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

Abstract

Partial duplications of the long arm of chromosome 3, dup(3q), are a rare but well-described condition, sharing features of Cornelia de Lange syndrome. Around two thirds of cases are derived from unbalanced translocations, whereas pure dup(3q) have rarely been reported. Here, we provide an extensive review of the literature on dup(3q). This search revealed several patients with caudal malformations and anomalies, suggesting that caudal malformations or anomalies represent an inherent phenotypic feature of dup(3q). In this context, we report a patient with a pure de novo duplication 3q26.32-q27.2. The patient had the clinical diagnosis of Currarino syndrome (CS) (characterized by the triad of sacral anomalies, anorectal malformations and a presacral mass) and additional features, frequently detected in patients with a dup(3q). Mutations within the MNX1 gene were found to be causative in CS but no MNX1 mutation could be detected in our patient. Our comprehensive search for candidate genes located in the critical region of the duplication 3q syndrome, 3q26.3-q27, revealed a so far neglected phenotypic overlap of dup(3q) and the Pierpont syndrome, associated with a mutation of the TBL1XR1 gene on 3q26.32.

A Pure 2-Mb 3q26.2 Duplication Proximal to the Critical Region of 3q Duplication Syndrome

“…Therefore, pure dup(3q) is rare, and only 31 cases (25 unrelated cases) have been described until now [reviewed by Dworschak et al, 2017]. In this study, we report a pure duplication of 2 Mb at 3q26.2 not encompassing the previously proposed critical region of dup(3q) syndrome.…”

“…The duplicated segment in the patient described here does not encompass the previously proposed critical region of 3q26.3q27 for dup(3q) syndrome [reviewed by Dworschak et al, 2017]; nevertheless, when comparing the phenotype of our patient with the clinical manifestations of the few cases of pure dup(3q) syndrome previously reported encompassing the q26.2 region ( Table 1 ), they share the main characteristics of the syndrome, including intellectual disabilitity, synophrys, wide nasal bridge, dysmorphic ears, clinodactyly, and cardiac defects.…”

How to Explore Fetal Sacral Agenesis Without Open Dysraphism: Key Prenatal Imaging and Clinical Implications

“…After sonographic detection of sacral agenesis, a comparative genomic hybridization (CGH) array should be offered, especially in cases of associated malformations. The presence of an anorectal malformation is a warning sign and should prompt consideration of amniocentesis because there is an increased incidence of anorectal malformations in patients with trisomy 21 . Some chromosomal deletions or duplications have been reported in the literature: 18p11.2 deletion and 3q26.32‐q27.2 duplication .…”

Less common underlying genetic diagnoses found in a cohort of 139 individuals surgically corrected for craniosynostosis

“…While the remaining individuals with cytogenetic abnormalities identified in this population (Xp11 deletion, 2q37 deletion, 1q21 duplication, 6q21q22 deletion, 3p26 deletion, 3q26 duplication, and trisomy 21) had expected phenotypic features for the described corresponding alteration, the origin of their craniosynostosis could not be explained easily. Extensive review of the medial literature and public databases revealed occasional reports of craniosynostosis for overlapping alterations in some instances but this was insufficient to establish a direct causative link (Dworschak et al, ; Milani et al, ; Rosenfeld et al, ; Shukla et al, ; Siu et al, ; Wilson et al, ). The only instance of a recurrent alteration in this study was a 2q37 deletion (region of overlap: hg19: 239, 315, 476–242, 783, 384) seen in two individuals, one with metopic and the other with sagittal craniosynostosis.…”