Trisomy 18: Difference between revisions

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===Reviews===
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Revision as of 01:26, 23 January 2013

Chromosome- trisomy 18.jpg

Introduction

Karyotype Trisomy 18 male

(Edwards Syndrome, 18T) An aneuploidy, first recognized as a specific clinical entity by the discovery of an extra chromosome 18 in babies with a particular pattern of malformation by independent groups.[1] [2] [3]


Both trisomy 13 and trisomy 18 are generally considered fatal anomalies, with a majority of infants dying in the first year after birth.[4]


Links: Human Abnormal Development | Trisomy 21 | Trisomy 18 | Trisomy 13 |

Some Recent Findings

  • Recent Trisomy 18 Review. [5] "The trisomy 18 syndrome, also known as Edwards syndrome, is a common chromosomal disorder due to the presence of an extra chromosome 18, either full, mosaic trisomy, or partial trisomy 18q. The condition is the second most common autosomal trisomy syndrome after trisomy 21. The live born prevalence is estimated as 1/6,000-1/8,000, but the overall prevalence is higher (1/2500-1/2600) due to the high frequency of fetal loss and pregnancy termination after prenatal diagnosis. The prevalence of trisomy 18 rises with the increasing maternal age. The recurrence risk for a family with a child with full trisomy 18 is about 1%. Currently most cases of trisomy 18 are prenatally diagnosed, based on screening by maternal age, maternal serum marker screening, or detection of sonographic abnormalities (e.g., increased nuchal translucency thickness, growth retardation, choroid plexus cyst, overlapping of fingers, and congenital heart defects). "
  • Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies[6]

Features

Frequency Organ/System Prevalent type of malformation
Common (>75%) heart septal defects, patent ductus arteriosus, and polyvalvular disease
Frequent (25-75%) genitourinary horseshoe kidney
Less frequent (5-25%) gastrointestinal

central nervous system

craniofacial

eye

limb

omphalocele, esophageal atresia with tracheo-esophageal fistula, pyloric stenosis, Meckel diverticulum

cerebellar hypoplasia, agenesis of corpus callosum, polymicrogyria, spina bifida

orofacial clefts

microphthalmia, coloboma, cataract, corneal opacities

radial aplasia/hypoplasia

Table modified from[5]

Pedbase Entry

Definition

A chromosomal disorder resulting in a syndrome characterized by specific (small) dysmorphic features and organ malformations.

Epidemiology

incidence: 1/8000 live births most die in embryonic or fetal life 2nd most common autosomal aberration 2nd most common multiple malformation syndrome age of onset: newborn risk factors: advanced maternal age F > M (4:1)

History

1960 first recognized as a specific clinical entity by the discovery of an extra chromosome 18 in babies with a particular pattern of malformation by three independent groups (Edwards et al., Patau et al., Smith et al.)

Pathogenesis - Genetics

Trisomy 18

90% of cases due to meiotic nondisjunction less than 1% recurrence rate

Mosaicism

10% of cases due to postzygotic (postfertilization) mitotic nondisjunction leads to the partial clinical expression of Trisomy 18 with a longer survival

Translocations

very rare give rise to partial trisomy 18 syndromes short arm: causes non-specific clinical features with mild or no mental deficiency long arm: entire: clinically indistinguishable from trisomy 18 distal 1/3 -> : partial clinical picture of trisomy 18 with a longer survival and less profound mental retardation

Clinical Features

Dysmorphic Features

1. Facial

  • microcephaly with prominent occiput
  • narrow bifrontal diameter
  • short palpabral fissures
  • low-set malformed ears
  • cleft lip +/- palate
  • narrow palatal arch
  • micrognathia

2. Skeletal

  • neck - webbed
  • chest - short sternum, widely spaced nipples
  • hips - small pelvis, congenital dislocation of the hips, limited hip abduction
  • extremities - phocomelia, rockerbottom feet or equinovarus, short dorsiflexed big toes, fixed flexion deformity of the fingers (overlapping of the 2nd and 5th fingers over the 3rd and 4th fingers), simple arch pattern of the fingers and toes, hypoplasia of fingernails, single crease of 5th finger or all fingers (absence of interphalangeal flexion creases), simian crease

Organ Malformations

1. Central Nervous System

  • severe mental retardation
  • hypotonia -> hypertonia
  • neural tube defects
  • poor suck and weak cry
  • failure to thrive
  • ocular anomalies

2. Respiratory

  • apnea

3. Cardiovascular( >95%)

  • major: VSD, ASD, PDA
  • minor: transposition, ToF, coarctation, anomalous coronary artery, dextrocardia, aberrant subclavian artery, arteriosclerosis, PS, bicuspid aortic and/or pulmonic valves

4. Gastrointestinal

  • inguinal, umbilical, and/or diaphragmatic hernia
  • congenital defects: diastasis recti, heterotopic pancreas, malrotation, Meckel's, tracheoesophageal fistula

5. Genitourinary

  • cryptorchidism
  • congenital defects: double ureter, ectopic kidney, horseshoe kidney, hydronephrosis, polycystic kidney

Investigations

Imaging Studies

  • to rule out organ malformations:
  • cardiovascular anomalies - Echo
  • gastrointestinal anomalies - Barium Swallow, Endoscope
  • genitourinary anomalies - Ultrasound

Karyotyping

Management

Supportive, very poor prognosis.

  • 30% dying by 1 month of age
  • 50% dying by 2 months of age
  • 90% dying by 12 months of age

Genetic counselling, recurrence rate depends on genotype.

(modified from original 1999 Pedbase entry)

References

  1. <pubmed>13819419</pubmed>
  2. <pubmed>14430807</pubmed>
  3. <pubmed>13831938</pubmed>
  4. <pubmed>22492767</pubmed>
  5. 5.0 5.1 <pubmed>23088440</pubmed>| Orphanet J Rare Dis.
  6. <pubmed>20466091</pubmed>

Reviews

<pubmed></pubmed> <pubmed></pubmed> <pubmed></pubmed> <pubmed>23088440</pubmed>

Articles

Search Pubmed

Search Pubmed: trisomy 13 | Edwards Syndrome

External Links

Glossary Links

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