Pallister–Killian syndrome caused by mosaicism for a supernumerary ring chromosome 12p

Abstract

Pallister-Killian syndrome (PKS) is a rare but distinctive chromosomal syndrome distinguished by severe intellectual impairment, characteristic facial features, and variable structural anomalies. The characteristic cytogenetic abnormality in PKS is a supernumerary isochromosome 12p that confers mosaic tetrasomy. We describe a female child with PKS in whom tetrasomy 12p resulted from a supernumerary ring chromosome containing two copies of chromosome 12cen --> p13, a novel cytogenetic finding. The ring chromosome exhibited tissue-limited mosaicism, being absent in blood but detected in 38% of buccal mucosa cells and 41% of skin fibroblasts. Our patient demonstrated the typical dysmorphic characteristics of PKS, but her development was relatively advanced in comparison to children with isochromosome PKS. Her milder developmental phenotype may be attributable to differences in the mosaic distribution or the genomic content of the ring chromosome compared to mosaic isochromosome 12p.

Supernumerary Ring Chromosome: An Etiology for Pallister-Killian Syndrome?

“…This prenatal case confirms the postnatal finding of Yeung et al [9] that ring chromosome 12p can be one of several and more common, cytogenetic abnormalities causing PKS. However, the recurrence of ring chromosomes as a cause of PKS might be underestimated because of the technical difficulties related to its characterizations before the advent of aCGH technology.…”

“…Although the most frequent abnormality is a supernumerary isochromosome of the short arm of chromosome 12, different variants have been reported such as coexisting trisomy 12p and tetrasomy 12p [8], ring of tetrasomy 12p [9] and an inverted duplicated 12p with a neocentromere [10]. …”

Pallister-Killian syndrome

“…It is caused by supernumerary isochromosome 12p (tetrasomy 12p) [1,2]. PKS was first described in 1977 by Pallister in adults [3], and later in 1981 by Killian and Teschler Nicola in children with mental retardation, severe dysmorphic features, and skin changes [4].…”

Mosaic Intrachromosomal Triplication of (12)(p11.2p13) in a Patient with Pallister-Killian Syndrome

“…The karyotype in the cultured blood lymphocytes is normal in most cases, but one supernumerary isochromosome 12p is present in high percentage in cultured skin fibroblasts and bone marrow cells of the patients [3]. Supernumerary analphoid inverted duplicated chromosome 12p and a supernumerary ring chromosome consisting of two copies of chromosome 12p have also been reported in the rare cases with PKS [4,5]. Clinical features of this syndrome include; mental retardation, pigmentary skin abnormalities, seizures, prominent forehead with temporal balding, hypertelorism, short nose, short neck, flat nasal bridge, flat occiput and macrosomia [6,7].…”