Trisomy 14 Mosaicism Including Concomitant Uniparental Disomy: Population Frequency, Cytogenetic Profile, Sex Ratio, Maternal Age, and Obstetric History.

Abstract

Mosaicism for trisomy of chromosome 14 (T14) is a very rare chromosomal disease in liveborn patients. Since the 1970s, when the first patients with mosaicism for T14 were reported, a number of studies on the clinical manifestations of this abnormality have been published. No information on epidemiological parameters was known except for the rarity of the disease and its predominance among female carriers. This was the first systematic review of published cases of mosaic T14 that addressed some epidemiological aspects of this abnormality. We conducted a literature review and collected information on 194 cases of regular T14 and only two cases of mosaic T14 among 21,082 tested spontaneous abortuses. Thus, the rates of nonmosaic T14 and mosaic T14 were 0.9% and 0.09‰, respectively. Additionally, we identified 76 carriers of mosaic T14, diagnosed prenatally and postnatally. Among them, there were 50 carriers of mosaicism for regular T14, 21 carriers of mosaicism due to unbalanced homologous translocation/isochromosome, and five carriers of mosaicism for unbalanced non-homologous Robertsonian translocation involving chromosome 14. The most significant findings were as follows. i) The unexplained fourfold predominance of the carriers of homologous rearrangement relative to non-homologous translocations, but the occurrence of exceptionally rare homologous rearrangements compared to non-homologous translocations in human populations; also, the ratio between these two types of rearrangements (21 and 28, respectively) differed from that in the carriers of non-mosaic UPD(14) (p < 0.005). ii) Female patients were predominant in all studied groups, irrespective of the type of the trisomic line and parental origin of the euploid cell line; there were 19 male and 57 female cases reported. iii) The differences in the maternal age between carriers of mosaicism for regular T14 with and without maternal uniparental disomy were statistically significant (average age of 35.4 and 29.8 years, respectively; p < 0.05). This is intriguing because of the common mechanism of the formation of biparental and uniparental disomy. Additionally, a complicated reproductive history was noted in 25% of the families.

Mosaicism for Autosomal Trisomies: A Comprehensive Analysis of 1266 Published Cases Focusing on Maternal Age and Reproductive History

“…Recent observation of a higher proportion of older mothers in mosaic carriers with concomitant UPD(14) [ 27 ] prompted us to verify this phenomenon on a larger sample of mosaic trisomies. We have identified cases with the largest numbers of known parental origin of diploid cell line and known maternal age.…”

Intussusception in Mosaic Trisomy 14

“…Trisomy 14 is a rare chromosomal disorder associated with a high rate of infant mortality requiring either a mosaic genotype or unbalanced Robertsonian translocation for survival into adulthood. 1 It disproportionately affects females (3:1) with common morphologic features including a broad nose, a short neck, congenital heart disease, growth delay, and developmental delay. [1][2][3] The spectrum of functional status and survival is broad, and the scarcity of data concerning complications and prognosis creates significant challenges in clinical decision-making and offering guidance to patients' families.…”

“…1 It disproportionately affects females (3:1) with common morphologic features including a broad nose, a short neck, congenital heart disease, growth delay, and developmental delay. [1][2][3] The spectrum of functional status and survival is broad, and the scarcity of data concerning complications and prognosis creates significant challenges in clinical decision-making and offering guidance to patients' families. To the best of our knowledge, no previous episodes of intussusception have been reported within the limited available data in this patient population, and we hope this case can better inform care of patients with this rare condition.…”