Korean J Lab Med.  2009 Aug;29(4):366-370. 10.3343/kjlm.2009.29.4.366.

Prenatal Diagnosis of Pallister-Killian Syndrome Associated with Pulmonary Stenosis and Right Ventricular Dilatation

• Park IY
• Shin JC
• Kwon JY
• Koo BK
• Kim M
• Lim J
• Kim Y
• Han K

• KMID: 1096932
• DOI: http://doi.org/10.3343/kjlm.2009.29.4.366

Abstract

Pallister-Killian syndrome (PKS) is a rare disorder characterized cytogenetically by tetrasomy 12p for isochromosome of the short arm of chromosome 12. PKS is diagnosed by prenatal genetic analysis through chorionic villous sampling, genetic amniocentesis, and cordocentesis, or by chromosomal analysis of skin fibroblasts, but is not usually detected by chromosomal analysis of peripheral blood cells. Herein, we report a case of a gravida at 23 weeks gestation with pulmonary stenosis and right ventricular dilation of the heart which were detected by sonography. Fluorescence in situ hybridization and a multicolor banding technique were performed to verify the diagnosis as 47,XX, +mar.ish i(12)(p10)(TEL++)[16]/46,XX[4], and an autopsy confirmed the cardiac anomalies detected on antenatal sonography.

Keyword

Pallister-Killian syndrome; multicolor banding technique; fluorescence in situ hybridization; pulmonary stenosis; right ventricular dilatation

MeSH Terms

Adult
Chromosome Aberrations
Chromosomes, Human, Pair 12
Female
Fetal Diseases/*diagnosis/genetics
Gestational Age
Humans
In Situ Hybridization, Fluorescence
Karyotyping
Pregnancy
*Prenatal Diagnosis
Pulmonary Valve Stenosis/*ultrasonography
Ventricular Dysfunction, Right/*ultrasonography

Figure

• 

  Fig. 1. Conventional cytogenetic analysis on GTG-banded chromosomes from amniotic fluid of the fetus showed 47,XX,+mar in 16 cells and 46,XX in 4 cells.

• 

  Fig. 2. Fluorescence in situ hybridization (FISH) analysis using a TEL/AML1 (LSI TEL/AML1 Dual Color, Extra Signal Fusion Translocation Probe, Abbot Molecular/Vysis, Des Plaines, IL, USA) probe showed two green (TEL) signals located symmetrically on both arms of the marker chromosome (arrows).

• 

  Fig. 3. The chromosome 12-specific mBAND probe kit, XCyte 12 (MetaSystems, Altlussheim, Germany), was hybridized to metaphase cells. Each fluorochrome was detected by adequate filter and the signals were analyzed by Isis/mFISH imaging software (MetaSystems). This analysis refined chromosome regions involved in isochromosome 12. The multiple band pattern confirmed that i(12) contained all regions of 12p.

Reference

1.Pallister PD., Meinsner LF., Elajalde BR., Franche U., Herrmann J., Spranger J, et al. The Pallister mosaic syndrome. Birth Defects. 1977. 12:103–10.

2.Killian W., Teschler-Nicola M. Case report 72: mental retardation, unusual facial appearance, abnormal hair. Synd Ident. 1981. 7:6–7.

3.Langford K., Hodgson S., Seller M., Maxwell D. Pallister-Killian syndrome presenting through nuchal translucency screening for trisomy 21. Prenat Diagn. 2000. 20:670–2.

4.Gilgenkrantz S., Droulle P., Schweitzer M., Foliguet B., Chadefaux B., Lombard M. Mosaic tetrasomy 12p. Clin Genet. 1985. 28:495–502.

5.Chiesa J., Hoffet M., Rousseau O. Pallister-Killian syndrome [i(12p)]: first pre-natal diagnosis using cordocentesis in the second trimester confirmed by in situ hybridization. Clin Genet. 1998. 54:294–302.

6.Schaefer GB., Jochar R., Muneer R., Sangar WG. Clinical variability of tetrasomy12p. Clin Genet. 1997. 51:102–8.

7.Doray B., Girard-Lemaire F., Gasser B., Baldauf JJ., de Gitter B., Spizzo M, et al. Pallister-Killian syndrome: difficulties of prenatal diagnosis. Prenat Diagn. 2002. 22:470–7.

8.Vermeesch JR., Melotte C., Salden I., Riegel M., Trifnov V., Polityko A, et al. Tetrasomy 12pter-12p13.31 in a girl with partial Pallister-Killian syndrome phenotype. Eur J Med Genet. 2005. 48:319–27.

9.Schinzel A. Tetrasomy 12p (Pallister-Killian syndrome). J Med Genet. 1991. 28:122–5.

10.Han JY., Kim TG., Shaffer LG. Detection of the Pallister-Killian syndrome by G-banding and FISH in cultured skin fibroblasts. Korean J Clin Pathol. 1998. 18:284–7. (한진영, 김태겸, Shaffer LG. 배양된 피부 섬유아세포에서 G-banding 과 FISH 로 진단한 Pallister-Killian 증후 군. 대한임상병리학회지 1998;18:284-7.).

11.Lee JS., Kim SH., Choi JA., Nam SY., Kim SY. A case of Pallister-Killian syndrome. J Korean Pediatr Soc. 2000. 43:274–7. (이주석, 김성훈,최정아, 남상욱, 김수영. Pallister-Killian syndrome 1례. 소아과 2000;43:274-7.).

12.Kim MH., Park SY., Kim MY., Lee BY., Lee MH., Ryu HM. Prenatal diagnosis of Pallister-Killian syndrome in two fetuses with increased nuchal translucency. Prenat Diagn. 2008. 28:454–6.

13.Chudoba I., Plesch A., Lörch T., Lemke J., Claussen U., Senger G. High resolution multicolor-banding: a new technique for refined FISH analysis of human chromosomes. Cytogenet Cell Genet. 1999. 84:156–60.

14.Senger G., Ragoussis J., Trowsdale J., Sheer D. Fine mapping of human MHC class II region within chromosome 6p21 and evaluation of probe ordering using fluorescence in situ hybridization. Cytogenet Cell Genet. 1993. 64:49–53.

15.Wenger SL., Steele MW., Yu WD. Risk effect of maternal age in Pallister i(12p) syndrome. Clin Genet. 1998. 34:181–4.

16.Wilson RD., Harrison K., Clarke LA., Yong SL. Tetrasomy 12p (Pallister-Killian syndrome): ultrasound indicators and confirmation by interphase fish. Prenat Diagn. 1994. 14:787–92.

17.Turleau C., Simon-Bouy B., Austruy E., Grisard MC., Lemaire F., Molina-Gomes D, et al. Parental origin and mechanisms of formation of three cases of 12p tetrasomy. Clin Genet. 1996. 50:41–6.

18.Lalatta F., Salmona S., Fogliani R., Rizzuti T., Nicolini U. Prenatal diagnosis of genetic syndromes may be facilitated by serendipitous findings at fetal blood sampling. Prenat Diagn. 1998. 18:834–7.

19.Hoffman JI., Christianson R. Congenital heart disease in a cohort of 19,502 births with long term follow up. Am J Cardiol. 1978. 42:641–7.

20.Wimalasundera RC., Gardiner HM. Congenital heart disease and aneuploidy. Prenat Diagn. 2004. 24:1116–22.

21.Polityko AD., Goncharova E., Shamgina L., Drozdovskaja N., Podleschuk L., Abramchik E, et al. Pallister-Killian syndrome: rapid decrease of isochromosome 12p frequency during amniocyte subculturing. Conclusion for strategy of prenatal cytogenetic diagnostics. J Histochem Cytochem. 2005. 53:361–4.

22.Dufke A., Walczak C., Liehr T., Starke H., Trifonov V., Rubtsov N, et al. Partial tetrasomy 12pter-12p12.3 in a girl with Pallister-Killian syndrome: extraordinary finding of an analphoid, inverted duplicated marker. Eur J Hum Genet. 2001. 9:572–6.

23.Gerdes AM., Hansen LK., Brandrup F., Soegaard K., Christoffersen A., Rasmussen K. Pallister-Killian syndrome: multiband FISH of tetrasomy 12p. Pediatr Dermatol. 2006. 23:378–81.