Pallister–Killian Syndrome (PKS) is also known as Tetrasomy 12p, Isochromosome 12p, or Killian–Teschler Syndrome.

PKS is a condition caused by alterations in the cellular genetic makeup, specifically by duplication of a segment of chromosome 12. The term “genetic” therefore refers solely to the presence of this anomaly in the DNA, and does not imply heritability.

No, PKS is not hereditary. The anomaly is defined de novo, meaning it cannot be transmitted by the parents, and has a sporadic onset, i.e., it occurs randomly.

To date, the cause remains unknown. However, it is understood that it is not hereditary, environmental, or related to maternal exposure to harmful substances.

Genetic mosaicism refers to the coexistence of two or more cell lines with different chromosomal makeups within the same individual. In practice, while some cells retain the typical chromosomal complement, others carry the tetrasomy 12p anomaly.

PKS is also known as tetrasomy 12p, since the anomaly affects chromosome 12. This chromosome consists of a short arm (p) and a long arm (q), but in the isochromosome 12p the short‐arm segment is duplicated, creating an atypical genetic arrangement.

As a result, affected cells exhibit four copies of the 12p short arm (tetrasomy 12p) instead of the normal two copies, with clear clinical phenotype implications.

Yes, PKS is an aneuploidy, meaning an alteration in chromosome number where one cell line has 47 chromosomes instead of 46. The resulting karyotype is therefore:

• Female: 46,XX / 47,XX,+i(12p)
• Male: 46,XY / 47,XY,+i(12p)

The true incidence of PKS is not precisely known, but it is estimated at about 1 in 25,000 live births. To date, around 500 cases have been documented worldwide, of which approximately 50 are in Italy (2025 data).

The high proportion of diagnoses in Italy is due to several factors:

• Universal access to the National Health Service, making specialist consultations available to everyone;
• Training and awareness among Italian physicians, enhanced by the Association’s and its experts’ efforts;
• The ability to recognize the syndrome even in milder cases and at a very early age, whereas in other countries often only the most severe cases are diagnosed.

In the absence of a national (which the Association is working on) and a global registry, the data remain approximate. Clinicians estimate that in the United States alone there may be over 2,000 individuals with PKS who are still undiagnosed.

To date, there is no definitive cure for PKS. However, supportive therapies tailored to the severity of each clinical presentation are available, aimed at promoting psychomotor development and the acquisition of functional skills.

It is also crucial to schedule regular follow-up appointments with specialists experienced in this condition, to monitor progression and adjust the treatment plan promptly.

In addition to the team of doctors at the Children’s Hospital of Philadelphia (USA), led by Dr. Ian Krantz, who conduct genetic research on PKS, the group of specialists at PKS Italia – including Prof. Duccio Maria Cordelli, Head of Child Neuropsychiatry at the S. Orsola Malpighi University Hospital in Bologna – carry out significant studies in the neurological, behavioral, and genetic fields.

The American and Italian teams collaborate in synergy, combining effort and hope, with the goal of one day developing a truly effective gene therapy for Pallister–Killian Syndrome.

Diagnosis is challenging due to the tissue-specific mosaic distribution of isochromosome 12p. During pregnancy, it is only possible in certain cases: when fetal malformations are particularly striking, a morphological ultrasound may prompt the obstetrician to pursue in-depth genetic testing, sometimes revealing tetrasomy 12p.

A 3D morphological ultrasound can sometimes highlight the craniofacial features typical of newborns with PKS. In other cases, invasive cytogenetic tests (chorionic villus sampling or amniocentesis) can identify the chromosomal anomaly.

However, these tests often yield an false negative result because the sample may not contain cells with the defect. Peripheral blood lymphocyte analysis is also frequently inconclusive: blood cells regenerate rapidly, and newly formed cells may not carry the tetrasomy.

The most reliable diagnostic technique today is Array CGH performed on a skin biopsy to collect fibroblasts; interphase FISH on skin samples or buccal swabs is also highly effective.