High risk for unbalanced segregation of some reciprocal translocations: A large pedigree containing distal 4q trisomy from t(4;7)(q28;p22)

Abstract

We report on a familial t(4;7)(q28;p22) with 2:2 adjacent-1 unbalanced segregation producing duplication of 4q28-->qter in multiple offspring. Within the large four-generation pedigree, a carrier had a reproductive outcome that was approximately equal for 1) the balanced translocation, 2) normal chromosomes, and 3) viable 4q trisomy or pregnancy loss. The three individuals with chromosomal confirmation of trisomy 4q28-->qter (comprising approximately 1.8% of the haploid autosomal length) had similar mental and developmental retardation, hypotonia, restricted speech, seizures, and facial anomalies but no cardiac, renal, or skeletal anomalies. It is suggested that these latter severe malformations, associated with the classic 4q2 to 3 group of anomalies, were from an imbalance outside 4q28-->qter and were not necessarily related to the relatively large size of the trisomic segment. Multiple different chromosomes are reported to be rearranged with 4q in the production of distal 4q trisomy. The incidence of 4q rearrangement remains unexplained, but once it is present in a family, viability of a large trisomy in 4q seems to explain the number of affected individuals reported.

A multiple translocation event in a patient with hexadactyly, facial dysmorphism, mental retardation and behaviour disorder characterised comprehensively by molecular cytogenetics. Case report and review of the literature

“…Balanced parental translocations may lead to unbalanced rearrangements in the offspring resulting in a clinical phenotype due to additional or deleted chromosomal material with high risk of recurrence [14]. Furthermore, in families with recurrent miscarriages and children with multiple congenital anomalies, cryptic translocations may be the cause [45].…”

Case Report: Phenotype-Gene Correlation in a Case of Novel Tandem 4q Microduplication With Short Stature, Speech Delay and Microcephaly

“…Pure duplications of this kind are important in establishing phenotype-gene correlations (20). Other types of 4q duplications involving translocations with other chromosomes are not reliable cases to establish such correlations as the new location could influence the resulting phenotype (21). Similarly, duplications involving interstitial inversions within 4q could also cause phenotypic changes, and hence unreliable for causal inference studies (22).…”