Trisomy 18

Epidemiology and Etiology:

• Nondisjunction – most commonly maternal MII
• Risk factors:
• Advanced maternal age
• 1:6000-8000 births
• M:F = 1:3-4

Common sites:

Gross features:

• Hydrops fetalis maybe
• multiple multisystem abnormalities
• hypotonicity neonatally followed by hypertonicity
• craniofacial dysmorphism
• prominent occiput
• narrow bifrontal diameter
• short palpebral fissures
• small mouth
• narrow palate
• low-set malformed ears
• micrognathia
• neural tube defects
• hydrocephaly
• clenched hands with a tendency for the 2^nd finger to overlap the 3^rd, and the 5^th finger to overlap the 4^th.
• Short dorsiflexed hallux
• Hypoplastic nails
• Rocker bottom feet
• Short sternum
• Abdominal wall defects
• Hernias
• omphalocele
• congenital diaphragmatic hernia (CDH)
• Single umbilical artery
• Renal abnormalities
• Small pelvis
• Cryptorchidism
• Hirsuitism
• Cardiac anomalies
• VSD
• ASD
• PDA
• Mosaic:
• Milder phenotype in general

Histologic features:

Immunophenotype:

Marker:

Sensitivity:

Specificity:

Molecular features:

• trisomy 18
• critical regions:
• 18q12.1-q21.2
• 18q22.3-qter
• 18q12.3-q21.1 alone is associated with severe mental retardation
• proximal to 18q12 is non-contributory to syndrome

Other features:

• hydrops fetalis maybe
• clinical features:
• severe mental retardation
• ultrasound (2^nd trimester):
• Choroid plexus cyst
• Cardiac defects
• Cystic hygroma
• Omphalocele
• Diaphragmatic hernia
• Neural tube defect
• Rockerbottom feet
• Clubfeet
• Clenched hands
• Radial ray anomalies
• Strawberry shape skull
• IUGR
• Polyhydramnios
• renal abnormalities
• prognosis
• median 5d survival
• <10% survival beyond 1y
• rare > 10y
• recurrence:
• <1% for subsequent pregnancy
• not well studied

References:

• Gersen SL & Keagle MB, eds. The Principles of Clinical Cytogenetics (2005)
• Evans MI, ed. Prenatal Diagnosis (2006)