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Clinical Vignette
Antenatal ultrasonography features | Huang et al., 2012 | Pallister Killian Syndrome | Fetus described in our study |
Polyhydramnios | + | + | - |
Short long bones | + | + | + |
Increased nuchal translucency | + | + | - |
Congenital diaphragmatic hernia | - | + | - |
Cardiac anomaly | - | + | - |
Polydactyly | - | + | - |
Fetal growth restriction |
|
| - |
Features | Pallister Killian syndrome | Huang et al., 2012 | Fetus reported in our study |
Brachycephaly | + | + | + |
Round face | - | + |
|
Coarse facies | + | - | +, mild |
Flat facial profile | + | + | + |
Broad nasal bridge | + | + | + |
Anteverted nostril | + | + | + |
Long Philtrum | + | + | + |
Upper Lips | Thin | Thick | Thin |
Short Neck | + | + | + |
Hung et al. reported a fetus with trisomy 12p at 30 weeks in a primigravida (Hung et al.,2012). Ultrasonography features included polyhydramnios, short lone bones and abnormal spine curvature. Fetal facial dysmorphism included hypertelorism, marked prenasal thickness, broad and flat nasal bridge, cleft palate, large philtrum with thickened everted upper lip, and micrognathia.
Doray et al. stated that the three most frequent ultrasound indicators were polyhydramnios (84%), congenital diaphragmatic hernia (CDH) (16%) and micromelia of predominantly rhizomelic type (10%) (Doray et al., 2002).
The fetus we described also had short long bones but there was no polyhydramnios probably because of the early gestation at detection. Left tibia was small and deformed. Histopathology of bone showed localized dysostosis. Oligonucleotide-based aCGH showed a 35.4 MB duplication of 12p [arr 12p13.33p11.1 (0–35,400,000) × 3] in the case reported by Hung et al. Our case had duplication of 18.1 MB at cytoband 12p13.33p12.1. Izumi et al. described a minimal critical region for Pallister Killian Syndrome phenotype in a case with duplication of 26 genes (Izumi et al.,2014). Three genes, ING4, CHD4, and MAGP2 represent strong candidate genes for minimal critical region of this phenotype. ING4 gene plays important role in transcriptional regulation and CHD4 gene is involved in chromatin remodelling, DNA damage response and cell cycle control.
This case highlights the importance of a well-performed antenatal ultrasound. Down syndrome may be the commonest chromosomal abnormality but a low risk on the combined first trimester screening does not exclude other abnormalities. Another point to be emphasized is that any structural abnormality warrants microarray over conventional karyotyping. A complete postnatal evaluation including infantogram and fetal autopsy is essential to confirm ultrasound findings and to establish the diagnosis, which is instrumental in assigning appropriate recurrence risk.
Our report further expands the spectrum of antenatal and postnatal phenotype of trisomy 12p.
1. Doray B, et al. Pallister-Killian syndrome: difficulties of prenatal diagnosis. Prenat Diagn 2002; 22(6):470-477.
2. Hung CC, et al. Prenatal diagnosis of a fetus with a de novo trisomy 12p by array-comparative genomic hybridization (array-CGH). Gene 2012; 595: 178-182.
3. Izumi K, et al. Pallister–Killian syndrome. Am J Med Genet Part C Semin Med Genet 2014; 166C: 406-413.
4. Rauch A, et al. Clinical and molecular cytogenetic observations in three cases of “trisomy 12p syndrome”. Am. J. Med. Genet 1996; 63, 243-249.
5. Segel R, et al. The natural history of trisomy 12p. Am J Med Genet 2006; 140: 695-703.
6. Tekin M, et al. De novo inverted tandem duplication of the short arm of chromosome 12 in a patient with microblepharon. Am J Med Genet 2001; 104: 42-46.
7. Tsai AC, et al. De novo duplication of the short arm of chromosome 12: dup(12)(p13.1p13.3). Am J Med Genet A 2005; 134A: 229-230.
8. Uchida IA et al. Identification of partial 12 trisomy by quinacrine fluorescence. J Pediatr 1973;82: 269-272.
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