Isochromosome 12p mosaicism (Pallister mosaic aneuploidy or Pallister‐Killian syndrome): Report of 11 cases

Abstract

We report on 11 cases of isochromosome 12p mosaicism (or Pallister mosaic aneuploidy syndrome) in which the isochromosome is usually absent in cultured lymphocytes but present in fibroblasts. The patients range in age from a 22-week-gestation fetus to a 45-year-old man. They have a distinct pattern of anomalies which enables one to make a diagnosis based on clinical manifestations alone. Craniofacial manifestations include "coarse" face with prominent forehead, sparsity of scalp hair, hypertelorism, epicanthal folds, flat bridge of nose, and highly arched palate. Affected newborn infants are profoundly hypotonic with sparsity of scalp hair especially bitemporally and a prominent forehead. Most have accessory nipples. Birthweight and growth parameters are usually normal; however, some newborn infants are unusually large. In infancy, the facial appearance becomes "coarse," hypotonia persists, and seizures may occur. As adults, growth may be normal, scalp hair is thicker and the mandible becomes prominent. Most have a generalized pigmentary dysplasia which may be evident with a Wood's lamp only. All cases have been sporadic and there is no consistent pattern of advanced parental age.

Partial tetrasomy 12pter-12p12.3 in a girl with Pallister-Killian syndrome: extraordinary finding of an analphoid, inverted duplicated marker

“…The distinct phenotype of PKS enables a diagnosis based solely on clinical manifestations in the majority of cases. 3,7 In our patient, the clinical findings were consistent with PKS. Nevertheless, cytogenetic analysis did not reveal the typical finding of supernumerary i(12p) in fibroblasts.…”

Pallister-Killian syndrome: Cytogenetic and biochemical studies

“…In a number of cases (Lopes et al, 1985;Raffel et al, 1986;Pauli et aI., 1987;Reynolds et al, 1987;Warburton et al, 1987), i(12p) was found in 10-20~ of blood lymphocytes. The percentage of tetrasomy 12p in lymphocytes in our case (43~) was even higher.…”

“…It should be noted that tetrasomy 12p mosaicism has been increasingly ascertained at birth or by prenatal diagnosis. Review of autopsy findings in 8 such cases (Gilgenkrantz et aI., 1985;Lopes et al, 1985;Hiraishi et aI., 1987;Pauli et al, 1987;Reynolds et al, 1987;Steinbach and Rehder, 1987;Warburton et al, 1987) showed that internal malformations are not at all rare and lung hypoplasia is a common pathological finding (Table 4). This type of malformation may explain why neonatal asphyxia is frequently associated with Pallister-Killian syndrome.…”

“…The similarity of banding patterns between the 12p and 21q has sometimes led to a misinterpretation of i(12p) as i(21q) (Fryns et al, 1982;Hunter et al, 1982;Kwee et aI., 1984;Lopes et al, 1985). More than two dozen of cases have so far been reported (Reynolds et al, 1987). Patients with Pallister-Killian syndrome invariably show characteristic clinical features, including normal intrauterine growth, severe mental retardation, pigmentary dysplasia, aberrant scalp hair pattern in infancy and coarse face (Buyse and Korf, 1983).…”

Pallister‐Killian syndrome detected by fluorescence in situ hybridization

“…This syndrome (also known as Pallister mosaic aneuploidy syndrome or isochromosome 12p mosaicism) is characterized by postnatal growth retardation, seizures, hypotonia, deafness, profound mental retardation, minimal speech development, and a distinctive facial appearance (high prominent forehead, ocular hypertelorism, sparse anterior scalp hair, prominent lower lip, large ears with thick protruding lobules, cupid-bow shaped upper lip, and a long philtrum) [Pallister et al, 1977;Teschler-Nicola and Killian, 1981;Reynolds et al, 1987;Bergoffen et al, 1993]. A chromosome 12 abnormality (tetrasomy 12p) has been reported in skin biopsies from these patients but this chromosome anomaly is usually not found (or in only a small proportion, e.g., <0.5%, of blood cells) in peripheral blood [Raffel et al, 1986;Warburton et al, 1987;Larramendy et al, 1993;Ohashi et al, 1993].…”