Trisomy 18 Clinical Presentation

  • Author: Harold Chen, MD, MS, FAAP, FACMG; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Aug 11, 2011
 

History

Prenatal history in trisomy 18

  • Maternal polyhydramnios possibly related to defective sucking and swallowing reflexes in utero
  • Oligohydramnios secondary to renal defects
  • Disproportionately small placenta
  • Single umbilical artery
  • Weak fetal activity
  • Fetal distress

Clinical history in trisomy 18

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Physical

  • Neurological
    • Delayed psychomotor development and mental retardation (100%)
    • Neonatal hypotonia followed by hypertonia, jitteriness, apnea, and seizures
    • Malformations (eg, microcephaly, cerebellar hypoplasia, meningoencephalocele, anencephaly, hydrocephaly, holoprosencephaly, Arnold-Chiari malformation, hypoplasia or aplasia of the corpus callosum, defective falx cerebri, frontal lobe defect, migration defect, arachnoid cyst, myelomeningocele)
  • Cranial - Microcephaly, elongated skull, narrow bifrontal diameter, wide fontanels, and prominent occiput
  • Facial - Microphthalmia, ocular hypertelorism, epicanthal folds, short palpebral fissures, iris coloboma, cataract, corneal clouding, abnormal retinal pigmentation, short nose with upturned nares, choanal atresia, micrognathia or retrognathia, microstomia, narrow palatal arch, infrequent cleft lip and cleft palate, preauricular tags and low-set, and malformed ears (faunlike with flat pinnae and a pointed upper helix)
  • Skeletal - Severe growth retardation, characteristic hand posture (ie, clenched hands with the index finger overriding the middle finger and the fifth finger overriding the fourth finger), camptodactyly, radial hypoplasia or aplasia, thumb aplasia, syndactyly of the second and third digits, arthrogryposis, rocker-bottom feet with prominent calcanei, talipes equinovarus, hypoplastic nails, dorsiflexed great toes, short neck with excessive skin folds, short sternum, narrow pelvis, and limited hip abduction
  • Cardiac
  • Pulmonary -Pulmonary hypoplasia and abnormal lobation of the lung
  • GI -Omphalocele, malrotation of the intestine, ileal atresia, common mesentery, Meckel diverticulum, esophageal atresia with or without tracheoesophageal fistula, diaphragmatic eventration, prune belly anomaly, diastasis recti, absent gallbladder, absent appendix, accessory spleens, exstrophy of Cloaca, pyloric stenosis, imperforate or malpositioned anus, pilonidal sinus, and hernias (ie, umbilical, inguinal, diaphragmatic)
  • Genitourinary
    • Micromulticystic kidneys, double ureters, megaloureters, hydroureters, hydronephrosis, horseshoe kidneys, and unilateral renal agenesis
    • Cryptorchidism, hypospadias, and micropenis in males
    • Hypoplasia of labia and ovaries, bifid uterus, hypoplastic ovaries, and clitoral hypertrophy in females
  • Endocrine - Thymic hypoplasia, thyroid hypoplasia, and adrenal hypoplasia
  • Dermal (ie, dermatoglyphics) - Increased number of simple arches on the fingertips, transverse palmar crease, increased atd angle, and clinodactyly of the fifth fingers with a single flexion crease
  • Fetal trisomy 18 phenotype[7]
    • Aplasia and duplication of thumbs may be observed.
    • Bilateral and median cleft lip and palate is associated with fetal trisomy 18, as is the concomitant occurrence of facial clefts with arthrogryposis of the joints and holoprosencephaly in fetal trisomy 18.
  • Phenotypic spectrum of mosaic trisomy 18[8]
    • Phenotype of individuals with mosaic trisomy 18, in general, widely varies. Some individuals who have the complete trisomy 18 (typical Edwards syndrome) phenotype experience early death whereas others are phenotypically completely normal. The latter group is exemplified by several normal-appearing adults with mosaic trisomy 18 who were identified only after giving birth to children with complete trisomy 18.
    • Anomalies widely vary, most at low frequencies, including microcephaly, delayed bone age, brachydactyly, congenital heart defects, developmental delay, short stature, and premature ovarian failure.
    • Intellectual capabilities range from profound mental retardation to above-average intelligence. No correlation between the percentage of trisomic cells in either fibroblasts or leukocytes and the individual’s phenotype or intellectual function is noted.
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Causes

  • Full trisomy 18 is responsible for 95% of Edwards syndrome cases. Mosaicism and translocations cause few cases. An extra chromosome 18 is responsible for the phenotype.
  • The incidence rate increases with advanced maternal age. In approximately 90% of cases, the extra chromosome is maternal in origin, with meiosis II errors occurring twice as frequently as meiosis I errors. This is in contrast to other human trisomies, which exhibit a higher frequency of nondisjunction in maternal meiosis I. Among cases resulting from paternal nondisjunction, most are the result of postzygotic mitotic errors.
  • Although full trisomy results from meiotic nondisjunction, mosaic trisomy is due to postzygotic mitotic nondisjunction. Mosaic trisomy 18 occurs when both a trisomy 18 cell line and a normal cell line are present in the same individual. Mosaic trisomy 18 accounts for approximately 5% of trisomy 18 cases.[9] The clinical phenotype varies depending on the level of mosaicism and the tissue involved and ranges from the complete trisomy 18 phenotype to no dysmorphic features and normal intelligence.[10]
  • Translocation trisomy gives rise to partial trisomy 18 syndrome. Partial trisomy 18 occurs when a segment of chromosome 18 is present in triplicate, often resulting from a balanced translocation carried by one parent. It accounts for approximately 2% of trisomy 18 cases.
  • The smallest extra region necessary for expression of serious anomalies of trisomy 18 appears to be 18q11-12.
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Contributor Information and Disclosures
Author

Harold Chen, MD, MS, FAAP, FACMG  Professor, Departments of Pediatrics, Obstetrics and Gynecology, and Pathology, Director of Genetic Laboratory Services, Louisiana State University Medical Center

Harold Chen, MD, MS, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics, American Medical Association, and American Society of Human Genetics

Disclosure: Nothing to disclose.

Specialty Editor Board

Michael Fasullo, PhD  Senior Scientist, Ordway Research Institute; Associate Professor, State University of New York at Albany; Adjunct Associate Professor, Center for Immunology and Microbial Disease, Albany Medical College

Michael Fasullo, PhD is a member of the following medical societies: American Society for Biochemistry and Molecular Biology, Environmental Mutagen Society, Genetics Society of America, and Radiation Research Society

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

David Flannery, MD, FAAP, FACMG  Vice Chair of Education, Chief, Section of Medical Genetics, Professor, Department of Pediatrics, Medical College of Georgia

David Flannery, MD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics and American College of Medical Genetics

Disclosure: Nothing to disclose.

Paul D Petry, DO, FACOP, FAAP  Consulting Staff, Freeman Pediatric Care, Freeman Health System

Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

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Infant with Edwards syndrome. Note microphthalmia, micrognathia/retrognathia, microstomia, low set/malformed ears, short sternum, and abnormal clenched fingers.
Note the characteristic clenched hand with the index finger overriding the middle finger and the fifth finger overriding the fourth fingers.
A G-banded karyotype showing 47,XY,+18.
Note a rocker-bottom foot with prominent calcaneus.
Hands of a fetus with Edwards syndrome. Note that fetus typically presents with overlapping digits with the second and fifth fingers overriding the third and fourth fingers respectively. Overall posturing of the wrists and fingers suggests contractures.
 
 
 
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