i(12p)

Pallister-Killian syndrome

 

Epidemiology and Etiology:

    • rare
    • Mosaic form usually
      • Post-zygotic event
    • Tetrasomy for 12p
    • Advanced maternal age is a risk factor
    • Mechanisms:
      • Centromeric misdivision at meiosis I
      • Premeiotic centromere misdivision
      • Nondisjunction at meiosis I
        • Leading to a trisomic zygote
        • Followed by post-mitotic centromeric misdivision
      • Premeiotic nondisjunction
        • Giving rise to a trisomic cell
        • Followed by centromeric misdivision

 

Common sites:

    • Blood is usually negative

 

Gross features:

    • Wide phenotypic variability
    • Facies:
      • “coarse” features
      • Prominent forehead
      • Sparse hair or temporal alopecia
      • Hypertelorism
      • Flat nasal bridge
      • Short nose with anteverted nares
      • macrostomia
      • Short neck
      • Cleft lip / palate
    • Pigmentary dysplasia
      • Streaks of hypo/hyper-pigmentation and facial anomalies
    • Short and broad hands
    • Diaphragmatic hernia
    • Congenital heart defects
    • Anorectal anomalies
    • Genital malformations
    • Supernumerary nipples

 

 

Histologic features:

    •  

 

Immunophenotype:

Marker:

Sensitivity:

Specificity:

 

 

 

 

Molecular features:

    •  

 

Other features:

    • Nearly 100% risk of fetal abnormality
    • variable phenotype, but usually very severe:
      • Prenatal death due to multiple congenital anomalies
      • Severe mental retardation (almost all)
      • Seizures (~60%)
      • Hypotonia (almost all)
    • U/S:
      • Hydramnios
      • Congenital diaphragmatic hernia
      • Micromelia (predominantly rhizomelic type)
      • Less common:
        • Hydrops fetalis
        • Increased nuchal translucency (INT)
        • Hygroma coli
        • Fetal overgrowth
        • Ventriculomegaly
        • Dilation of the cavum pellicidum
        • Absence of stomach visualization
        • Sacral appendix
    • Blood samples negative usually
      • Lymphocyte karyotype is usually normal
      • i(12p) found in skin fibroblasts, amniocytes, and bone marrow cells

 

References:

    • Gardner RJM, Sutherland GR. Chromosome Abnormalities and Genetic Counseling. 2nd ed. Oxford University Press, USA; 1996.
    • Genevieve D et al.  Mild Phenotype in a 15-Year-old boy with Pallister-Killian Syndrome.  Am J Med Genet.  2003;116A:90-93.