Ejerció su profesión dignamente y a conciencia; veló siempre por la salud de sus pacientes consagrando su vida al servicio de la humanidad (AU).

The life of the deceased doctor Jorge Angel Perez Toscano, from Colon, was deepened with the objective of highlighting his commitment to Medicine. Of humble origins, he graduated as Doctor in Medicine on December 1974; Doctor Perez Toscano was the director of the San Pedro de Mayabon Policlinic, then he was the teaching sub-director of the Territorial Hospital "Mario Muñoz Monroy" of Colon, and the Head and founder of the service of Specialties. Many people remember him because of his appropriate methods of work, the great prevalence of his human conditions and his concern with the pain of others. He left his imprint in the Hospital "Mario Muñoz Monroy" and responsibly held senior management positions. He consecrated his life to the service of the humankind, consciously and honorably practicing his profession, and looking always after his patients´ health (AU).

Doble aneuploidía: síndromes de Klinefelter y Edwards (48, XXY, +18). Reporte de caso / Double aneuploidy: Klinefelter and Edwards syndromes (48, XXY, +18). Case report

La existencia de una doble aneuploidía en un mismo individuo es una anomalía cromosómica poco frecuente que involucra, mayoritariamente, al par sexual y al cromosoma 21. En el presente artículo, se expone el caso clínico de un niño con la doble aneuploidía 48,XXY,+18. El fenotipo del paciente era coincidente con el síndrome de Edwards. El diagnóstico se efectuó mediante la realización del estudio citogenético de linfocitos de sangre periférica. En la bibliografía revisada, solo se han encontrado 15 casos reportados de pacientes con síndromes de Klinefelter y Edwards.

The co-existence of a double chromosomal abnormality in one individual is a rare event, even more the simultaneous presence of Klinefelter (XXY) and Edwards (trisomy 18) syndrome. The aim of this article is to report the case of a newborn with a double aneuploidy, which consists in the coexistence of Edwards and Klinefelter syndrome. The patient's phenotype correlates mainly with Edwards syndrome. The diagnosis is made by performing the cytogenetics (karyotype) of peripheral blood lymphocytes. Only 15 cases of patients with Klinefelter and Edwards syndromes had been reported in literature so far.