Variegated aneuploidy related to premature centromere division (PCD)

2000-11-01   Alberto Plaja 

Unitat de Genötica, Hospital Materno- Infantil Vall dHebron Pg. Vall dHebron 119- 129, 08035- Barcelona, Spain

Identity

Name

Variegated aneuploidy related to premature centromere division (PCD)

Note

  • the term premature centromere division has also been utilized to describe an unrelated cytogenetic phenomenon, the age related loss of centromeric function in chromosome X , 
  • variegated aneuploidy has also been described in patients without PCD and patients with Roberts syndrome
  • Inheritance

  • only 11 patients known , 
  • premature centromere division (PCD) without variegated aneuploidy has been shown to have an autosomal dominant inheritance, with an estimated frequency of 0.1% of the population , 
  • it has been proposed that patients with variegated aneuploidy related to PCD are homozygotes for this trait, but in several cases one of the parents do not show elevated frequency of PCD , 
  • a recessive inheritance with hormonal factors modifying the expression of PCD in a carrier, isodisomy of one chromosome or loss of heterozygosity has been suggested
  • Omim

    257300 , 614114

    Mesh

    C536987

    Orphanet

    1052 Mosaic variegated aneuploidy syndrome

    Umls

    C1850343

    Clinics

    Note

    patients show a remarkably constant clinical phenotype probably due to high cellular mortality induced by the aneuploidies; similar clinical findings have also been found in other patients with an expected increased cellular mortality (variegated aneuploidy without PCD and the \"ring syndrome\")

    Phenotype and clinics

    the clinical phenotype of the 11 patients described in the literature includes microcephaly (11\/11), central nervous system (CNS) anomalies (5\/6) with cerebellar defects and migration defects, mental retardation (8\/9), prenatal (always noted over 23 weeks of gestation) and postnatal growth retardation (10\/10), flat and broad nasal bridge (4\/7), apparently low-set ears (5\/8), eye abnormalities (8\/10), skin abnormalities (3\/9) and ambiguous genitalia in male patients (4\/6); seizures have been reported in 5 patients; cancer is a major concern in the clinical management of these patients (5\/11); birth weight corrected for gestational age ranges from -1.3 to -4.1 SD, birth length from -0.8 to -5.4 SD and OFC from -2.6 to -5.8

    Neoplastic risk

    the occurrence of Wilms tumor in three patients, rhabdomyosarcoma in two others and acute leukemia in a fifth characterizes this condition as a chromosome instability disorder with a high risk of malignancy; interestingly enough, preferential loss of maternal 11p15.5 chromosome region has been repeatedly reported in Wilms tumor as well as in rhabdomyosarcoma

    Prognosis

    although published data is incomplete, at least 4 patients have died before 2 years of age, a fifth deceased at 42 years and one patient aged 18 month has an advanced, relapsed rhabdomyosarcoma; patients death had been related to pneumonia (one patient), leukemia (one patient), and Wilms tumor (three cases)

    Cytogenetics

    Inborn condition

    Atlas Image
    cell showing premature centromere division (PCD) phenomenon, with split centromeres and splayed chromatids in all the chromosomes

    Cancer cytog

    cytogenetic analysis of one embryonal rhabdosarcoma showed normal karyotype in cultured cells and extensive aneuploidy with some estructural aberrations in the only two cells obtained from direct harvest

    Bibliography

    Pubmed IDLast YearTitleAuthors
    32766151988C-anaphases in lymphocyte cultures versus premature centromere division syndromes.Chamla Y et al
    14665711992C-anaphases: a mitotic variant.Domínguez MG et al
    37803181986Premature centromere division dominantly inherited in a subfertile family.Gabarrón J et al
    96770591998Mosaic variegated aneuploidy with multiple congenital abnormalities: homozygosity for total premature chromatid separation trait.Kajii T et al
    104293591999Syndrome of microcephaly, Dandy-Walker malformation, and Wilms tumor caused by mosaic variegated aneuploidy with premature centromere division (PCD): report of a new case and review of the literature.Kawame H et al
    38178121987Does "ring syndrome" exist? An analysis of 207 case reports on patients with a ring autosome.Kosztolányi G et al
    99168371999Child with mosaic variegated aneuploidy and embryonal rhabdomyosarcoma.Limwongse C et al
    36538921987Premature centromere division (PCD): a dominantly inherited cytogenetic anomaly.Madan K et al
    108779822000Chromosomal instability syndrome of total premature chromatid separation with mosaic variegated aneuploidy is defective in mitotic-spindle checkpoint.Matsuura S et al
    23074591990Mitotic disturbance associated with mosaic aneuploidies.Miller K et al
    111695582001Variegated aneuploidy related to premature centromere division (PCD) is expressed in vivo and is a cancer-prone disease.Plaja A et al
    18092391991Mosaic variegated aneuploidy with microcephaly: a new human mitotic mutant?Warburton D et al