Last updated:
10/14/2025
Years published: 1996, 2001, 2009, 2025
NORD gratefully acknowledges Gioconda Alyea, MD (FMG), MS, National Organization for Rare Disorders, for the preparation of this report.
Tetrasomy 18p is a very rare chromosomal disorder in which the short arm of the 18th chromosome (18p) appears four times (tetrasomy) rather than twice in cells of the body. People with a normal chromosomal make-up (karyotype) have two 18th chromosomes, both of which have a short arm (“18p”) and a long arm (“18q”). However, in people with tetrasomy 18p, four short arms (18p) are present in cells of the body rather than the normal two.1,2,3,4
The symptoms of tetrasomy 18p vary from person to person. Many affected people have abnormalities of the head and facial (craniofacial) area, malformations of the spine, hands, and/or feet, neuromuscular abnormalities, such as increased muscle tone (hypertonia), increased reflex reactions (hyperreflexia), and difficulty coordinating movement, kidney (renal) malformations and/or additional physical abnormalities.1-6
In addition, children and adults with tetrasomy 18p often have moderate to severe intellectual disability, limitations in speech and/or behavioral abnormalities. In most people, tetrasomy 18p is the result of a spontaneous (de novo) genetic change (variant) early in embryonic development that occurs for unknown reasons (sporadic). 5-9 The word “tetrasomy” is derived from “tetra,” the Greek word for “four.”10
People with tetrasomy 18p can have a wide range of physical, developmental and medical concerns that vary from person to person.
Moderate to severe intellectual disability is common as well as delayed or limited speech and vocabulary development. Behavioral challenges may also be present. Low birth weight is very common, as well as feeding difficulties and frequent vomiting. Failure to thrive may occur (without proper nutritional support). In addition, the following symptoms have been described:1-6, 11-13
Tetrasomy 18p is a rare chromosomal disorder in which the short arm of chromosome 18 (18p) appears four times (tetrasomy) rather than twice in the cells of the body. 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 sections known as bands that are numbered. Chromosomal bands are visible patterns on chromosomes seen under a microscope after special staining techniques, and each band reflects areas of DNA that differ in composition, structure and gene density. They are numbered and named according to the chromosome number, arm (p or q) and region.10
Individuals with a normal chromosomal make-up (karyotype) have two 18th chromosomes, both of which consist of a short arm (18p), a long arm (18q), and a narrowed region at which the two arms are joined (centromere). However, people with tetrasomy 18p have an extra chromosome known as an “isochromosome” that consists of two identical short arms (18p) and a centromere. An isochromosome is a chromosome with identical arms on each side of the centromere. Therefore, a total of four short arms (18p) are present in cells of the body rather than the normal two, resulting in the symptoms and physical findings that characterize this disorder.10
The formation of isochromosome 18p is thought to occur due to errors during the development of the egg cell, specifically during a stage called maternal meiosis II. During meiosis II, chromosomes are supposed to separate evenly, but sometimes they do not, a mistake known as nondisjunction. In addition to this, the chromosome may divide incorrectly at its center, a region called the centromere, or undergo an unusual rearrangement known as a U-shaped exchange. These rare errors can lead to the creation of an isochromosome, which is a chromosome made up of two identical short arms from chromosome 18, rather than one short and one long arm as normally seen. This can result in genetic imbalances that may affect a person’s development and health.4, 5,12-17
In most affected people, tetrasomy 18p has occurred because of a spontaneous (de novo) change very early in embryonic development that happened for unknown reasons (sporadically) and was not inherited from the parents. In these people, the parents usually have normal chromosomes and a relatively low risk of having another child with the chromosomal abnormality.4,5
However, there have been rare cases in which a parent also has an extra 18p isochromosome in all cells or only on some cells, a condition known as chromosomal mosaicism.5, 6,12,15 Chromosomal mosaicism describes cases in which only a percentage of cells contain the chromosomal abnormality while other cells have a normal chromosomal makeup. In such instances, it is believed that tetrasomy 18p may have been inherited and that the chances are greater of having another child with the chromosomal abnormality. Chromosomal analysis and genetic counseling are recommended for parents of an affected child.
Tetrasomy 18p is a very rare chromosomal disorder that appears to affect males and females equally. As of 2018, approximately 108 cases have been reported in the medical literature.4 Globally, it is one of the more common isochromosomes. It is seen in about 1 in every 180,000 live births and fewer than 5,000 people in the U.S. are estimated to have the disorder.16
According to the small supernumerary marker chromosomes database built by Dr. Thomas Liehr, from the Institute of Human Genetics and Anthropology in Berlin, around 387 cases of isochromosome 18p have been reported worldwide. This database is an online, comprehensive resource collecting information and case reports on small supernumerary marker chromosomes (sSMCs).18
Tetrasomy 18p may be suspected based on a thorough clinical evaluation and characteristic physical findings. The diagnosis can be confirmed with standard or specialized chromosomal studies. A standard karyotype can detect tetrasomy 18p by identifying an extra, small chromosome (a supernumerary marker chromosome) that is an isochromosome of the 18p arm. However, for cases with mosaicism (where not all cells have the extra chromosome) or when the genetic change is complex, a karyotype may need to be combined with other techniques like chromosome microarray analysis or fluorescence in situ hybridization (FISH]) for a complete and accurate diagnosis. Additional diagnostic tests may also be conducted to help detect and/or characterize certain abnormalities that may be associated with the disorder.4,5,16-22
A karyotype test is a type of genetic testing. It looks at the size, shape and number of chromosomes in a sample of cells from the body. It is used to identify large-scale abnormalities like extra or missing chromosomes. FISH is a technique that uses fluorescent probes to detect specific, often smaller, DNA sequences or genes that are not visible with a karyotype.
The diagnosis of tetrasomy 18p can also be made before birth (prenatally) by specialized tests such as ultrasound, fetal blood sampling, amniocentesis and/or chorionic villus sampling (CVS). During fetal ultrasonography, reflected sound waves are used to create an image of the developing fetus. Ultrasound studies may reveal characteristic findings that suggest a chromosomal disorder or other developmental abnormalities in the fetus. During fetal blood sampling, blood is drawn with a needle that is guided via ultrasound into the umbilical vein. With amniocentesis, a sample of fluid that surrounds the developing fetus is removed and analyzed, while CVS involves the removal of tissue samples from a portion of the placenta. Chromosomal analysis performed on fluid or tissue samples (i.e., obtained via fetal blood sampling, amniocentesis, or CVS) may reveal the presence of tetrasomy 18p.4, 20-22
Treatment
There is no cure for tetrasomy 18p, so treatment focuses on managing symptoms through supportive care and a multidisciplinary team. Management typically includes genetic counseling and referrals to specialists such as ophthalmologists, cardiologists, orthopedic surgeons and neurologists. Physical, occupational and speech therapy are also important.4
Treatment is tailored to the individual’s specific symptoms. This may involve surgery to correct craniofacial, ocular, skeletal, kidney, or other structural abnormalities, depending on their type and severity.
Ongoing care is supportive and aimed at helping individuals reach their full potential. This often includes special education, therapeutic services, and access to medical, social, and vocational support. Genetic counseling is also recommended for families.
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For information about clinical trials sponsored by private sources, contact:
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For information about clinical trials conducted in Europe, contact:
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