CHAPTER 1: CHROMOSOMES

1.1 TRIPLOIDY

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 ...