Homozygous Robertsonian translocations in a fetus with 44 chromosomes

Abstract

We report the unique finding of a human fetus with 44 chromosomes with homozygous 14;21 translocations. This fetus appeared phenotypically normal but the long-term neurodevelopmental outcome had this pregnancy continued could not be predicted. We speculate one 14;21 translocation was inherited from her father and one arose de novo being maternal in origin. A previous sibling with psychomotor retardation has an abnormal chromosome complement of 45,XX,dup(7)(q21 leads to pter), t(14;21)(p11;q11). The mother's underlying disease, systemic lupus erythematosis (SLE), and her prior chemotherapy may have contributed to the appearance of these chromosome aberrations. It is interesting that although 14;21 translocations are among the commonest structural chromosome rearrangements in man, there are no previous reports in newborn surveys of a child with 44 chromosomes resulting from the mating of two identical Robertsonian translocation carrier parents.

Homozygosity for constitutional chromosomal rearrangements: a systematic review with reference to origin, ascertainment and phenotype

“…22,27,28 A further case of t(14;22) homozygosity 29 was also considered with some caveats (Table 1; cases 1-10). Those fully documented show various modes of inheritance and methods of ascertainment although some trends emerge.…”

“…19 Exceptions to this included the sole case of unbalanced homozygosity (case 9), that of translocation Down's syndrome, where the parents were unrelated but each heterozygous for t(14;21), 28 and case 7 where only the father was heterozygous, with the second rearrangement arising de novo. 22 For all cases of balanced homozygosity fully reported, ascertainment was following cytogenetic investigation prompted by the presence of an existing RBT within a family member, rather than any specific clinical concern. In all such cases, the proband was phenotypically normal.…”

“…In all such cases, the proband was phenotypically normal. 19,22,24,25,27,29 These include a t(13;14) homozygote identified following an extensive pedigree analysis on a large kindred from an isolated community in Finland (case 4), where data inferred a familial t(13;14) translocation transmitted through nine generations. 24 RBT homozygotes are fertile, as seen in cases 1 and 6, producing one and six children, respectively, with unrelated and karyotypically normal partners.…”

“…Three cases (6)(7)(8) were ascertained during prenatal screening. 22,26,27 Case 7 represents the first published report of RBT homozygosity, with fetal t(14;21) homozygosity ascertained after diagnosis of paternal t(14;21) heterozygosity through family cytogenetic analyses because of an earlier child born with significant motor and mental abnormalities and abnormal karyotype. This marriage was non-consanguinous and the mother was of normal karyotype.…”

“…Of some importance is that homozygosity may be identified during prenatal screening, which may raise clinical and parental concerns regarding the implications of a particular homozygosity. 20,22,23 At present, the data available to counsel parents (and patients) regarding the outcome of any identified homozygosity consists solely of individual case reports or small case series. Although useful, these may have some associated bias because of the presentation of case-specific features.…”