Pallister-Killian Syndrome, PKS, is a rare and complex genetic disorder. It affects multiple systems within the body, leading to a wide range of developmental and physical challenges.
Understanding Pallister-Killian Syndrome
Pallister-Killian Syndrome is classified as a multisystem developmental disorder. It impacts various parts of the body, including the brain, face, heart, and skeleton. As a rare disease, PKS has an estimated prevalence of fewer than 1 in 20,000 live births, though the exact number may be higher due to underdiagnosis.
The Genetic Basis
Pallister-Killian Syndrome arises from tetrasomy 12p, a genetic alteration where affected individuals have an extra copy of the short arm of chromosome 12 (12p). This extra genetic material typically appears as an isochromosome, which is a chromosome with two identical arms, formed when the centromere divides horizontally instead of vertically.
The condition is also mosaic, meaning the extra isochromosome 12p is not present in all cells of the body. Some cells will have the genetic change, while others will have a typical chromosome makeup. This mosaicism contributes to the variability in symptoms and severity observed among individuals with PKS. The genetic change is almost always sporadic, meaning it occurs spontaneously during the formation of reproductive cells or early fetal development, rather than being inherited from a parent.
Recognizing the Characteristics
Individuals with Pallister-Killian Syndrome often present with a recognizable set of physical features. Distinct facial characteristics frequently include a high, prominent forehead, sparse hair on the temples, a broad nasal bridge, and widely spaced eyes.
Developmental delays are a consistent finding, with severe intellectual disability being typical. Motor skills are significantly affected, often leading to challenges with sitting, crawling, and walking. Many individuals experience hypotonia, or low muscle tone, which contributes to feeding difficulties and delayed motor milestones.
Skeletal abnormalities, such as contractures of the large joints, are frequently observed. Skin pigmentation changes, specifically areas of hypopigmentation or hyperpigmentation, may also be present. Internal organ involvement can include congenital heart defects, kidney abnormalities, and diaphragmatic hernias, where abdominal organs protrude into the chest cavity. Seizures are also a common neurological complication.
Diagnosis
The diagnosis of Pallister-Killian Syndrome often begins with a suspicion based on the presence of characteristic clinical features. However, definitive confirmation requires specific genetic testing. Karyotyping, a test that examines the number and structure of chromosomes, can identify the extra isochromosome 12p, especially when performed on skin fibroblast cells, as the mosaicism might not be easily detected in blood cells.
Fluorescence In Situ Hybridization (FISH) is another targeted genetic test that uses fluorescent probes to highlight the specific region of chromosome 12p, confirming its duplication. Chromosomal microarray analysis provides a more detailed look at the entire genome, detecting duplications and deletions that might be missed by traditional karyotyping. Early diagnosis is important for initiating early intervention services and appropriate medical management.
Supportive Care and Prognosis
Management of Pallister-Killian Syndrome involves a multidisciplinary approach to supportive care, as there is no cure for the underlying genetic condition. Therapeutic interventions are tailored to address individual needs, including physical therapy to improve motor skills and muscle strength, occupational therapy to enhance daily living activities, and speech therapy to support communication development. Early intervention programs are particularly beneficial in promoting developmental progress.
Medical complications require ongoing monitoring and management. Seizures are often managed with anti-epileptic medications. Feeding difficulties, common due to low muscle tone, may necessitate specialized feeding techniques or even gastrostomy tube placement to ensure adequate nutrition. Regular screenings for hearing and vision impairments are also performed, with interventions such as hearing aids or corrective lenses provided as needed.
The prognosis for individuals with PKS varies widely depending on the severity of their symptoms and associated medical complications. While life expectancy can be reduced, supportive care aims to maximize the quality of life for individuals and their families, focusing on comfort, developmental support, and comprehensive medical attention.
Citations
https://www.ncbi.nlm.nih.gov/books/NBK1137/