Pallister-Killian syndrome

Pallister-Killian syndrome (PKS), also known as tetrasomy 12p mosaicism or isochromosome 12p syndrome, is a rare chromosomal disorder caused by the presence of an extra isochromosome composed of two copies of the short arm of chromosome 12 (i(12p)). This supernumerary isochromosome is typically present in a mosaic pattern, meaning it is found in some cells but not others. The condition is not inherited but arises as a sporadic event during cell division, most often during maternal meiosis. Because the abnormal chromosome is preferentially lost from blood lymphocytes, diagnosis often requires analysis of skin fibroblasts or buccal mucosal cells rather than standard blood karyotyping, though chromosomal microarray on blood can detect the gain of 12p material. PKS affects multiple body systems. Key clinical features include characteristic facial features (high forehead, sparse anterior scalp hair in infancy, broad flat nasal bridge, wide mouth with a thin upper lip, and a long philtrum), profound to severe intellectual disability, seizures (often infantile spasms), hypotonia (markedly reduced muscle tone from birth), and streaks of skin hypopigmentation or hyperpigmentation following the lines of Blaschko. Congenital anomalies are common and may include diaphragmatic hernia, congenital heart defects, renal anomalies, and supernumerary nipples. Many affected individuals have limited or absent speech development and significant motor delays. Hearing loss and vision problems may also occur. There is no cure for Pallister-Killian syndrome, and management is supportive and multidisciplinary. Treatment focuses on addressing individual symptoms: antiepileptic medications for seizures, physical and occupational therapy for motor delays, speech therapy, and surgical correction of congenital anomalies such as diaphragmatic hernia or cardiac defects when needed. Early intervention programs are recommended to optimize developmental outcomes. Life expectancy is variable; some individuals with severe congenital malformations may have a shortened lifespan, while others survive into adulthood with significant support needs.

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