Information on the following diseases can be found in the Related Disorders section of this report:

• Chromosome 12, Partial Trisomy 12P
• Hypomelanosis of ITO

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.

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). Mental retardation 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.
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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. 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.

Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”.
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Pallister-Killian Mosaic Syndrome is a very rare disorder that affects males and females in equal numbers. More than 30 cases of this disorder have been reported in the medical literature.
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Symptoms of the following disorders can be similar to those of Pallister- Killian Mosaic Syndrome. Comparisons may be useful for a differential diagnosis:

Hypomelanosis of ITO is a rare disorder in which the main characteristic is lesions of the skin. A whorl-like lack of pigmentation of the skin may occur on any part of the body except the soles, palms, and scalp. Over half of the patients with this disorder may have seizures, mental retardation, crossed eyes, nearsightedness, a cleft along the edge of the eyeball (coloboma), an abnormally small head and/or an abnormal overgrowth of brain tissue (megalencephaly). Autosomal dominant inheritance has been suggested in some cases.

Chromosome 12, Partial Trisomy 12P, is a rare genetic disorder in which there is a triplicated section of the short arm of the 12th chromosome. Patients with this disorder have a lack of muscle tone (hypotonia), growth retardation, and distinct facial features such as a flat upturned nose with a wide bridge, shallow eye sockets, a vertical fold of the skin over the inner corner of the eye, an upward slant of the opening between the upper and lower eyelids, a long thick lower lip, a large tongue and short broad hands with the fifth finger bent to the side. Chromosome 12, Partial Trisomy 12P affects females twice as often as males.

Diagnosis
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). A blood chromosome study usually shows normal chromosomes, but some affected persons have some blood cells (lymphocytes) with an isochromosome 12p. Fluorescent in situ hybridization (FISH) may be used with specific chromosome 12 DNA probes to detect isochromosome 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).

Treatment
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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Research on birth defects and their causes is ongoing. The National Institutes of Health (NIH) is sponsoring the Human Genome Project which is aimed at mapping every gene in the human body and learning why genes sometimes malfunction. It is hoped that this new knowledge will lead to prevention and treatment of birth defects in the future.

McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:601803; Last Update:3/20/01.

TEXTBOOK
Jones KL. Smith’s Recognizable Patterns of Human Malformation. Philadelphia, PA: W. B. Saunders Company; 1997:208-9.

REVIEWS
Chiesa J, et al., Pallister-Killian syndrome [i(12p)]: first pre-natal diagnosis using cordocentesis in the second trimester confirmed by in situ hybridization. Clin Genet. 1998;54:294-302.

Smulian J, et al., Genetics casebook. Pallister-Killian syndrome. J Perinatol. 1996;16:406-12.

ARTICLES
Schuster M, et al., Severe hearing loss in Pallister-Killian syndrome. ORL J Otorhinolaryngol Relat Spec. 2002;64:343-5.

Doray B, et al., Pallister-Killian syndrome: difficulties of prenatal diagnosis. Prenat Diagn. 2002;22:470-7.

Takakuwa K, et al., A case of mosaic tetrasomy 12p (Pallister-Killian Syndrome) diagnosed prenatally: comparison of chromosome analysis of various cells obtained from the patient. Am J Perinatol. 1997;14:641-43.

Schubert R, et al., Report of two new cases of Pallister-Killian syndrome confirmed by FISH: tissue-specific mosaicism and loss of i(12p) by in vitro selection. Am J Med Genet. 1997;72:106-10.

Schaefer GB, et al., Clinical variability of tetrasomy 12p. Clin Genet. 1997;51:102-08.

Mathieu M, et al., Collaborative study of mosaic tetrasomy 12p or Pallister-Killian syndrome (nineteen fetuses or children). Ann Genet. 1997;40:45-54.