Clinical, Cytogenetic, and Biochemical Analyses of a Family with a t(3;13)(q26.2;p11.2): Further Delineation of 3q Duplication Syndrome

Abstract

Chromosomal abnormalities that result in genomic imbalances are a major cause of congenital and developmental anomalies. Partial duplication of chromosome 3q syndrome is a well-described condition, and the phenotypic manifestations include a characteristic facies, microcephaly, hirsutism, synophrys, broad nasal bridge, congenital heart disease, genitourinary disorders, and mental retardation. Approximately 60%–75% of cases are derived from a balanced translocation. We describe a family with a pure typical partial trisomy 3q syndrome derived from a maternal balanced translocation t(3;13)(q26.2;p11.2). As the chromosomal rearrangement involves the short arm of an acrocentric chromosome, the phenotype corresponds to a pure trisomy 3q26.2-qter syndrome. There are 4 affected individuals and several carriers among three generations. The report of this family is relevant because there are few cases of pure duplication 3q syndrome reported, and the cases described here contribute to define the phenotype associated with the syndrome. Furthermore, we confirmed that the survival until adulthood is possible. This report also identified the presence of glycosaminoglycans in urine in this family, not related to the chromosomal abnormality or the phenotype.

Comprehensive review of the duplication 3q syndrome and report of a patient with Currarino syndrome and de novo duplication 3q26.32‐q27.2

“…Although, as outlined by Abreu‐González et al , the clinical manifestation appears to be dominated by the dup(3q) phenotype, these authors reviewed the findings from patients with pure dup(3q) only. Together with the data from our study, there are now at least 31 patients (25 unrelated cases) with a pure dup(3q) reported in the literature ( , , , this study). As correctly countered by Meins et al , a patient reported by Rosenfeld et al showed trisomy 3q21‐q26 but also monosomy for 3q27‐q29 and had to be excluded.…”

“…There is a wide variability of dup(3q) syndrome, even within patients of the same family . According to the extent of the duplication and the clinical variability, the dup(3q) syndrome is suggested a contiguous gene syndrome, caused by more than one gene located in the critical region .…”

“…These reviews, however, did not differentiate between cases arosen from a balanced translocation, also presenting a concomitant deletion on another chromosome and pure partial trisomies. Although, as outlined by Abreu-González et al (6), the clinical manifestation appears to be dominated by the dup(3q) phenotype, these authors reviewed the findings from patients with pure dup(3q) only. Together with the data from our study, there are now at least 31 patients (25 unrelated cases) with a pure dup(3q) reported in the literature (1, 3, 6, 7, 11, 33-47, this study).…”

“…Taken together, around 14% (6/43) of the patients with a pure dup(3q) present with at least one caudal malformation or anomaly. If we adopt the assumption of Abreu-González et al (6), that the clinical manifestation appears to be dominated by the dup(3q), a further nine patients with an additional aberration, or mosaic or tetrasomic for a dup(3q), were shown to display caudal malformations and anomalies ( There is a wide variability of dup(3q) syndrome, even within patients of the same family (6). According to the extent of the duplication and the clinical variability, the dup(3q) syndrome is suggested a contiguous gene syndrome, caused by more than one gene located in the critical region (43,45).…”

“…A dosage-effect of several further candidate genes has also been suggested responsible for the clinical spectrum observed in dup(3q) (6,29,43,45,47). Meins et al (43) reported a dup(3q) with one of the breakpoints located within the NLGN1 gene at 3q26.31.…”