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.

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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.

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