Prenatal detection and outcome of congenital diaphragmatic hernia (CDH) associated with deletion of chromosome 15q26: Two patients and review of the literature

Abstract

Congenital diaphragmatic hernia (CDH) is a severe birth defect characterized by a defect in the diaphragm with pulmonary hypoplasia and postnatal pulmonary hypertension. Approximately 50% of CDH cases are associated with other non-pulmonary congenital anomalies (so called non-isolated CDH) and in 5-10% of cases there is a chromosomal etiology. The majority of CDH cases are detected prenatally. In some cases prenatal chromosome analysis reveals a causative chromosomal anomaly, most often aneuploidy. Deletion of 15q26 is the most frequently described structural chromosomal aberration in patients with non-isolated CDH. In this paper we report on two patients with a deletion of 15q26 and phenotypes similar to other patients with CDH caused by 15q26 deletions. This phenotype consists of intra-uterine growth retardation, left-sided CDH, cardiac anomalies and characteristic facial features, similar to those seen in Fryns syndrome. We propose that when this combination of birth defects is identified, either pre- or postnatally, further investigations to confirm or exclude a deletion of 15q26 are indicated, since the diagnosis of this deletion will have major consequences for the prognosis and, therefore, can affect decision making.

Rare DNA copy number variants in cardiovascular malformations with extracardiac abnormalities

“…Several published reports have examined smaller cohorts of patients with complex clinical presentations and described non-recurrent contiguous gene deletion syndromes contributing to CVMs, including 1p36 monosomy, 30 15q26 deletion, [31][32][33][34][35] Wolf-Hirschhorn syndrome (4p16.3 deletion), 36 Cri-du-chat syndrome (5p15.2 monosomy), 37 Miller-Dieker lissencephaly syndrome (17p13.3 deletion) 38 and 17q23.1q23.2 microdeletion syndrome. 18 Examples where such an approach was successful in identifying specific dosage-sensitive genes include JAG1 in Allagile Figure 1 Variable de novo (DN) deletions of 16q24.3 observed in multiple subjects with CVMs and ECAs.…”

Identification of chromosome 15q26 terminal deletion with telomere sequences and its bearing on genotype-phenotype analysis

“…Thus, although underlying factor(s) for the extremely high IGF1 level remains to be clarified, the present data indicate that serum IGF1 level can be markedly elevated in patients with IGF1R haploinsufficiency. mosome 15 and unbalanced translocation involving 15q26 [12], genotype-phenotype analysis of 15q26 deletion is difficult in complex chromosomal rearrangements because of accompanying chromosomal aberrations.…”

“…rangements involving 15q26 than in simple terminal 15q deletions [1,12], because chromosomal imbalance is more severe in complex chromosomal rearrangements. In addition, if a gene(s) for such features is present on distal 15q, it is likely that such a gene(s) was preserved in this patient with a relatively small deletion, or that loss of the gene(s) did not cause clinically discernible phenotypes in this patient because of low penetrance.…”

Gene expression in the developing diaphragm: significance for congenital diaphragmatic hernia

“…The first and best-characterized critical region to be identified is located at 15q26; a deletion of this part of chromosome 15 has been shown to account for ϳ1.5% of CDH cases and is associated with very high mortality (15,39,53). The spectrum of anomalies produced by 15q26 deletion is phenotypically most similar to Fryns syndrome (38,58). Several other regions of the human genome have also been identified as putative CDHcritical regions, including 1q41-1q42, 4p16.3, 8p23.1, and 8q22-8q23 (33,60).…”