CHROMOSOMES




1.1 TRIPLOIDY



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EPIDEMIOLOGY/GENETICS



Definition Rare, lethal chromosomal abnormality. An entire extra haploid set of chromosomes results in 69 chromosomes instead of the usual 46.



Epidemiology Of human conceptions, 1% to 2% are triploid, but most end in spontaneous abortion. Accounts for 20% of chromosomally abnormal spontaneous abortions. Very rare at birth, occurring in 1 in 10,000 live births.



Embryology A complete extra set of chromosomes results in 69 XXX (digynic) or XXY (diandric). Sixty percent result from fertilization with two sperm; 40% result from fertilization of a diploid egg. However, more recent prospective information, at the time of first-trimester screening, suggests that digynic triploidy may be more common than diandric. Central nervous system malformations include hydrocephalus, holoprosencephaly, and neural tube defects. Hypertelorism, cleft lip/cleft palate, syndactyly of the third and fourth fingers, and congenital heart defects are typical features.



Inheritance Patterns Sporadic



Teratogens None



Screening Serum levels of human chorionic gonadotropin and inhibin A may be extremely high in triploidy with dispermy as the cause. Very low levels of α-fetoprotein, estriol, inhibin A, and human chorionic gonadotropin (hCG) are seen in pregnancies in which fertilization of a diploid egg occurs. In the first trimester, screening, using nuchal translucency and serum markers will detect approximately 85% of fetuses with triploidy. Diandric triploids have an increased nuchal translucency, elevated hCG, and normal, or low, pregnancy-associated plasma protein A (PAPP-A). Digynic triploidy has a normal nuchal translucency, very low hCG, and very low PAPP-A. Diandric triploidy will generally look like an increased risk for trisomy 21, and digynic will generally look like a high risk for trisomy 18.



Prognosis Lethal antenatally or in the newborn period. Rare mosaic cases survive with moderate-to-severe mental retardation.



SONOGRAPHY



Findings: Sonographic findings vary with the source of the extra chromosome.



FREQUENT FINDINGS




  • First-trimester thickened nuchal translucency



  • Intrauterine growth restriction




    • Asymmetric growth restriction with large fetal head is associated with digynic triploidy



    • There is early-onset symmetrical growth restriction.



    • Some fetuses with diandric triploidy have grown normally.



  • Ventriculomegaly



  • Holoprosencephaly



  • Micrognathia



  • Low-set ears



  • Single umbilical artery



  • Syndactyly of third and fourth fingers



  • Clubfeet



  • Oligohydramnios



  • Enlarged placenta with multiple cystic spaces; similar to a partial mole (diandric, XXY)



  • Small placenta (digynic, XXX)



  • Bilateral theca lutein cysts




LESS FREQUENT




  • Neural tube defects



  • Dandy-Walker malformation



  • Agenesis of the corpus callosum



  • Microphthalmia



  • Hypertelorism



  • Cystic hygroma



  • Coarctation of aorta



  • Hypoplastic left ventricle



  • Omphalocele



  • Pyelocaliectasis



  • Ambiguous genitalia



  • Nonimmune hydrops




    • Pleural effusion



    • Pericardial effusion



    • Ascites



    • Anasarca




PREGNANCY MANAGEMENT



Investigations and Consultations Traditional karyotyping with, or without, fluorescent in situ hybridization (FISH) analysis via amniocentesis or chorionic villi sampling (CVS) establishes the diagnosis. Once a cytogenetic diagnosis has been established, no further investigations or consultations are necessary. For patients in whom the diagnosis is made beyond the point of legal pregnancy termination or in those who decide to continue the pregnancy, a neonatologist should consult with the family about appropriate perinatal and neonatal management. The family should be offered supportive psychological care throughout the pregnancy.



Monitoring If pregnancy termination is not an option, monitor for preeclampsia or hyperthyroidism. Either of these complications is an indication for treatment, including immediate delivery without regard to gestational age.



Pregnancy Course Molar changes in the placenta predispose to hyperemesis gravidarum, early preeclampsia, theca lutein cysts, and, on occasion, hyperthyroidism. Prenatal care should be modified such that only interventions for maternal health, rather than fetal health, are offered. Intrauterine growth restriction is common, and aggressive management with fetal monitoring is inappropriate.



Pregnancy Termination Issues Use of suction dilatation and evacuation, or any other method of pregnancy termination, is appropriate once a cytogenetic diagnosis has been established.



Delivery Fetal monitoring and cesarean section are both contraindicated for the pregnancy complicated by a triploidy.



NEONATOLOGY



Resuscitation Contraindicated if the diagnosis is definite because of the established lethal prognosis.



Transport Indicated only if diagnostic confirmation, counseling, and long-term care planning are not available locally.



Testing and Confirmation A peripheral blood chromosome study can confirm the chromosome abnormality.



Nursery Management Provision of basic supportive care—warmth, hygiene, nourishment, and comfort only— until prognosis for protracted survival is defined and long- term care decisions can be addressed with the family.



SUGGESTED READINGS





Daniel  A, Wu  Z, Bennetts  B,  et al: Karyotype, phenotype, and parental origin in 19 cases of triploidy. Prenat Diagn 2001; 21:1034–1048.  [PubMed: 11746161]


Edwards  MT, Smith  WL, Hanson  J, Abu Yousef  M: Prenatal sonographic diagnosis of triploidy. J Ultrasound Med 1986; 5:279–281.  [PubMed: 3517376]


Engelbrechtsen  L, Brondum-Nielsen  K, Ekelund  C,  et al: Detection of triploidy at 11-14 weeks’ gestation: a cohort study of 198,000 pregnant women. Ultrasound Obstet Gynecol 2013; 42:530–535.  [PubMed: 23494847]


Jauniaux  E, Brown  R, Rodeck  C, Nicolaides  KH: Prenatal diagnosis of triploidy during the second trimester of pregnancy. Obstet Gynecol 1996; 88:983–989.  [PubMed: 8942839]


Jauniaux  E, Brown  R, Snijders  RJM,  et al: Early prenatal diagnosis of triploidy. Am J Obstet Gynecol 1997; 176;550–554.  [PubMed: 9077605]


Joergensen  MW, Niwmann  I, Rasmussen  AA,  et al: Triploid pregnancies: genetic and clinical features of 158 cases. Am J Obstet Gynecol 2014; 211:370.e1–19.


Jones  KL, Jones  MC, del Campo  M: Smith’s Recognizable Patterns of Human Malformations. 7th ed. Philadelphia: Elsevier; 2013.


Kagan  KO, Anderson  JM, Anwandter  G,  et al: Screening for triploidy by the risk algorithms for trisomies 21, 18 and 13 at 11 weeks to 13 weeks and 6 days of gestation. Prenat Diagn 2008; 28:1209–1213.  [PubMed: 19039823]


Lockwood  C, Scioscia  A, Stiller  R, Hobbins  J: Sonographic features of the triploid fetus. Am J Obstet Gynecol 1987; 157:285–287.  [PubMed: 3303932]


McFadden  DE, Pantzar  JT: Placental pathology of triploidy. Hum Pathol 1996; 27:1018–1020.  [PubMed: 8892584]


Mittal  TK, Vujanic  GM, Morrissey  BM, Jones  A: Triploidy: antenatal sonographic features with post-mortem correlation. Prenat Diagn 1998; 18:1253–1262.  [PubMed: 9885016]


Pircon  RA, Porto  M, Towers  CV,  et al: Ultrasound findings in pregnancies complicated by fetal triploidy. J Ultrasound Med 1989; 8:507–511.  [PubMed: 2674473]




FIGURE 1.1A


Triploidy-Thickened (4 mm) nuchal translucency.






FIGURE 1.1B


Digynic Triploidy-1st trimester disproportion between head and abdomen.






FIGURE 1.1C


Digynic Triploidy-2nd trimester disproportion between head and abdomen.






FIGURE 1.1D


Diandric Triploidy-cystic placenta (+ … +).






FIGURE 1.1E


Triploidy with alobar holoprosencephaly






FIGURE 1.1F


Triploidy with Dandy-Walker malformation (arrow).






1.2 TRISOMY 13



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EPIDEMIOLOGY/GENETICS



Definition Because of its higher intrauterine mortality, trisomy 13 is the least common of the major autosomal trisomies. Fetuses with trisomy 13 tend to have more craniofacial (median cleft, micro- or anophthalmia) and brain (holoprosencephaly) abnormalities. While trisomy 13 is frequently referred to as lethal, this is not always the case. The median survival is 7 days, and 90% of trisomy 13 newborns die by 1 year of age.



Epidemiology One in 5000 to 10,000 births



Embryology The phenotype is due to full trisomy 13. Increased maternal age has been documented in this disorder. Rare mosaic partial trisomy 13 syndromes (with varying phenotypes) and translocation patients have been reported. Microcephaly, holoprosencephaly, microphthalmia, polydactyly, and facial clefts are found in more than 50% of patients. Eighty percent of patients have congenital heart defects, with atrial septal defects (ASDs) and ventricular septal defects (VSDs) the most common. However, many patients have complex heart lesions. Other distinctive abnormalities include polycystic kidneys (30% of patients) and omphalocele (<50% of patients).



Inheritance Patterns Most cases are sporadic, with approximately a 1-in-100 risk of recurrence in future pregnancies. Rare familial translocations have a higher recurrence risk, depending on the specific translocation.



Teratogens None



Screening Second-trimester maternal serum biochemical marker screening is not helpful in detecting trisomy 13 fetuses. Some cases are diagnosed by first-trimester screening because of increased nuchal translucency and fetal malformations. Noninvasive prenatal testing (NIPT) will detect 90% to 95% of cases.



Prognosis This condition is lethal or has a very poor prognosis in all cases. Live births occur in 40% to 60%, but 90% die in the first year. All survivors with full trisomy 13 have profound mental retardation. In infancy, severe failure to thrive, feeding difficulties, seizures, apneic attacks, and visual and hearing deficits occur in the majority of infants, secondary to the orofacial and central nervous system defects.



SONOGRAPHY



Findings: The number and severity of congenital anomalies associated with trisomy 13 are highly variable.



FREQUENT FINDINGS




  • First-trimester thickened nuchal translucency



  • Holoprosencephaly




    • The presence of a cavum septum pellucidum excludes a significant forebrain abnormality.



  • Microcephaly



  • Central cleft lip and palate



  • Enlarged cisterna magna



  • Hypotelorism



  • Low-set ears



  • Polydactyly



  • Clubfeet



  • Congenital heart defect




    • Ventricular septal defect



    • Atrial septal defect



    • Hypoplastic left ventricle



    • Aortic stenosis



    • Pulmonary stenosis




LESS FREQUENT




  • First-trimester megacystis



  • Agenesis of the corpus callosum



  • Cerebellar hypoplasia



  • Basal ganglia calcifications



  • Single orbit with 2 globes, cyclops



  • Microphthalmia



  • Single nostril



  • Proboscis



  • Rocker-bottom feet



  • Clubhands



  • Overlapping fingers



  • Echogenic enlarged kidneys containing small cysts



  • Omphalocele



  • Neural tube defect




PREGNANCY MANAGEMENT



Investigations and Consultations Traditional karyotyping with, or without, FISH analysis via amniocentesis or CVS establishes the diagnosis. A positive result from maternal blood of cell-free circulating fetal DNA is considered a screening test and is not sufficient to establish the diagnosis. Once a cytogenetic diagnosis has been established, no further investigations or consultations are necessary. For patients in whom the diagnosis is made beyond the point of legal pregnancy termination or in those who decide to continue the pregnancy, a neonatologist should consult with the family about appropriate perinatal and neonatal management. The family should be offered supportive psychological care throughout the pregnancy.



Monitoring Only routine prenatal care should be performed. Monitoring for preeclampsia is appropriate, as it is more common in pregnancies complicated by trisomy 13. This complication is an indication for treatment, including immediate delivery, without regard to gestational age.



Pregnancy Course Prenatal care should be modified such that only interventions for maternal health, rather than fetal health, are offered. Intrauterine growth restriction is common, and aggressive management with fetal monitoring is inappropriate.



Pregnancy Termination Use of suction dilatation and evacuation, or any other method of pregnancy termination, is appropriate once a cytogenetic diagnosis has been established.



Delivery Electronic fetal monitoring and cesarean section should be avoided unless requested by the family after a thorough discussion of the prognosis for infants with trisomy 13.



NEONATOLOGY



Resuscitation A decision about whether to give life support should be made prior to delivery, once the diagnosis is established. If the diagnosis is unknown prior to birth, providing life support is appropriate until a diagnosis can be established.



Transport Indicated only if diagnostic confirmation, counseling, and long-term care planning are not available locally.



Testing and Confirmation Obtain peripheral blood, or cord blood, for chromosome analysis to confirm the diagnosis.



Nursery Management Full life support is appropriate until the diagnosis is confirmed and the family has time for weighing options for duration and intensity of support. Care requirements will be contingent on associated organ involvement and the long-term goals of the family.



SUGGESTED READINGS





Chen  C-P, Chien  S-C: Prenatal sonographic features of trisomy 13. J Med Ultrasound 2007; 15:58–66.


Hosseinzadeh  K, Luo  J, Borhani  A, Hill  L: Non-visualization of cavum septi pellucidi: implication in prenatal diagnosis? Insights Imaging 2013; 4:357–367.  [PubMed: 23584847]


Janvier  A, Watkins  A. Medical interventions for children with trisomy 13 and trisomy 18: what is the value of a short disabled life? Acta Paediatr 2013;12:1112–1117.


Jones  KL, Jones  MC, del Campo  M. Smith’s Recognizable Patterns of Human Malformations. 7th ed. Philadelphia: Elsevier; 2013.


Liao  AW, Sebire  NJ, Beerts  L,  et al: Megacystis at 10-14 weeks of gestation: chromosomal defects and outcome according to bladder length. Ultrasound Obstet Gynecol 2003; 26:338–341.


Loureiro  T, Ferreira  AFA, Ushakov  F,  et al: Dilated fourth ventricle in fetuses with trisomy 18, trisomy 13, and triploidy at 11-13 weeks’ gestation. Fetal Diagn Ther 2012; 32:186–189.  [PubMed: 22846426]


Matias  A, Montenegro  N, Areias  JC, Brandao  O: Anomalous fetal venous return associated with major chromosomopathies in the late first trimester of pregnancy. Ultrasound Obstet Gynecol 1998; 11:209–213.  [PubMed: 9589146]


Merritt  TA, Catlin  A, Wool  C,  et al: trisomy 18 and trisomy 13. Neoreviews 2012; 13:e40–e48.


Quezada  MS, Gil  MM, Francisco  C,  et al: Screening for trisomies 21, 18, and 13 by cell-free DNA analysis of maternal blood at 10-11 weeks’ gestation and the combined test at 11-13 weeks. Ultrasound Obstet Gynecol 2014; 20:1–6.


Papageroghiou  AT, Avgidou  K, Spencer  K,  et al: Sonographic screening for trisomy 13 at 11 to 13 (+6) weeks of gestation. Am J Obstet Gynecol 2006; 194:397–401.  [PubMed: 16458636]


Springett  AL, Morris  JK: Antenatal detection of Edwards (trisomy 18) and Patau (trisomy 13) syndrome: England and Wales 2005-2012. J Med Screen 2014; 21(3): 113–119.  [PubMed: 24993362]


Watson  WJ, Miller  RC, Wax  JR,  et al: Sonographic detection of trisomy 13 in the first and second trimesters of pregnancy. J Ultrasound Med 2007; 26:12069–1214.




FIGURE 1.2A


Trisomy 13 with 1st trimester megacystis (+ … +).






FIGURE 1.2B


Normal cavum septum pellucidum (arrow).


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Jan 12, 2019 | Posted by in GYNECOLOGY | Comments Off on CHROMOSOMES
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