Pallister-Killian syndrome

Definition

Pallister-Killian syndrome (PKS) is a rare chromosome abnormality in which a person has four copies of the short arm of chromosome 12 instead of the normal two copies. Affected individuals have unusual facial features, mental retardation, seizures, patchy color differences in the skin, and various other physical abnormalities. Many fetuses with Pallister-Killian syndrome die during pregnancy or soon after birth.

Description

Pallister-Killian syndrome was first described in 1977. The first two patients Pallister reported were adults with severe mental retardation, unusual facial features, severe lack of muscle strength, and pale areas on their skin. In 1981, Killian and Teschler-Nicola described a child with mental retardation, unusual facial features, pale skin on the face, and absence of hair at the front of the scalp.

Pallister-Killian syndrome may also be called Killian syndrome, Killian/Teschler-Nicola syndrome, Pallister mosaic syndrome, or Teschler-Nicola/Killian syndrome. This syndrome may also be called tetrasomy 12p mosaicism syndrome or isochromosome 12p syndrome based on the characteristic chromosome abnormality detected via laboratory studies. Pallister-Killian syndrome is called mosaic because the characteristic chromosome abnormality that causes the syndrome appears only in a fraction of the total cells examined.

Genetic profile

Pallister-Killian syndrome is a sporadic disorder, which means that it appears to occur at random. The chromosome problem that causes PKS, tetrasomy 12p, does not appear to run in families. Pallister-Killian syndrome is not specifically associated with any specific chemical or environmental exposures.

Tetrasomy 12p is characterized by the presence of four copies of the short arm of chromosome 12, instead of the normal two copies. This chromosome abnormality is not found throughout an affected person's body. Chromosome analysis performed on the blood of persons with Pallister-Killian syndrome virtually always shows normal results. The characteristic chromosome abnormality can, however, be detected via chromosome analysis on skin cells. Through chromosome analysis, tetrasomy 12p is identified due to the presence of what appears to be an extra chromosome composed of two copies of the short arm of chromosome 12. This chromosome composed of two copies of the short arm of chromosome 12 is called an isochromosome. In tetrasomy 12p, there is a total of four copies of the short arm of chromosome 12: there are the two normal copies, plus the two abnormal copies located on the extra isochromosome.

Demographics

Pallister-Killian syndrome occurs at random; however, an association with advanced maternal age (35 years or greater) has long been documented. Though PKS may occur more frequently in babies born to mothers age 35 or older, the syndrome still may occur in babies born to mothers of any age. PKS occurs strictly due to an abnormality of the chromosomes.

Signs and symptoms

Many infants with more severe physical defects associated with PKS will die in utero or shortly after birth. Other persons with Pallister-Killian syndrome have lived at least into their 20s. All persons with PKS have some level of mental retardation or developmental delay.

The features of PKS may vary significantly between affected persons. The most typical person with Pallister-Killian syndrome will have profound mental retardation, delayed development, lack of muscle tone, light- and/or dark-colored areas of skin, lack of scalp hair above the temples, and unusual facial features. The facial features characteristic for Pallister-Killian syndrome include a large forehead, widely spaced eyes with vertical folds of skin at the inner corners, droopy eyelids, short and upturned nose, full cheeks, lengthened distance between the nose and upper lip, and small chin.

Persons with PKS often have deafness, absent or minimal speech, poor vision, and seizures. Individuals with PKS have additionally been reported to have short, wide hands with short fingers, while others have extra fingers or toes. Some affected persons have had cleft palate and some have had a bifid uvula (cleft, or split, uvula). The teeth come in later than normal in persons with PKS. Heart defects may be present and the sac normally surrounding the heart, the pericardium, may be missing. Additionally, there may be small patches of exposed tissue where the skin did not develop.

Many individuals with Pallister-Killian syndrome have been reported to have extra nipples, and some have a hernia around the navel. Some persons with PKS have problems with the intestines or anus. Many have birth defects involving the genitals or internal reproductive organs and others have disorganized or cyst-filled kidneys. A small tail-like stub at the bottom of the spine was reported in at least one person affected with Pallister-Killian syndrome.

The features of PKS change over time. The lack of hair above the temples, which is common in younger persons with Pallister-Killian syndrome, mostly resolves by age five. Additionally, an affected individual's initial lack of muscle tone gives way to fixation of the joints later in life.

Diagnosis

Pallister-Killian syndrome may be suspected from a person's physical features, but a diagnosis requires that a person has the characteristic chromosome abnormality, tetrasomy 12p. PKS is different from many types of chromosomal syndromes in that the causative chromosome abnormality is not found from chromosome studies on the blood. Chromosome testing on skin cells will show the characteristic chromosome abnormality in at least some of the cells. It is believed that the characteristic chromosome abnormality, the isochromosome 12p, does not show up in the blood cells because the abnormal isochromosome is lost in the rapid cell division that creates these blood cells. Diagnosis of Pallister-Killian syndrome has traditionally required a skin biopsy, but recent reports indicate that the diagnosis can be made using cells scraped from the inside the cheek.

Many cases of PKS may be diagnosed prenatally. Pallister-Killian syndrome is detectable by amniocentesis , a routine test offered in pregnancies suspected to be at risk for chromosome problems. Pallister-Killian syndrome may be suspected when certain physical abnormalities are detected on an ultrasound during pregnancy. In pregnancies where Pallister-Killian syndrome has been diagnosed in an unborn baby, many ultrasounds have shown an increased amount of fluid around the baby, in addition to other physical abnormalities, including short arms and legs, heart malformations, diaphragmatic hernia, cystic hygroma, and unusually flat profile of the face.

Treatment and management

There is no treatment or cure for PKS, or for the mental retardation and developmental delays associated with this syndrome. Persons with PKS are treated for the symptoms they display. Individuals with Pallister-Killian syndrome will often take medications for seizures; some may have surgeries due to birth defects involving the diaphragm, intestines, anus, kidneys, genitals, or heart. Physical therapy and occupational therapy may be helpful for development of muscle tone and reduction of joint fixation.

Prognosis

Many infants with PKS die before they are born (in utero) or soon after birth. Some affected individuals reaching their 20s have been reported. Many have severe to profound mental retardation and very few self-care skills. A few reports have described affected persons with milder intellectual impairment.

Resources

BOOKS

Gorlin, Robert J., Michael M. Cohen, and Raoul C. M. Hennekam. "Pallister-Killian Syndrome." In Syndromes of the Head and Neck, 4th edition. New York: Oxford University Press, 2001.

Jones, Kenneth Lyons. "Killian/Teschler-Nicola Syndrome." In Smith's Recognizable Patterns of Human Malformation. Philadelphia: W. B. Saunders, 1997.

PERIODICALS

Genevieve, D., et al. "Mild Phenotype in a 15-year-old Boy with Pallister-Killian Syndrome." American Journal of Medical Genetics 116A(2003): 90–93.

ORGANIZATIONS

National Organization for Rare Disorders (NORD). PO Box 8923, New Fairfield, CT 06812-8923. (203) 746-6518 or (800) 999-6673. Fax: (203) 746-6481. (April 21, 2005.) <http://www.rarediseases.org>.

Pallister-Killian Syndrome Family Support Group. 3700 Wyndale Court, Fort Worth, TX 76109. (817) 927-8854. Fax: (817) 927-2073.

Unique-Rare Chromosome Disorder Support Group. P.O. Box 2189, Caterham, Surrey, CR3 5GN, England. Telephone or fax: (44)(0)1883 330766. Email: info@rarechromo.org. (April 21, 2005.) <http://www.rarechromo.org/>.

WEBSITES

"Pallister-Killian Syndrome." Online Mendelian Inheritance in Man. (April 21, 2005.) <http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601803>.

Judy C. Hawkins, MS, CGC