Skip to content
How It Works
Explore
Resources Ask a Question
Who It's For
Patients
Decode results, prep for appointments, weigh options.
Caregivers & advocates
Carry the research load for someone you love.
Providers & clinicians
Resources for patients in your practice.
Log In Ask a Question
PubMed This is a summary of 11 peer-reviewed journal articles Updated
Genetics

PKS Biology and Diagnostic Testing

At a Glance

Pallister-Killian Syndrome (PKS) is often missed by standard blood tests because the abnormal cells disappear from the blood as a child grows. The most accurate way to confirm a PKS diagnosis is by testing a cheek swab or skin biopsy for the extra isochromosome 12p.

Understanding the biology of Pallister-Killian Syndrome (PKS) is key to making sense of why the diagnosis process is often more complex than standard genetic testing [1]. Because PKS is unique in how it “hides” in certain parts of the body, understanding its biological mechanism can help you better advocate for the right tests and interpret the results.

The Biological Mechanism: Mosaic Tetrasomy 12p

In a typical cell, there are two copies of chromosome 12—one from each parent. PKS is caused by a specific error where a cell has four copies of the short arm (the “p” arm) of chromosome 12 [2][3].

  • Tetrasomy: This means “four bodies.” Instead of the usual two copies of the 12p region, cells with PKS have four [4].
  • Isochromosome 12p [i(12p)]: This is the extra piece of genetic material. It is a “mirror-image” chromosome made of two short arms fused together [4][5].
  • Mosaicism: This is the most critical concept for parents to understand. Mosaic means your child has two different types of cells [6]. Some cells are “typical” (with 46 chromosomes), while others contain the extra isochromosome [1][7].

Why Blood Tests Often Fail

Many families are frustrated by initial “normal” blood tests. This happens because PKS exhibits tissue-specific mosaicism [6][1].
As a child grows, the abnormal cells containing the extra isochromosome tend to disappear from the peripheral blood (circulating blood) but remain in other tissues [1][8]. Because standard blood-based karyotypes or FISH (Fluorescence In Situ Hybridization) tests look at blood cells, they often yield false negatives, meaning they miss the diagnosis entirely [1][5].

The Gold Standard for Testing

To get an accurate diagnosis, doctors must test tissues where the extra chromosome is still present.

  • Buccal Swab (Cheek Swab): This is often the preferred first step because it is non-invasive. Testing cheek cells is much more reliable for PKS than testing blood [9][5].
  • Skin Biopsy: Testing skin cells (fibroblasts) is considered a highly accurate way to confirm PKS, as the extra chromosome is usually stable in these cells [1][5].
  • Array CGH (Chromosomal Microarray): This advanced molecular tool can detect very small amounts of extra genetic material that a standard microscope might miss [9][10].

Interpreting the Genetics Report

A PKS report can be full of intimidating jargon. Here are the most common terms you will see:

Term Simple Explanation
Supernumerary Means “extra” or “above the number” [1].
Marker Chromosome A tiny, unidentified extra chromosome that often turns out to be i(12p) [5].
i(12p) The shorthand for “isochromosome of the short arm of chromosome 12” [2].
De Novo Means the change happened by chance in the child and was not inherited from the parents [2].
Percentage Mosaicism The fraction of cells in that specific sample that had the extra chromosome (e.g., “30% mosaicism”) [11].

What must be on the report: To be certain of a PKS diagnosis, the report should ideally confirm the presence of extra 12p material using a sensitive method like FISH or Microarray on a non-blood sample, such as skin or cheek cells [1][9][5].

For information on how this biology affects the body, read Symptoms and Systemic Involvement in PKS.

Common questions in this guide

Why did my child's blood test come back normal if they have PKS?
Standard blood tests often miss PKS because the condition features tissue-specific mosaicism. As your child grows, the abnormal cells naturally disappear from their circulating blood, which can lead to a false-negative result on standard blood screenings.
What is the most accurate test for diagnosing Pallister-Killian Syndrome?
Because abnormal cells disappear from the blood, doctors must test tissues where the extra chromosome remains stable. A buccal (cheek) swab is the preferred non-invasive first step, while a skin biopsy is considered the highly accurate gold standard for confirming PKS.
What does mosaicism mean on my child's genetic report?
Mosaicism means your child's body contains two different types of cells. Some of their cells have the typical 46 chromosomes, while a percentage of their other cells contain the extra abnormal chromosome that causes PKS.
What is an isochromosome 12p?
Isochromosome 12p, often written as i(12p), is the specific extra piece of genetic material that causes PKS. It is an abnormal, mirror-image chromosome made of two short arms of chromosome 12 fused together.
Does a higher percentage of mosaicism mean my child will have more severe symptoms?
No, the percentage of mosaicism found in a specific tissue sample does not reliably predict your child's future developmental milestones or the overall severity of their condition.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Which specific tissue (blood, skin, or buccal swab) was used for my child's diagnosis, and what percentage of mosaicism was found in that sample?
  2. 2.If the initial blood test was normal but we suspect PKS, which alternative test (like a buccal swab array) should we perform next?
  3. 3.On the genetic report, does my child's result show 'isochromosome 12p' or a different type of chromosomal change?
  4. 4.Can you explain why the percentage of mosaicism in my child's report might not predict their future developmental milestones?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (11)
  1. 1

    Postnatal clinical phenotype of five patients with Pallister-Killian Syndrome (tetrasomy 12p): Interest of array CGH for diagnosis and review of the literature.

    Alqahtani AS, Putoux A, Bonnet Dupeyron MN, et al.

    Molecular genetics & genomic medicine 2019; (7(10)):e00939 doi:10.1002/mgg3.939.

    PMID: 31454185
  2. 2

    Pineocytoma in a child with Pallister-Killian syndrome: a case report and review of the literature.

    De Martino L, Russo C, Bifano D, et al.

    Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery 2024; (40(8)):2619-2623 doi:10.1007/s00381-024-06426-4.

    PMID: 38689102
  3. 3

    A review of structural brain abnormalities in Pallister-Killian syndrome.

    Poulton C, Baynam G, Yates C, et al.

    Molecular genetics & genomic medicine 2018; (6(1)):92-98 doi:10.1002/mgg3.351.

    PMID: 29222831
  4. 4

    Seizures and Cardiomyopathy in a Patient with Pallister-Killian Syndrome due to Hexasomy 12p Mosaicism.

    Toydemir RM, Panza E, Longhurst MC, et al.

    Molecular syndromology 2020; (11(3)):125-129 doi:10.1159/000507598.

    PMID: 32903844
  5. 5

    Pallister-Killian syndrome: Cytogenetics and molecular investigations of mosaic tetrasomy 12p in prenatal chorionic villus and in amniocytes. Strategy of prenatal diagnosis.

    Libotte F, Bizzoco D, Gabrielli I, et al.

    Taiwanese journal of obstetrics & gynecology 2016; (55(6)):863-866 doi:10.1016/j.tjog.2016.07.010.

    PMID: 28040135
  6. 6

    Pallister-Killian syndrome: Review of fetal phenotype.

    Thakur S, Gupta R, Tiwari B, et al.

    Clinical genetics 2019; (95(1)):79-84 doi:10.1111/cge.13381.

    PMID: 29790157
  7. 7

    Fetoplacental cytogenetic discrepancy in a pregnancy with fetal mosaic tetrasomy 12p and Pallister-Killian syndrome detected by amniocentesis.

    Chen CP, Wang LK, Chern SR, et al.

    Taiwanese journal of obstetrics & gynecology 2017; (56(6)):852-856 doi:10.1016/j.tjog.2017.10.034.

    PMID: 29241934
  8. 8

    Using Array-Based Comparative Genomic Hybridization to Diagnose Pallister-Killian Syndrome.

    Lee MN, Lee J, Yu HJ, et al.

    Annals of laboratory medicine 2017; (37(1)):66-70 doi:10.3343/alm.2017.37.1.66.

    PMID: 27834069
  9. 9

    Pallister-Killian Syndrome versus Trisomy 12p-A Clinical Study of 5 New Cases and a Literature Review.

    Arghir A, Popescu R, Resmerita I, et al.

    Genes 2021; (12(6)) doi:10.3390/genes12060811.

    PMID: 34073526
  10. 10

    [Application of single nucleotide polymorphism microarray and fluorescence in situ hybridization analysis for the prenatal diagnosis of a case with Pallister-Killian syndrome].

    Zhang W, Guo Z, Wang W, et al.

    Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 2018; (35(2)):232-235 doi:10.3760/cma.j.issn.1003-9406.2018.02.019.

    PMID: 29652999
  11. 11

    Pallister-Killian Syndrome: The Diagnosis is in the Detail.

    Sailer S, Díaz GA, García MH, et al.

    Klinische Padiatrie 2019; (231(2)):93-95 doi:10.1055/a-0781-2564.

    PMID: 30517961

This guide to PKS genetic testing is for educational purposes only and does not replace professional medical advice. Always consult a pediatric geneticist to interpret your child's specific diagnostic reports.

Get notified when new evidence is published on Pallister-Killian syndrome.

We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.