NORD gratefully acknowledges Anthony Smyth and Grace Seibert, NORD Editorial Interns from the University of Notre Dame, and Deborah A. Bruns, PhD, Professor, Special Education Program, Department of Counseling, Quantitative Methods and Special Education, Southern Illinois University Carbondale, for assistance in the preparation of this report.
Trisomy 18 is a rare chromosomal disorder in which all or a critical region of chromosome 18 appears three times (trisomy) rather than twice in cells of the body. In some children, the chromosomal abnormality may be present in only a percentage of cells, whereas other cells contain the typical chromosomal pair (mosaicism).
Trisomy 18 may be a life-threatening condition; some affected die before birth or within the first month of life. Some individuals have survived to their teenage years and beyond, with a range of medical and developmental needs. Trisomy 18 is usually not inherited but occurs by chance.
Depending on the specific location of the duplicated (trisomic) portion of chromosome 18 and the percentage of cells, symptoms and findings can be extremely variable from person to person. The majority of affected infants experience growth deficiency, feeding and breathing difficulties, and developmental delays. Individuals with trisomy 18 also have distinctive malformations of the head and facial (craniofacial) area as well as of the hands and feet, possible skeletal deformities, genitourinary issues and heart defects present at birth (congenital). Congenital heart defects and associated respiratory difficulties may lead to potentially life-threatening complications during infancy or childhood. Treatment is dependent upon the specific symptoms present, recommendations from the medical team and parent/family preference.
The symptoms associated with trisomy 18 are extremely variable. Severity is dependent upon the percentage of cells that contain the third copy of the chromosome (mosaicism). Certain findings before birth (prenatally) and during infancy are considered characteristic of trisomy 18. In many patients, there is decreased movement in utero.
Affected infants may have poor suckling ability and associated feeding difficulties that can be supported with tube feeding, failure to grow and gain weight at the expected rate (failure to thrive), and distinctive malformations of the head and facial (craniofacial) area. Many infants with trisomy 18 also have malformations of the hands and feet, additional skeletal defects, and structural abnormalities of the heart (congenital heart defects) and undescended testes in affected males (cryptorchidism).
Skeletal muscles and underlying connective and fatty tissues (subcutaneous and adipose tissue) may be underdeveloped (hypoplastic). Additional characteristics during infancy may include diminished muscle tone (hypotonia) followed by unusually increased tone (hypertonia) and muscle stiffness (rigidity) that is often due to tremors or seizures; a weak cry; decreased response to environmental sounds due to anatomical abnormities of the ear; and/or repeated episodes in which there is a temporary cessation of breathing (apneic episodes).
Many infants with trisomy 18 also have distinctive characteristics of the craniofacial region. These may include a small head (microcephaly) that appears unusually long and narrow (dolichocephaly); a prominent back region of the head (occiput); a small mouth (microstomia); incomplete closure of the roof of the mouth (cleft palate) and/or an abnormal groove in the upper lip (cleft lip); a small jaw (micrognathia); or a short, webbed neck. Affected infants may also have an upturned nose; low-set, malformed ears; widely spaced eyes (ocular hypertelorism) with slanted or narrow eyelid folds (palpebral folds); and vertical skin folds covering the eyes’ inner corners (epicanthal folds).
Trisomy 18 may also be characterized by additional eye (ocular) malformations. For example, there may be drooping of the upper eyelids (ptosis) and an inability to completely close the eyes. Some affected infants also have clouding of the normally transparent front regions of the eyes (corneas); loss of transparency of the lenses (cataracts); or unusual smallness of the eyes (microphthalmia). Additional ocular malformations may include abnormal deviation of one eye in relation to the other (strabismus); inequality in the diameter of the pupils (anisocoria); rapid involuntary eye movements (nystagmus); and/or a decreased response to visual stimuli.
Many infants with trisomy 18 also have characteristic malformations of the hands and feet. The hands are typically clenched, with overlapping of the index finger (second finger) over the third finger and the “pinky” (fifth finger) over the fourth. Frequent findings also include unusual skin ridge patterns (dermatoglyphics) on the fingers and palms; underdeveloped (hypoplastic) nails, particularly those of the fifth fingers and toes; and abnormal deviation of the great toes (hallux) in an upwardly bent position (dorsiflexion). In some children, additional irregularities may be present such as the presence of extra fingers or toes (polydactyly); webbing (syndactyly) of one or more toes; or the feet appear shaped like the rocker of a rocking chair (“rocker-bottom feet”) with abnormal prominence of the heel bones (calcaneus). Some infants also have a foot deformity in which the heels are turned inward and the soles are flexed or clubfeet (talipes equinovarus).
Many infants with trisomy 18 also have skeletal malformations such as a short breastbone (sternum); a small pelvis with limited outward movements (abduction) of the hips; or abnormalities of the ribs. There may be defects of certain bones of the spinal column (vertebrae), including sideways curvature of the spine (scoliosis); underdevelopment of one half of certain vertebrae (hemivertebrae); or abnormal fusion of vertebrae.
As mentioned above, in males with the disorder, the testes may fail to descend into the scrotum (cryptorchidism). Trisomy 18 may also be associated with additional genital malformations. In some affected males, there may be division of the scrotum into two parts (bifid scrotum) and/or abnormal placement of the urinary opening (hypospadias), such as on the underside of the penis. In some females with the disorder, there is underdevelopment (hypoplasia) of the outer skin folds (labia majora) surrounding the vaginal opening and abnormal prominence of the relatively small, sensitive protrusion (clitoris) that forms part of the female external genitalia.
Trisomy 18 is also often characterized by structural heart (cardiac) defects that are present at birth (congenital heart defects). Many affected infants have an abnormal opening in the fibrous partition (septum) that separates the lower chambers of the heart (ventricular septal defect; VSD). Another common finding is abnormal persistence of the fetal opening between the two major arteries (aorta, pulmonary artery) that emerge from the heart (patent ductus arteriosus; PDA). Additional cardiac defects may be present including narrowing (stenosis) of the opening between the right ventricle and the artery that carries oxygen-deficient blood to the lungs (pulmonary artery); narrowing of the major artery that transports oxygen-rich blood from the heart to all parts of the body (coarctation of the aorta); and/or abnormalities of heart valves.
Some infants with trisomy 18 have malformations of the abdominal wall and the kidneys. For example, there may be protrusion of portions of the intestine through an abnormal opening in muscles of the groin (inguinal hernia) or the abdominal wall near the navel (umbilical hernia). Some infants with trisomy 18 have an omphalocele, a birth defect in which varying amounts of intestines or other abdominal organs (viscera), covered by a membrane-like sac, protrude through an opening in the abdominal wall near the navel. Some affected infants may have kidneys that are abnormally positioned (ectopic) or joined together (horseshoe kidneys) or contain multiple cysts (polycystic kidneys). There may also be swelling of the kidneys with urine due to narrowing or blockage of the tubes that carry urine from the kidneys to the bladder (hydronephrosis).
Some affected infants may also have malformations of the brain and spinal cord (central nervous system; CNS). These may include absence (agenesis) or underdevelopment (hypoplasia) of the thick band of nerve fibers connecting the two hemispheres of the brain (corpus callosum); protrusion of part of the spinal cord and its surrounding membranes (meninges) through an abnormal opening in the spinal column (myelomeningocele); or other malformations.
Congenital heart defects, respiratory difficulties (e.g., apneic episodes, aspiration), or other abnormalities associated with the disorder may lead to potentially life-threatening complications during infancy or childhood.
Trisomy 18 is also typically characterized by intellectual disability, along with delayed verbal, and motor development. Yet, children do communicate through facial expressions, gestures and vocalizations. Some are able to use augmentative communication devices and systems. Mobility needs can be addressed through orthotics, gait trainers and other assistive devices as tolerated. Individuals with trisomy 18 recognize family members and caregivers and can display a range of emotions including indicating preferences for items and people in their environment.
Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as “p” and a long arm identified by the letter “q.” Chromosomes are further subdivided into bands that are numbered.
In individuals with trisomy 18, all or a particular region of chromosome 18 is present three times (trisomy) rather than twice within cells. This extra genetic material from the third copy of the chromosome disrupts typical development and causes characteristic features of the condition. In about 5% of patients, only some cells in the body contain the extra 18th chromosome (mosaicism). Very rarely, an extra piece of chromosome 18 is attached to another chromosome (translocation trisomy 18 or partial trisomy 18). If only part of the long (q) arm of chromosome 18 is present in three copies, the symptoms may be less severe than in people with full trisomy 18.
Duplication of a specific region or regions of chromosome 18 is responsible for the symptoms and findings that characterize the condition. The severity and range of symptoms may depend on the length and location of the duplicated portion of the chromosome as well as the percentage of cells with the duplication. In individuals with partial trisomy of chromosome 18 who have characteristic symptoms of the disorder, evidence suggests that a critical region associated with trisomy 18 is duplication at band 18q11.
In most individuals with the disorder, duplication of chromosome 18 is caused by spontaneous (de novo) errors during the division of reproductive cells in one of the parents (e.g., nondisjunction during meiosis). Reports suggest that the risk of such errors may increase with advanced parental age. In cases in which only a percentage of cells contain three copies (mosaicism), errors may also occur during cellular division after fertilization (mitosis).
In some individuals, trisomy 18 may result from a translocation involving chromosome 18 and another chromosome. Translocations occur when regions of certain chromosomes break off and are rearranged, resulting in shifting of genetic material and an altered set of chromosomes. Such translocations may occur spontaneously for unknown reasons (de novo) or be transmitted by a parent who is a carrier of a “balanced” translocation. (If a chromosomal rearrangement is balanced–i.e., consists of an altered but balanced set of chromosomes–it is usually harmless to the carrier. However, balanced translocations are sometimes associated with a higher risk of abnormal chromosomal development in the carrier’s offspring. Chromosomal testing may determine whether a parent has a balanced translocation.) A person with a balanced translocation had an increased risk with each pregnancy to have a child with trisomy 18.
Trisomy 18 affects females more frequently than males by a ratio of three or four to one. Large population surveys indicate that it occurs in about one in 5,000 to 7,000 live births. The frequency of trisomy 18 appears to increase with advancing maternal age. Reports indicate mean maternal age is 32.5 years. There are also reports of mothers in their late teens and early 20’s.
A diagnosis of trisomy 18 may be suspected before birth based upon specialized testing such as fetal ultrasonography and maternal serum screening. During fetal ultrasonography, reflected sound waves create an image of the developing fetus, potentially revealing findings that may suggest a chromosomal disorder or other abnormalities. In addition, screening tests that reveal abnormal levels of certain “markers” in the mother’s blood may suggest an increased risk of trisomy 18 or other chromosomal abnormalities (e.g., Down syndrome). Such tests measure the levels of specific substances in the blood, including alpha-fetoprotein (AFP); human chorionic gonadotropin (hCG); unconjugated estriol; or other markers. If such screening studies reveal abnormal levels of these markers, additional testing may be recommended, such as amniocentesis or chorionic villus sampling (CVS) for chromosomal analysis. During amniocentesis, a sample of fluid that surrounds the developing fetus is removed and analyzed. CVS involves the removal of tissue samples from a portion of the placenta.
The diagnosis of trisomy 18 may also be confirmed after birth based on a thorough clinical evaluation, detection of characteristic physical findings, and chromosomal analysis. For infants diagnosed with trisomy 18, careful monitoring and specialized testing may be conducted to ensure early detection and appropriate management of conditions associated with trisomy 18 such as cardiac defects and kidney concerns.
The treatment of trisomy 18 is directed toward the specific symptoms in each affected individual. Treatment often requires the coordinated efforts of a multidisciplinary team of medical professionals.
For many affected infants, supportive measures may be required to improve feeding and the intake of necessary nutrients. Such measures may include the delivery of liquid nutrients to the stomach through a tube inserted through the nose (nasogastric tube feeding) or stomach (gastrostomy). In addition, oxygen therapy may be required to ensure sufficient oxygen supply to bodily tissues or placement of a tracheostomy. Some individuals need support from a ventilator after invasive procedures or surgeries and most can be successfully weaned.
Recommended treatment may include surgical correction of certain abnormalities associated with the disorder which may help to improve quantity and quality of life. The surgical procedures performed will depend upon the nature and severity of the anatomical malformations, their associated symptoms, and other unique factors. Individuals have received palliative and more aggressive interventions for cardiac malformations. For example, in recent years, many individuals have had successful cardiac surgery to correct VSD.
A prevalent symptom among individuals with trisomy 18 is the presence of malignancies. It is recommended to have early imaging and lab exams done at specific intervals. For example, monitoring for Wilms tumor (a rare kidney cancer) is recommended every three months by abdominal ultrasound for children over one year of age. Nephroblastomatosis is commonly seen as a precursor to Wilms tumor. The possibility of hepatoblastoma (liver cancer) has also been reported in children with trisomy 18. Chemotherapy and surgical resection for patients with stable cardiac function can prolong life.
A team approach for children with this disorder may include early intervention (birth to age three services) special education, physical therapy, occupational therapy, speech therapy in addition to necessary medical professionals and social services including in home nursing care and respite care as feasible. Coordinated treatment for this disorder is symptomatic and supportive.
Genetic counseling is recommended for families with children with trisomy 18.
This resource suggests a shared decision making model to help families and physicians provide the most optimal patient care.
The Tracking Rare Incidence Syndromes (TRIS) project is designed to raise awareness and provide support for families and professionals involved in the care of children and adults with rare trisomy conditions. The TRIS project seeks to increase the knowledge base on rare incidence trisomy conditions, and to make this information available to families and interested educational, medical and therapeutic professionals. For more information, contact:
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov.All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
For information about clinical trials sponsored by private sources, contact:
For information about clinical trials conducted in Europe, contact:
Jorde LB, Carey JC, & Bamshad MJ. Medical Genetics e-Book. 2015. Elsevier Health Sciences.
Cassidy SB & Allanson JE. Management of genetic syndromes. 2010. John Wiley & Sons.
Carey JC. Trisomy 18 Syndrome. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:88.
Farmakis SG, Barnes AM, et al. Solid tumor screening recommendations in trisomy 18. Am J Med Genet. 2019;179A:455-466.
Janvier A, Farlow B, Barrington KJ, Bourque CJ, Brazg T, & Wilfond B. Building trust and improving communication with parents of children with Trisomy 13 and 18: A mixed-methods study. Palliative Medicine 2019; 0269216319860662.
Kato E, Kitase Y, Tachibana T, et al. Factors related to survival discharge in trisomy 18: A retrospective multicenter study. American Journal of Medical Genetics Part A. 2019; 179:1253–1259.
Taira R, Inoue H, Sawano T, et al. Management of apnea in infants with trisomy 18. Developmental Medicine & Child Neurology 2019: Nov 25. doi: 10.1111/dmcn.14403. [Epub ahead of print]
Alkhamdi MA, Diogo R, et al. Detailed Musculoskeletal Study of a Fetus with Trisomy-18 (Edwards Syndrome) with Langer’s Axillary Arch, and Comparison with Other Cases of Human Congenital Malformations. J Anat Sci Res. 2018;1:1-8.
Inuoe A, Suzuki R, et al. Therapeutic experience with hepatoblastoma associated with trisomy 18. Pediatr Blood Cancer. 2018;65:e27093.
Peterson R, Calamur N, Fiore A, Huddleston C, & Spence K. Factors influencing outcomes after cardiac intervention in infants with trisomy 13 and 18. Pediatric Cardiology 2018; 39(1): 140-147.
Kosiv KA, Gossett JM, Bai S, & Collins RT. Congenital heart surgery on in-hospital mortality in trisomy 13 and 18. Pediatrics 2017; 140(5): e20170772.
Patterson F. Taylor G, et al. Transitions in Care for Infants with Trisomy 13 or 18. Amer J Perinatol. 2017;34:887-894.
Peterson JK, Kochilas LK, Catton KG, Moller JH, & Setty SP. Long-term outcomes of children with trisomy 13 and 18 after congenital heart disease interventions. The Annals of Thoracic Surgery 2017; 103(6): 1941-1949.
Andrews SE, Downey AG, et al. Shared decision making and the pathways approach in the prenatal and postnatal management of the trisomy 13 and trisomy 18 syndromes. Am J Med Genet C Semin Med Genet. 2016;172:257-263.
Bruns DA, & Martinez A. An analysis of cardiac defects and surgical interventions in 84 cases with full trisomy 18. American journal of medical genetics Part A 2016; 170(2): 337-343.
Carey JC, & Barnes AM. Wilms tumor and trisomy 18: Is there an association? In American Journal of Medical Genetics Part C: Seminars in Medical Genetics 2016; 172(3): 307-308.
Donovan JH, Krigbaum G & Bruns DA.Medical interventions and survival by gender of children with trisomy 18. In American Journal of Medical Genetics Part C, Seminars in Medical Genetics 2016;172(3): 272-278.
Josephsen JB, Armbrecht ES, Braddock SR, & Cibulskis CC. Procedures in the 1st year of life for children with trisomy 13 and trisomy 18, a 25‐year, single‐center review. In American Journal of Medical Genetics Part C: Seminars in Medical Genetics 2016;. 172(3):264-271.
Meyer RE, Liu G, Gilboa SM, et al & National Birth Defects Prevention Network. Survival of children with trisomy 13 and trisomy 18: a multi‐state population‐based study. American journal of medical genetics Part A 2016; 170(4): 825-837.
Nelson KE, Rosella LC, et al. Survival and surgical interventions for children with trisomy 13 and 18. JAMA. 2016;316:420-428.
Satgé D, Nishi M, Sirvent N, & Vekemans M. A tumor profile in Edwards syndrome (trisomy 18). In American Journal of Medical Genetics Part C: Seminars in Medical Genetics 2016;172(3): 296-306.
Bruns DA. Developmental status of 22 children with trisomy 18 and eight children with trisomy 13: implications and recommendations. American Journal of Medical Genetics Part A 2015; 167(8):1807-1815.
Cereda A & Carey JC. The trisomy 18 syndrome. Orphanet Journal of Rare Diseases 2012; 7(1): 81.
Palomaki GE, Deciu C, et al. DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: an international collaborative study. Genet Med. 2012;14:296–305.
Trisomy 18. Genetic and Rare Diseases Information Center (GARD). Trisomy 18. Last updated: 7/7/2015. https://rarediseases.info.nih.gov/diseases/6321/trisomy-18 Accessed Jan 22, 2020.
The information in NORD’s Rare Disease Database is for educational purposes only and is not intended to replace the advice of a physician or other qualified medical professional.
The content of the website and databases of the National Organization for Rare Disorders (NORD) is copyrighted and may not be reproduced, copied, downloaded or disseminated, in any way, for any commercial or public purpose, without prior written authorization and approval from NORD. Individuals may print one hard copy of an individual disease for personal use, provided that content is unmodified and includes NORD’s copyright.
National Organization for Rare Disorders (NORD)
55 Kenosia Ave., Danbury CT 06810 • (203)744-0100