What is Pallister-Killian syndrome?

Pallister-Killian syndrome (PKS) is an extremely rare genetic disorder that is present at birth. The prevalence has been estimated to be 1 in 20,000; however, it is likely that PKS is underdiagnosed due to the difficulty of making a cytogenetic diagnosis from a blood test.

The signs and symptoms of Pallister-Killian syndrome vary from child to child and range in severity. Typically, children with this diagnosis have extremely weak muscle tone (hypotonia), intellectual impairment and developmental delays, distinct facial features, skin pigmentation differences, seizures, and other birth defects.

Additionally, babies with Pallister-Killian syndrome often experience a variety of developmental complications related to weak muscle tone, including:

• Breathing and feeding difficulties
• Delays in gross motor skills such as sitting, standing, and walking
• Developmental and speech delays

Pallister-Killian syndrome is also known as isochromosome 12p syndrome, tetrasomy 12p mosaicism, Pallister-Killian mosaic syndrome, and PKS.

Cause

Pallister-Killian syndrome is a chromosomal disorder caused by having an extra chromosome. It is not inherited and occurs spontaneously in a child by chance. All cases recorded to date have been sporadic.

Humans normally have 46 chromosomes, 23 inherited from each parent. A child with Pallister-Killian syndrome has 47 chromosomes. This extra chromosome is made up of two copies of the short arm (p arm) of chromosome 12 in some cells of the body. In these cells, there are four copies of this 12p arm of chromosome 12, instead of the usual two copies. This is called tetrasomy 12p.

PKS is a mosaic syndrome, meaning that an individual has the extra chromosomal material in some cells of the body, but not all. This extra genetic material creates the distinctive characteristics of Pallister-Killian syndrome.

Signs and symptoms

The symptoms of Pallister-Killian syndrome can vary, but generally include many of the following:

• Extremely weak muscle tone, especially in infancy and early childhood
• Distinctive facial features:  
• Large forehead that is often broad
• Depressed nasal bridge
• Widely-spaced eyes (orbital hypertelorism), which may include droopy eyelids (ptosis)
• Low-set ears with thickened helices (top rim of the ear)
• Cupid’s bow lip with the extension of the phitral skin into the vermilion border (termed Pallister lip)
• Highly arched or cleft palate
• Thin hair on the head and sparse eyebrows
• Intellectual disabilities
• Developmental and speech delays
• Skin pigmentation differences, such as streaks or patches of skin that are lighter or darker than surrounding skin
• Skeletal differences
• Extra fingers and toes (polydactyly)
• Hip dislocation
• Joints that are stiff or will not move (contractures)
• Heart defects
• Seizures
• Congenital diaphragmatic hernia
• Hearing and vision problems
• Lung and breathing difficulties
• Abnormalities of the genitals and genitourinary system

Testing and diagnosis

Diagnostic evaluation begins with a thorough medical history and physical examination of your child. At The Children’s Hospital of Philadelphia, clinical experts use a variety of diagnostic tests to diagnose Pallister-Killian syndrome, including:

• Chromosome study of the blood: Clinicians study blood samples to detect chromosome abnormalities, such as additional or missing genetic material. However, individuals with mosaic tetrasomy 12p often have normal chromosomes in their blood cells; therefore, testing a different tissue type such as skin may be required to confirm the diagnosis.
• Chromosome study of skin cells (fibroblasts): Clinicians test multiple areas of the skin and compare the genetic material. If clinicians suspect your child has Pallister-Killian mosaic syndrome, they will likely use this test to confirm the diagnosis. Clinicians prefer the skin cell test, rather than the blood test, because it identifies mosaic conditions when not all cells are affected.
• Fluorescent in situ hybridization (FISH): During this highly accurate diagnostic blood test, clinicians map the genetic material in a child’s cells. The FISH test was pioneered at CHOP and allows clinicians to see which chromosomes have additional or missing genetic material.

Additional imaging tests, such as X-rays, MRIs, CT scans, and ultrasounds, may be done to address specific areas of concern for your child.

Pallister-Killian syndrome can also be diagnosed before birth by amniocentesis or chorionic villus sampling (CVS). These tests involve removing a small amount of amniotic fluid that surrounds a baby in the womb, or a sample of chorionic villi, tissue from the placenta which has cells from the baby.

Treatment

Currently, there is no cure for Pallister-Killian syndrome. Treatments offered to children with the condition can help manage each child’s specific symptoms and developmental needs. The goal of all these options is to help children with Pallister-Killian mosaic syndrome live as normal a life as possible and maximize their potential.

Depending on your child’s set of symptoms, treatment options may include:

• Surgery to address medical conditions such as congenital diaphragmatic hernia, heart anomalies, genitourinary conditions, and cleft palate.
• Respiratory and breathing support, especially for younger children with weak muscle tone.
• Physical, occupational, and recreational therapy to build muscle mass and address fine and gross motor skills.
• Enrollment in early intervention programs to address developmental delays, intellectual differences, and issues with communication (such as speech, hearing, and vision problems).
• Assisted communication devices and sign language training. Most children with Pallister-Killian mosaic syndrome speak later than other children and may develop only limited vocabulary throughout their lives.
• Bracing, casting, or surgery to address bone issues. Some children with Pallister-Killian may develop a spine curvature (scoliosis or kyphosis) during childhood.
• Appropriate management of seizures, if present.

Long-term outcomes

Children with Pallister-Killian syndrome will require coordinated, life-long medical care. Some babies born with the disorder also face life-threatening birth defects in infancy and may not survive early childhood.

Most children will have learning difficulties and attend special schools where they can receive individualized instruction. Some — with milder forms of the disorder — can be educated in mainstream schools with the help of dedicated teachers and support workers.

In adulthood, many individuals with Pallister-Killian syndrome will remain dependent on parents and family members. There are some adults with milder forms of the condition who are able to have jobs and live more independent lives at home or in a group-home setting. Ongoing support, encouragement, and monitoring will be needed.

Research

The Center for Cornelia de Lange Syndrome and Related Diagnoses at CHOP continues to research Pallister-Killian syndrome with a focus on both molecular and cellular studies, as well as clinical studies. Several of our current projects include:

• A delineation of a 12p critical region in PKS
• Identification of downstream effects of the genes on 12p by genome-wide expression in PKS

Our research team also continues to collect clinical information to better understand the natural history and phenotype characterization of PKS. Our research is supported by The Children’s Hospital of Philadelphia and the PKS Kids Foundation.