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Key Points

  • Characterized by tissue-specific presence of an abnormal extra chromosome, which consists of two copies of the short arm of chromosome 12.

  • Abnormal (marker) chromosome is more likely to be found in amniocytes or fibroblasts than blood.

  • Associated with advanced maternal age.

  • Sonographic findings: polyhydramnios, diaphragmatic hernia, rhizomelic short limbs.

  • Main consideration in differential diagnosis is Fryns syndrome.

  • Very poor long-term prognosis. All survivors are mentally retarded.

  • Sporadic inheritance.


Tetrasomy 12p is a multiple congenital anomaly syndrome characterized by the tissue-specific presence of a marker chromosome in fibroblasts, but not lymphocytes, of affected patients. The clinical symptoms associated with this condition were first recognized in 1977, when Pallister described two adults, aged 19 and 37, who had profound retardation, severe hypotonia, coarse facial features, and pigmentary abnormalities. Both of these patients had an extra chromosome that was identified as a probable isochromosome of the short arm of chromosome 12 (Pallister, 1977). Independently, Teschler-Nicola and Killian (1981) reported a 3-year-old with severe mental retardation, dysmorphic facies, and sparse, dystrophic hair. Buyse and Korf (1983) were the first to suggest that these two seemingly disparate clinical presentations actually represented different manifestations of the same syndrome. The discrepancy between the two was explained by the fact that the isochromosome 12p was demonstrable in fibroblasts but not lymphocytes from affected patients. The interesting and unique aspect of this syndrome is that mosaicism exists for the chromosomal abnormality, and diagnosis usually depends on performing a chromosome analysis on amniocytes or fibroblasts from a skin biopsy.

From the prenatal perspective, tetrasomy 12p is usually diagnosed in one of two ways: either it is a karyotype abnormality found at amniocentesis performed for advanced maternal age (32% of cases) or it is detected when karyotyping is performed because fetal anomalies have been detected on sonography (52% of cases) (Wilson et al., 1994; Doray et al., 2002). Advanced maternal age is known to be a risk factor for the development of the isochromosome 12p. In a review of 30 case reports of Pallister–Killian syndrome, Wenger et al. (1988) found that the average age of the mothers of affected patients was 30 years. It is currently thought that there is an initial nondisjunctional event that results in trisomy 12. This is then followed by a centromeric misdivision at meiosis I or II (Struthers et al., 1999). The abnormal extra isochromosome is progressively lost in vivo during embryogenesis and in vitro during tissue culture. This hypothesis has been proven in several cases using molecular markers (Cormier-Daire et al., 1998; de Ravel et al., 2004).

The diagnosis of tetrasomy 12p is made by karyotype (Figure 138-1). The extra chromosome in this syndrome was originally thought to be derived from the long arm of chromosome 21 based on similarities in the cytogenetic banding patterns between ...

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