September 14, 2016
Years published: 1992, 2000, 2002, 2003, 2016
NORD gratefully acknowledges Ida Vogel, MD, PhD, Consultant and Associate Professor, Department of Clinical Genetics, Aaarhus University Hospital, Denmark for assistance in the preparation of this report.
Pallister-Killian mosaic syndrome is a rare chromosomal disorder caused by the presence of at least four copies of the short arm of chromosome 12 instead of the normal two. Major symptoms may include a coarse face with a high forehead, sparse hair on the scalp, an abnormally wide space between the eyes, a fold of the skin over the inner corner of the eyes, and a broad nasal bridge with a highly arched palate. Intellectual disability, loss of muscle tone, and streaks of skin lacking color are often present.
In 1977, the syndrome was reported independently by Pallister, and again in 1981 by Teschler-Nicola and Killian. However, it wasn’t until 2003 when Pallister performed chromosome an analysis on skin fibroblast that the presence of tetrasomy 12p was found.
Individuals with Pallister-Killian mosaic syndrome typically have low muscle tone at birth (hypotonia), sparse scalp hair, a high forehead, a coarse face, an abnormally wide space between the eyes, a broad nasal bridge, a highly arched palate, a fold of the skin over the inner corner of the eyes, and large ears with lobes that are thick and protrude outward.
Infants that are born with significant hypotonia can experience problems with feeding, breathing, walking and standing. About seventy percent of affected individuals are unable to walk without assistance.
Additional features frequently found in affected individuals may include streaks of skin in which there is no color (hypopigmentation); extra nipples; seizures; droopy upper eyelids, crossed eyes (strabismus); joints that will not move (contractures); and delays in perceiving, recognizing, judging, sensing, reasoning or imagining (cognitive delays). Intellectual disability and difficulties with speech development often occur as well. In rare cases, affected children may experience hearing loss.
Congenital heart defects, hernias of the diaphragm, a narrowing of the external auditory canal (stenosis) and an abnormal opening in the anus have also been associated with Pallister-Killian Mosaic Syndrome. Some affected individuals may have an underdeveloped (hypoplastic) lung, abnormalities of the genitourinary system, and skeletal malformations. Symptoms may vary according to which tissue has the additional chromosomal material, and may also affect each side of the body unevenly.
Pallister-Killian mosaic syndrome is caused by the presence of four copies of the short arm of chromosome 12 instead of the normal two. The extra two copies of the short arm of chromosome 12 (12p) usually appear as a single chromosome (isochromosome) and are sometimes present in some but not all cells examined (mosaicism). The chromosome abnormality in Pallister-Killian mosaic syndrome is limited to specific cell types. The mechanism and parental origin of the isochromosome 12p can usually not be determined. The extra genetic material disrupts the normal course of development and results in the signs and symptoms of this disorder.
Pallister-Killian mosaic syndrome is not inherited; the disorder is the result of a random event during the formation of reproductive cells, it usually occurs in the mother. Typically, an error in cell division (nondisjunction) causes a reproductive cell to contain an isochromosome 12p.
Pallister-Killian mosaic syndrome is a very rare disorder that affects males and females in equal numbers. The exact prevalence is unknown; this disorder may be underdiagnosed because it is difficult to detect in patients with mild symptoms. Currently, more than 150 people with this disorder have been reported in the medical literature.
Diagnosis is usually made from a chromosome study of skin cells (fibroblasts) that reveals 47 chromosomes including an extra small chromosome that has two short (p) arms and no long (q) arm (isochromosome). Chromosomal microarray, the first tier analyses in malformation syndromes, can also reveal Pallister Killian syndrome, if the right tissue is selected. Blood chromosome analyses usually shows normal number of chromosomes, but some affected persons have some blood cells (lymphocytes) with an isochromosome 12p. Cells with high cell turnover such as blood may lose the additional chromosomal material over time, and thereby give a false negative result on blood. Therefore, a normal blood chromosomal analysis does not completely rule out Pallister-Killian mosaic syndrome.
Two individuals with Pallister-Killian mosaic syndrome have been reported with five copies (hexasomy) for chromosome 12p.
Pallister-Killian mosaic syndrome can be diagnosed before birth (prenatally) by removing a small amount of fluid that is in the womb during pregnancy (amniocentesis) or by removing a small number of cells from outside the sac where the fetus develops (chorionic villous sampling). Cell cultures may yield a false negative however, and a normal chromosomal analysis does not completely rule out the condition.
There is no specific therapy for individuals with Pallister-Killian mosaic syndrome. Affected children may benefit from early intervention programs and special education. Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.
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