Edward Syndrome or Trisomy 18 - Essay Example

Edward Syndrome or Trisomy 18 Definition and prevalence Trisomy 18, also known as Edward syndrome, is the most common autosomal trisomy after trisomy 21 (Chen, Emedicine). The syndrome was first described by Edwards et al in 1960 and hence the name (Chen, Emedicine). The condition affects all the organs of the body and is characterized by severe mental and physical growth retardation, microcephaly, microstomia, micrognathia and microphthalmia, malformation of the ears, clenched fingers and many other congenital problems. The prevalence of this condition in the United States is about 1 in 6,000- 8,000 live births. The incidence of the condition during first trimester scanning is 1 in 400 (Chen, Emedicine). There is a strong female predominance with more than 80 percent of the detected cases being females. The condition does not have any racial predilection(Chen, Emedicine). Morbidity and mortality 95 percent of pregnancies with trisomy 18 embryos spontaneously abort. Of the remaining which are born, only 5-10 percent survive beyond the first year of life. Thus, the mortality rate of this condition is very high. The mortality rate is because of the severely malformed organs like the heart, kidney and the brain, feeding problems, high rates of infection and breathing difficulties. The longest survival reported for this condition so far is 27 years (Chen, Emedicine). Clinical presentation The condition is detectable in the prenatal period. Some of the features which point to the possibility of trisomy 18 are maternal polyhydramnios or oligohydramnios, very small placenta, single umbilical artery, intrauterine growth retardation, fetal distress, defective fetal reflexes and decreased fetal activity. In the postnatal period, the clinical condition is obvious because of the array of clinical features. The new born usually has generalized hypotonia, apnea, jitteriness and seizures. The child will have marked failure to thrive, recurrent apnoiec episodes and poor feeding (Chen, Emedicine). On examination several organ defects will be obvious. The child may have defects of the skull manifesting as microcephaly, wide fontanellaes, prominent occiput, elongated skull or even narrow bifrontal diameter. Facial deformities include microphthalmia, micrognathia, microstomia, short palpebral fissures, epicanthal folds, choanal atresia, periauricular tags, and narrow palatal arch. Severe skeletal deformities exist including growth retardation, radial hypoplasia, clenched hands, syndactyly, rocker bottom feet, narrow pelvis, talipes equinovarus, etc. Typical of the clenched fingers include "overlapping digits, with the second and fifth fingers overlapping the third and fourth fingers, respectively." Cardiac defects are very common and present in more than 90 percent of the infants. Common cardiac defects include polyvalvular disease, septal defects, hypoplastic left heart syndrome, tetralogy of Fallot and transposition of great arteries. In the kidneys, multiple cysts can be seen. other genitourinary problems include hydroureters, hydronephrosis, renal agenesis, cryptorchidism, hypoplasia of female organs, etc. Endocrine problems like hypothroidism and hypoadrenalism may occur. Gastrointestinal anomalies are predominant and contribute to feeding difficulties, reflux and poor weight gain. The complications include malrotation of intestine, omphalocele, Meckel diverticulum, esophageal atresia, tracheo-esophageal fistula, accessory spleens, absent gall bladder, absent appendix, diaphragmatic eventration, imperforate anus, malpositioned sinus, diagphragmatic hernia, pilonidal sinus, diastasis recti and common mesentery. In translocations and mosaics, the clinical presentation is less severe and the survival chances are usually much longer (Chen, Emedicine). Etiology More than 95 percent of Edwards syndrome cases are due to Full trisomy 18. The remaining are due to translocations and mosaicism. The incident rate of the condition increases with maternal age. In more than 90 percent of the cases, the origin of the extra chromosome is maternal and due to errors in meiosis-2. However, mosaic trisomy occurs due to nondisjunction of maternal meiosis and such cases account for about 5 percent of cases of trisomy 18. The clinical phenotype in these cases is dependent on the level of mosaicism (Chen, Emedicine). Diagnosis During the first week of life, hematological studies are important because of the increased incidence of thrombocytopenia, neutropenia and abnormal erythrocytes in patients with Edward syndrome. Cytogenetic studies reveal whether the chromosomal anomaly is complete trisomy 18 or whether it is a translocation type or mosaic type. Imaging studies are very critical to diagnose congenital anomalies. Echocardiography detects cardiac anomalies. The most common cardiac anomaly is the ventricular septal defect, followed by patent ductus arteriosus (Chen, Emedicine). To ascertain gastrointestinal anomalies, barium swallow must be done. Cranial ultrasonography is useful to reveal brain anomalies. The most common anomaly in the brain is cerebellar hypoplasia. This is followed by edema of the brain, cisterna magna enlargement and cysts of the choroid plexus. Other neurological malformations include holoprosencephaly, defective falx cerebri, migration defect, myelomeningocele, arachnoid cyst, frontal lobe defect and aplasia of corpus callosum. Genitourinary anomalies also have to be delineated using ultrasonography. To study skeletal problems, skeletal radiography is useful and helps to discern abnormalities like phocomelia, talipes equinovarus, hemivertebrae, short neck, dislocated hip, rib anomalies and absent radius (Chen, Emedicine). Abnormal lobation of lung and ppulmonary hypoplasia may be present. 3- dimensional or 4-dimensional ultrasonography are better to evaluate anomalies, especially for anomalies of face and extremities (Chen, Emedicine). Management The main treatment for trisomy 18 is supportive medical care. Infections must be treated appropriately with antibiotics. Feeding problems must be managed with gastrostomy and nasogastric supplementation. Orthopedic management of problems like scoliosis may be needed. For cardiac anomalies, medical management of cardiac problems is essential. In view of the poor prognosis associated with the disease, surgical repair of cardiac anomalies is a controversial topic. Genetic counselling, psychosocial management and other services must be provided for the parents (Chen, Emedicine). Prenatal diagnosis Recent surge in the diagnostic research has contributed to the ability to screen and diagnose trisomy 18 in the prenatal period itself. The screening tests which hint at the presence of trisomy 18 in the fetal ultrasound and triple screen or maternal serum screening. In triple test, alpha-feto protein, human chorionic gonadotrophin and estriol levels are checked. The test is performed between 15- 17 weeks of gestation. This test only detects the risk of trimosies (American Pregnancy Association). It is performed in those with a positive family of birth defects, advanced maternal age of beyond 35 years, use of drugs and medications which are contraindicated in pregnancy, presence of gestational diabetes mellitus, history of viral infection during pregnancy and exposure to radiation during pregnancy (Chen, Emedicine). Low levels of alpha-fetoprotein, estriol and human chorionic gonadotrophin are indicative of chromosome abnormalities and necessitate further investigations in terms of ultrasound evaluation, chorionic villous sampling and amniocentesis (American Pregnancy Association). Level-2 ultrasound or the targetted ultrasound is the most effective method of evaluation in trisomy-18. Though an exact diagnosis of trisomy 18 cannot be made by prenatal ultrasonography, several abnormal sonologic findings can be detected in the fetus as early as the first trimester (Shields, 327). The main markers include Dandy-Walker malformation and microcephaly (Hagen- Ansert, 119) In the former, there is enlargement of the posterior fossa associated with hypoplasia of the cerebellum. In a study by Sepulveda et al (p.256), the researchers reviewed the sonologic findings of trisomy 18 cases during the first trimester. In their study, the authors found that all most all the fetuses with trisomy 18 demonstrated more than one sonologic abnormality. The most common abnormality was nuchal translucency thickness. The next common abnormality detected was hypoplastic or absent nasal bone (Sepulveda, 258). Other structural anomalies detected in the sonology are omphalocele, megacystis, abnormal posturing of hands and abnormal four chamber view of the heart. In some cases, bradycardia and fetal growth restriction were also seen. 3- dimensional or 4-dimensional ultrasonography are better to evaluate anomalies, especially for anomalies of face and extremities (Chen, Emedicine). When more than one defect is seen in the ultrasound, further evaluation in terms of chorionic villous sampling or CVS and amniocentesis is indicated. CVS is performed between 10- 12 weeks of gestation. Beyond that period amniocentesis is performed. The risk of fetal loss with CVS is 0.5- 1 percent. It is 96- 98 percent accurate. Amniocentesis is performed between 14- 6 weeks of gestation. It is 99.5 percent accurate. It has a small risk of abortion, bout 1 in 200 cases (Chen, Emedicine). Genetic counseling must be provided for those with established diagnosis of trisomy 18. The parents will be counseled to terminate the pregnancy. Differential diagnosis The main differential diagnoses include other malformation syndromes like trisomy 21, pseudo-trisomy syndrome, monosomies, other trisomies, fetal akinesia sequence and mental retardation syndromes (Chen, Emedicine). Complications Some of the common complications of this condition are infection, scoliosis, feeding problems, congestive heart failure and Wilms tumor. Congestive heart failure is one of the common causes of death in these children (Chen, Emedicine). Prognosis Survival beyond first year of life is guarded and associated with severe complications. While new born babies have 40 percent chances of surviving to one month of age, infants have only 5 percent chances of surviving to beyond one year of age. Further from there, there is only one percent chance of surviving to 10 years of age. Prolonged survival may be seen in mosaic and translocation cases (Chen, Emedicine). Medicolegal issues Medicolegal problems arise when the sonologist fails to identify defects which point towards Edwards syndrome and make appropriate referrals. Other issues include failure to ask for chromosomal analysis on clinical diagnosis of Edward syndrome, failure to offer prenatal evaluation to pregnant women and failure to offer evaluation once a child with trisomy 18 or other congenital defect is born in the family (Chen, Emedicine). Works Cited Page American Pregnancy Association. “Prenatal testing.” 2003. 27th March, 2010 http://www.americanpregnancy.org/prenataltesting/ Callen, Peter. “Ultrasonography in Obstetrics and Gynecology.” 5th Edition. Mosby and Saunders. Chen, Harold. “Trisomy 18.” Emedicine from WebMD. July 10, 2009. 27th March, 2010 Hagen- Ansert, Sandra. Text Book of Diagnostic Ultrasonography. 6th Edition. 2010 Elsevier Incorporation Sepulveda, W, Wong, AE, Dezerega, V. “First-trimester sonographic findings in trisomy 18: a review of 53 cases.” Prenatal Diagnosis, 30(3), March 2010: 256- 259. Shields, Laurence, Carpenter, Leslie, Smith, Karin, Nghiem, Hanh. “Ultrasonographic Diagnosis of Trisomy 18: Is it practical in the early second trimester.” J Ultrasound Med., 17, 1998, 327- 331. Read More