Double aneuploidy in a 2-month-old male with Edward syndrome and Klinefelter syndrome: a case report.

Introduction and importance: Edward syndrome is a severe chromosomal defect that occurs as a result of non-disjunction through meiosis. It presents with cardiac septal defects, horseshoe kidneys, patent ductus arteriosus, central nervous system dysgenesis, distinctive craniofacial deformities, and overriding or overlapping fingers. Klinefelter syndrome (47, XXY) is found in 1 in 660 newborn males. It is considered to be one of the most common genetic causes of infertility. It manifests with small firm testes, androgen insufficiency, and azoospermia. Case presentation: A 2-month-old male infant with a history of weakness in feeding, frequent convulsions, and an increase in cyanosis two days ago. There were multiple skeletal deformities and a tendency to spasm in the extremities, left ventricular atrophy, mitral atresia, atrial septal defect, ventricular septal defect with dilated right cavities, tricuspid valve regurgitation, pulmonary valve stenosis; and the aorta exits in the right ventricle. There is a widening of the subdural space, which was observed in the left frontal-parietal side with cortical atrophy in that area and a widening of the Sylvian fissure. A karyotype test confirmed the presence of Edward and Klinefelter syndromes. Clinical discussion: Aneuploidy is a chromosomal issue characterized by an abnormal number of a chromosome copies. The coexistence of two aneuploidies is called "double aneuploidy" which is a rare occurrence. Herein, we report a case of a 2-month-old male with Edward syndrome and Klinefelter syndrome. Conclusion: This publication aims to highlight the challenges in diagnosing and treating a complicated genetic disease.

When Fryn met Edward: Two rare syndromes in a single patient.

A neonate born at our centre was diagnosed as Fryns Syndrome ie congenital diaphragmatic hernia with facial dysmorphism and distal limb anomalies, which is a rare disorder with only a few hundred cases reported till date.With high clinical index of suspicion and further evaluation, the diagnosis was confirmed. The baby was initially stabilized and later underwent repair of the diaphragmatic hernia. Despite best measures, the baby could not be salvaged. When severe, this can be lethal and diagnosis can only be made after autopsy. However, with early suspicion, better modalities of investigations available and improved NICU care, these babies can be salvaged. We report a case of Fryns Syndrome who was incidentally found to have Edward Syndrome as well. Such an extremely rare combination is yet to be reported in medical literature.Also with updated genetic studies, better diagnostics and treatment options coming up in future, there are chances to improve the survivability of these babies. It is prudent to document all such cases to aid in better understanding of the disease process.

Direct hyperbilirubinemia and cholestasis in trisomy 13 and 18.

Trisomy 13 and 18 are common chromosomal abnormalities that affect multiple organ systems. There is a paucity of published data, however, on the hepatic complications seen in these patient populations. One of the most common pathologic hepatobiliary issues seen in the newborn period is direct hyperbilirubinemia (DH). Thus, this study sought to estimate the incidence and evaluate possible etiologies of DH in neonates with trisomy 13 or 18. This retrospective cohort study included all infants admitted to our two neonatal intensive care units between 2012 and 2020 with the diagnosis of trisomy 13 or 18. DH is most commonly diagnosed as a direct bilirubin >1 mg/dl but a cutoff of >2 mg/dl is more specific for cholestasis, so both cutoffs were evaluated. Continuous data were compared using Fisher's exact test and categorical variables by the Mann-Whitney U test. Thirty-five patients met inclusion: 13 with trisomy 13 and 22 with trisomy 18. DH of >2 mg/dl was seen in seven (53.8%) patients with trisomy 13 and five (22.7%) with trisomy 18. Using a cutoff of >1 mg/dl, the rate of trisomy 13 was unchanged, but the rate in trisomy 18 increased to 9/22 (40.9%). There was a trend toward more DH in trisomy 13 patients (p = 0.079) versus trisomy 18 and higher rates in infants who received total parenteral nutrition (TPN) (50.0 vs. 13.3%, p = 0.026). The presence of cardiac or ultrasound-defined hepatobiliary abnormalities was not correlated with DH. Due to the high rates of DH in hospitalized neonates with trisomy 13 and 18, we recommend screening newborns with trisomy 13 or 18 for DH starting in the first week of life and continuing at least weekly until 4 weeks of life or until completion of TPN, whichever comes later. Future studies should further evaluate possible etiologies of DH in this population.

Hirschsprung disease with Edward syndrome: A rare association: A case report.

INTRODUCTION AND IMPORTANCE: Edward's syndrome (ES) occurs as a result of trisomy of chromosome 18 and is associated with multisystem congenital anomalies. The association of ES with various gastrointestinal malformations but Hirschsprung disease (HD) is well documented. CASE PRESENTATION: A female infant on her 5th day of life presented with episodes of bilious vomiting along with abdominal distension and no passage of stool. The child had a small head and prominent occiput, low set abnormal ears, small jaw, upturned nose, widely spaced eyes, small neck with widely spaced nipples, clenched hands with overlapping fingers, flexed big toe, and prominent heels. CLINICAL DISCUSSION: Edward syndrome is associated with multisystem congenital abnormalities of which gastrointestinal abnormalities make up the most part. The condition can be identified by fetal ultrasound screening. Surgical correction of associated congenital anomalies at different times along with lifelong supportive management is important. CONCLUSIONS: Edward syndrome can present as Hirschsprung disease as a part of associated gastrointestinal Malformation. Often, early identification and termination of the pregnancy in antenatal life can reduce the suffering. Surgical correction of associated anomalies along with supportive care forms the cornerstone of management. However, the prognosis remains poor.

Surveillance guidelines for children with trisomy 18.

Trisomy 18 is the second most common aneuploidy syndromes in live born infants. It is associated with high mortality rates, estimated to be 75%-95% in the first year of life, as well as significant morbidity in survivors. The low survival is largely due to the high prevalence of severe congenital anomalies in infants with this diagnosis. However, interventions to repair or palliate those life-threatening anomalies are being performed at a higher rate for these infants, resulting in increased rates of survival beyond the first year of life. While it is well documented that trisomy 18 is associated with several cardiac malformations, these patients also have respiratory, neurological, neoplastic, genitourinary, abdominal, otolaryngologic, and orthopedic complications that can impact their quality of life. The goal of this review is to present a comprehensive description of complications in children with trisomy 18 to aid in the development of monitoring and treatment guidelines for the increasing number of providers who will be caring for these patients throughout their lives. Where the evidence is available, this review presents screening recommendations to allow for more rapid detection and documentation of these complications.

Advances in the proteomics of amniotic fluid to detect biomarkers for chromosomal abnormalities and fetomaternal complications during pregnancy.

INTRODUCTION: Amniotic fluid (AF) is a dynamic and complex mixture that reflects the physiological condition of developing fetus. In the last decade, proteomic analysis of AF for 16-18 weeks normal pregnancy has been done for the composition and functions of this fluid. Other body fluids such as urine, sweat, tears, etc. are being used for diagnosis of disease, but an insight into protein biomarkers of amniotic fluid can save the fetus and mother from future complications. Areas covered: We have covered the proteomics of amniotic fluid done since 2000, in order to strengthen the establishment of these techniques as a recognized diagnostic tool in the field. After classifying the diseases based on chromosomal aneuploidies, gestational changes, and inflammation caused during pregnancy; we have focused on amniotic fluid to detect various complications during and post pregnancy and its effect on the fetomaternal relationship. Expert comment: The main protein biomarkers responsible for various syndromes, diseases, and complications have been summarized. Major proteins identified for gestational conditions are IGFBP-1, fibrinogen, neutrophil defensins like calgranulins A and C, cathelicidin, APOA1, TRFE, etc. Validation of particular technique and establishing a single standardized biomarker for the diagnosis to avoid any overlapping for different diseases is required. After certain improvements, proteomics approach can be considered for diagnosis of diseases associated with fetal-maternal health.

Ocular manifestations in Edward's syndrome, a case report and literature review.

PURPOSE: To report a case with Edward's syndrome and ocular manifestations. METHODS: A three-year-old female visited our clinic. The diagnosis of Edward's Syndrome was made prior to the ophthalmic visit based on a karyotype study report. Complete ophthalmic evaluations were done for the patient. RESULTS: On the initial ophthalmic examination, bilateral ptosis, epicanthal folds, and 40 prism diopters alternate esotropia (ET) were seen. In the fundus examination, decreased red reflexes along with retinal folds, pigmentary retinopathy (patches of hyperpigmentation in the fovea and retinal periphery), and optic disc atrophy in both eyes were seen. CONCLUSION: Our case adds some evidence to the literature that ET may be one of the classic manifestations and anomalies in trisomy 18.

Anatomy of trisomy 18.

Trisomy 18 is the second most common aneuploidy after trisomy 21. Due to its multi-systemic defects, it has a poor prognosis with a 50% chance of survival beyond one week and a <10% chance of survival beyond one year of life. However, this prognosis has been challenged by the introduction of aggressive interventional therapies for patients born with trisomy 18. As a result, a review of the anatomy associated with this defect is imperative. While any of the systems can be affected by trisomy 18, the following areas are the most likely to be affected: craniofacial, musculoskeletal system, cardiac system, abdominal, and nervous system. More specifically, the following features are considered characteristic of trisomy 18: low-set ears, rocker bottom feet, clenched fists, and ventricular septal defect. Of particular interest is the associated cardiac defect, as surgical repairs of these defects have shown an improved survivability. In this article, the anatomical defects associated with each system are reviewed. Clin. Anat. 29:628-632, 2016. © 2016 Wiley Periodicals, Inc.

Síndrome de trisomía 18: reporte de un caso clínico / Trisomy 18 syndrome: a case report

Introducción El síndrome de trisomía 18 (T18) ocurre por la presencia de un cromosoma 18 extra completo en la mayoría de los casos. La prevalencia en recién nacidos oscila entre uno en 6.000 a uno en 8.000. Los afectados tienen una elevada mortalidad, solo el 4% supera el primer año de vida. Son pocos los casos reportados que superan los 5 años. Objetivo El objetivo de este artículo es reportar un caso de T18 de larga sobrevida con características en la cavidad oral no descritas en la literatura, y aportar información a médicos y pediatras sobre la etiología, el fenotipo, la sobrevida y el consejo genético. Reporte de caso Paciente de sexo femenino de 7 años con 2 cariotipos realizados en cultivo de linfocitos que mostraron 47,XX+18 en todas las metafases. Con talla y peso bajos, facies dismórficas, retardo severo del desarrollo psicomotor y cognitivo, imposibilidad para alimentarse, ausencia del lenguaje verbal, sordera neurosensorial, marcha atáxica, hipoplasia cerebelosa; genitales con labios mayores y menores hipoplásicos. En la cavidad oral paladar en forma de cúpula, macroglosia, no se observaron incisivos centrales superiores y primeros molares superiores e inferiores. En las radiografías se encuentran hallazgos de formación de las piezas dentales ausentes en la boca, concluyéndose erupción tardía. Conclusiones En los casos de T18 la mortalidad in útero y neonatal es alta, las características clínicas in útero y en recién nacidos han sido bien descritas. Dado que son pocos los casos que superan los 5 años el fenotipo aún está por establecerse. En la paciente aquí reportada se encontraron hallazgos en la cavidad oral no descritos en la literatura.

Introduction The trisomy 18 syndrome occurs due to the presence of an extra chromosome 18 in most cases. The prevalence in infants is estimated at 1:6000 to 1:8000. Those affected have a high mortality rate, only 4% may survive their first year of life. There are few reported cases exceeding five years of age. Objective The aim of this paper is to report a case of trisomy 18 of long survival with oral cavity features not described in the literature, and to provide information to physicians and paediatricians about aetiology, phenotype, survival and genetic counselling. Case report A 7 year-old female patient with 2 karyotypes performed by lymphocyte culture showing 47XX+18 in all metaphases. She presented with growth deficiency, dysmorphic facies, severe psychomotor retardation and cognitive disability, inability to feed, lack of verbal language, sensorineural hearing loss, ataxia, cerebellar hypoplasia, and genitals with hypoplastic labia majora and minora. In the oral cavity: dome shaped palate, macroglossia, absence of upper central incisors and first upper and lower molars in mouth. X-ray findings showed formation of missing teeth, with late eruption being concluded. Conclusions In cases of trisomy 18 syndrome there is an increased risk of neonatal and infant mortality. The clinical characteristics in utero and in neonates have been well described. Since few cases exceeding five years of age have been reported, the phenotype is yet to be established. In the case being reported we describe oral cavity findings not documented in the literature.

[Trisomy 18 syndrome: A case report]. / Síndrome de trisomía 18. Reporte de un caso clínico.

INTRODUCTION: The trisomy 18 syndrome occurs due to the presence of an extra chromosome 18 in most cases. The prevalence in infants is estimated at 1:6000 to 1:8000. Those affected have a high mortality rate, only 4% may survive their first year of life. There are few reported cases exceeding five years of age. OBJECTIVE: The aim of this paper is to report a case of trisomy 18 of long survival with oral cavity features not described in the literature, and to provide information to physicians and paediatricians about aetiology, phenotype, survival and genetic counselling. CASE REPORT: A 7 year-old female patient with 2 karyotypes performed by lymphocyte culture showing 47XX+18 in all metaphases. She presented with growth deficiency, dysmorphic facies, severe psychomotor retardation and cognitive disability, inability to feed, lack of verbal language, sensorineural hearing loss, ataxia, cerebellar hypoplasia, and genitals with hypoplastic labia majora and minora. In the oral cavity: dome shaped palate, macroglossia, absence of upper central incisors and first upper and lower molars in mouth. X-ray findings showed formation of missing teeth, with late eruption being concluded. CONCLUSIONS: In cases of trisomy 18 syndrome there is an increased risk of neonatal and infant mortality. The clinical characteristics in utero and in neonates have been well described. Since few cases exceeding five years of age have been reported, the phenotype is yet to be established. In the case being reported we describe oral cavity findings not documented in the literature.

Trisomy 18 syndrome: Towards a balanced approach.

Trisomy 18 is a relatively common autosomal trisomy syndrome. It is due to either full or partial presence of an extra copy of chromosome 18. Its prevalence correlates positively with advanced maternal age. Affected infants usually exhibit a variable pattern of anomalies including growth restriction, marked psychomotor and cognitive disability and an array of physical findings including characteristic craniofacial features, clenched fists with overriding fingers, small fingernails, underdeveloped thumbs, short sternum and heart and kidney anomalies. The majority of these infants die within the first year of life; only 5% to 10% of them survive longer. Their death is primarily due to cardio-respiratory failure. In this case report of trisomy 18 we tried to highlight the importance of antenatal diagnosis and to emphasize the need for proper counseling at different points of time starting from the moment the condition is suspected until the point when diagnosis is confirmed and thereafter.

Genetic Polymorphisms of STR Loci D18S53, D18S59 and D18S488 in Fetus in Tianjin / 天津医药

Objective To investigate the genetic polymorphisms of 3 short tandem repeat (STR) loci D18S53, D18S59 and D18S488 on chromosome 18 in fetus of Tianjin Han population, and to provide basic data in the use of 3 STR lo-ci in the prenatal diagnosis of Edward syndrome (ES). Methods A total of 64 villus samples and 374 amniotic fluid sam-ples were collected from gravida in Tianjin Han population. QF-PCR and ABI PRISM 377 sequence were used in this study. The frequencies of the genotypes were tested with H-W equilibrium. Genetic analysis was performed to conclude some data of population genetics such as the frequency of the alleles, the heterozygosity of observation (Ho), the polymorphism informa-tion content (PIC), the probability of discrimination power (DP), and the probability of exclusion (PE). Results The 15, 13 and 15 alleles of D18S53, D18S59 and D18S488 were observed respectively. The frequencies of the genotypes were in good agreement with H-W equilibrium. The Ho of 3 STR loci were 0.797, 0.847 and 0.792. The PIC was 0.81, 0.75 and 0.73. The DP was 0.944, 0.901 and 0.881. The PE was 0.593, 0.689 and 0.585. Conclusion D18S53, D18S59 and D18S488 STR lo-ci were the favorable genetic markers of chromosome 18, which can be used in prenatal genetic diagnosis of ES.

First Trimester Maternal Serum Screening Using Biochemical Markers PAPP-A and Free ß-hCG for Down Syndrome, Patau Syndrome and Edward Syndrome.

The first trimester screening programme offers a noninvasive option for the early detection of aneuploidy pregnancies. This screening is done by a combination of two biochemical markers i.e. serum free ß-human chorionic gonadotrophin (free ß-hCG) and pregnancy associated plasma protein A (PAPP-A), maternal age and fetal nuchal translucency (NT) thickness at 11 + 0-13 + 6 weeks of gestation. A beneficial consequence of screening is the early diagnosis or trisomies 21, 18 and 13. At 11 + 0-13 + 6 weeks, the relative prevalence of trisomies 18 and 13 to trisomy 21 are found to be one to three and one to seven, respectively. All three trisomies are associated with increased maternal age, increased fetal NT and decreased PAPP-A, but in trisomy 21 serum free ß-hCG is increased whereas in trisomies 18 and 13 free ß-hCG is decreased.

Rapid prenatal diagnosis of Down syndrome and Edward syndrome by fluorescence In situ hybridization:Clinical experience with 309 cases

PURPOSE: The purpose of this study was to evaluate the clinical utility of rapid detection of Down syndrome and Edward syndrome by Interphase Fluorescence in Situ Hybridization (FISH) analysis METHODS: A retrospective study in 309 cases of amniotic fluid samples, analysed by interphase FISH with DNA probes specific to chromosome 18 and 21, was performed. All FISH results were compared with conventional cytogenetic karyotypings. RESULTS: The results were considered as informative and they were obtained within 48 hrs. A case of Down syndrome and a case of Edward syndrome were diagnosed by FISH and confirmed by subsequent cytogenetic analysis. In 12 cases with normal FISH results, the cytogenetic analysis showed a case of partial trisomy 22, three cases of sex chromosomal aneuploidy, two cases of mosaicism, two cases of microdeletion, and four cases of structural rearrangement. CONCLUSION: FISH is a rapid and effective diagnostic method, which can be used as an adjunctive test to cytogenetic analysis, for prenatal identification of chromosome aneuploidies. For the more genome- wide screening with variety of probes, the technique of FISH is both expensive and labor-intensive.

Anesthetic Management of a Patient with Edward's Syndrome: A case report / 대한마취과학회지

Edward's syndrome (trisomy 18) is the second most common chromosomal anomaly next to Down syndrome. The patients are dysmorphic, have multiple organ malformation which is made to die with 90% by 12 months. Information in the literature about anesthetic management in trisomy 18 is rare. We report the case of a 7 months old male with trisomy 18 who underwent inguinal hernioplaty and orchiopexy with general anesthesia.

A Case of Edward Syndrome with Choroid Plexus Cyst / 대한산부인과학회잡지

Trisomy 18 is the second most common chromosomal anomaly which reach to live birth next to Down syndrome. Several methods were proposed to screen patients on the risk of Edward syndrome like maternal serum levels of total human chorionic gonadotropin (hCG), alpha-fetoprotein (AFP) and unconjugated estriol or free beta hCG with AFP, but the serum screening has only 67% detection rate with a 7.2% of false positive rate. Therefore, in order to overcome the limitations which the serum markers have, detailed ultrasound examination is also necessary and sensitivity of 80% was reported. We report a case of Trisomy 18 fetus in which choroid plexus cyst was the only abnormal sonographic finding.

A case of Full Term Delivery of a Edward Syndrome Associated with Dandy-Walker Syndrome subsequent to Prenatal Diagnosis / 대한산부인과학회잡지

Dandy-Walker syndrome indicates the association of cystic dilatation of fourth ventricle, dysgenesis of the cerebellar vermis and a high position of the tentorium. Dandy-Walker syndrome has an estimated prevalence of about 1 in 30,000 births and is found in 4% to 12% of all cases of infantile hydrocephalus. And trisomy 18 was present in 4.8% of the Dandy-Walker syndrome. Trisomy 18 is a chromosomal aneuploid, which results in multiple severe structural abnormalities that mostly involve the heart, extremities, face, and brain. We experienced a case of Edward syndrome associated with Dandy-Walker syndrome. She did not want to terminate her pregnancy. So, we reviewed a Edward syndrome with Dandy-Walker syndrome and presented the final result in full term delivery.

A case of Edward syndrome with radius aplasia / 대한산부인과학회잡지

Trisomy 18 is the second most common chromosomal anomaly that reach to live birth after Down syndrome. Several methods were proposed to screen patients on the risk of Edward syndrome like maternal serum levels using total human chorionic gonadotropin (hCG), alpha-fetoprotein (AFP) and unconjugated estriol (uE3), or free beta hCG with AFP, but the serum screening has only 50-60% detection rate with a 1-2% of false positive rate. So to cover the limitations that serum marker has, detailed ultrasound examination is also necessary and sensitivities of 65-70% were reported. We report a case of trisomy 18 fetus in which second trimester triple markers of maternal serum was normal, but by detailed ultrasound examination, unilateral radius aplasia was diagnosed cytogenetic study confirmed the fetus as trisomy 18.

A Case of Edward Syndrome / 대한산부인과학회잡지

Trisomy 18, called Edward syndrome, occurs in about 3500-8000 births. It is much more common at conception, with about 95% of cases resulting in spontaneous abortion or stillbirth. Postnatal survival is poor, with the majority of patients dying in early infancy. Characteristic findings include cardiac malformations, mental retardation, growth retardation, a prominent occiput, micrognathia, clenched hands, and rocker-bottom feet, omphalocele. The prenatal sonographic findings of our case include delayed growth, omphalocele, wrist joint fixation, choroid plexus cyst, hydramnios and postnatal gross findings include growth retardation, omphalocele, wirst joint fixation, absence of radius, syndactyly, focal absence of phalanges and flexion deformities of fingers and toes. We report a case of prenatally diagnosed Edward syndrome, which is confirmed by chromosome analysis, with brief review of related literatures.

Review of Prenatal Sonographic findings in Edward syndrome / 대한산부인과학회잡지

PURPOSE: The purpose is to aid in the diagnosis and obstetric management by analysing the ultrasonographic findings of prenatally diagnosed Edward syndrome. METHOD: The study population consisted of 15 cases prenatally diagnosed Edward syndrome from January 1993 to January 1999. The medical charts and ultrasonographic findings were reviewed retrospectively, and especially the ultrasonographic findings before prenatal genetic diagnosis were anlyzed. RESULTS: All of the 15 cases reviewed showed at least one ultrasonographic finding suggesting Edward syndrome. In the first trimester, 2 cases revealed cystic hygroma and increased nuchal translucency, and after the second trimester, major structural anomalies including congenital heart anomalies and minor ultrasonographic findings such as choroid plexus cyst were noted. All of cases after 21 weeks of gestation showed congenital heart anomaly, and as the pregnancy progressed there was an increased tendency of intrauterine growth restriction and polyhydramnios. CONCLUSION: Prenatal ultrasonography in the screening process of Edward syndrome can be placed as a very informative method, as all of the Edward syndrome cases revealed at least one abnormal ultrasonographic findings. As congenital heart anomalies were found in all of the cases after 21 weeks of gestation, fetal echocardiography should be considered in evaluating suspected cases of Edward syndrome.