The pathology of trisomy 13 syndrome

Abstract

Anatomical and histopathological findings in 12 cases of trisomy 13 syndrome (nine with classic full trisomy and three with trisomy 13 and an unbalanced Robertsonian 13/13 translocation) are reported. Emphasis is on the brain defects, cardiovascular anomalies, and histological organ dysplasia. Eight patients showed abnormal development of the forebrain and midline facial structures (holoprosencephaly). Cardiovascular malformations were invariably present, the leading malformation being an infundibular ventricular septal defect often in combination with dextroposition of the aorta and abnormalities of the semilunar valves. Histological abnormalities giving evidence of organ dysplasia were observed in the central nervous system, eyes, pancreas, kidneys, and ovaries. Mild cystic renal dysplasia was a constant feature. Foci of persistent nodular renal blastema were found in six cases. The pancreatic dysplasia appears to be pathognomonic for trisomy 13. These observations illustrate the importance of pathological studies in the recognition of chromosome abnormalities and, more specifically, of trisomy 13 syndrome. Based on autopsy data, trisomy 13 can be diagnosed - or ruled out - with certainty, even in the absence of karyotyping.

Asynchronous replication of alleles in genomes carrying an extra autosome

“…For example, more than 130 different gross abnormalities have been reported in patients with trisomy 18, reviewed by Jones. 18 Secondly, there is a wide overlap between trisomies 13 and 18 in various clinical and pathological features, reviewed by Moerman et al, 19 many of which are also characteristic and diagnostic for trisomy 21. [20][21][22] Third, based on numerous reports, individuals with an extra autosome show, during foetal and neonatal life, a large number of various malignancies compared with the general population, reviewed by Stage and van Den Berghe.…”

“…Evidently, modification in expression of a critical locus in a trisomy is not merely due to its presence in three copies but results also from a non-locus specific effect of the extra autosome on loci which are present in the normal two copies in the genome. The resemblance in congenital brain malformations (holoprosencephaly 19 ) between trisomies 13 and 18 and other syndromes, such as pseudo-trisomy 13, 24 Meckel syndrome, 25 Ivemark syndrome, 26 and hydrolethalus syndrome, 27 all of which show normal karyotypes, may also point to the possibility that the congenital brain anomalies associated with autosomal trisomies are not necessarily caused by triplicate dosage of susceptible genes.…”

“…[18][19][20][21][22][23][24] The reasons for this variation are unknown. Presumably, this variation may be accounted for in part by a locus non-specific shift in the expression mode of many loci, not present on the extra chromosome, from a biallelic to a monoallelic mode of expression.…”

A case of trisomy 21 with holoprosencephaly: The fifth case

“…About two-thirds of the cases of holoprosencephaly show chromosomal abnormalities (Moerman et aL, 1988). Structural and Vol.…”

Medical and Ethical Considerations Related to Viable Fetus with Trisomy 13 in the 36th Week of Pregnancy – a Review of the Literature

“…Other authors estimate that 17-39% of patients with trisomy 13 have HPE [36], these lower estimates are the result of prenatal diagnosis by USG. Pathologic examination, which is the most objective, shows that as many as 67% of patients with trisomy 13 have signs of forebrain anomalies consistent with HPE [37]. The most common clinical features of trisomy 13 include mental and growth retardation, craniofacial dysmorphisms, hand and foot anomalies, brain, heart and kidney defects, which are also found in carriers of 13q partial deletion [32].…”