Hypoplastic left heart syndrome and 21q22.3 deletion

Abstract

Hypoplastic left heart syndrome (HLHS) is a rare congenital heart defect (CHD), associated with extracardiac anomalies in the 15-28% of cases, in the setting of chromosomal anomalies, mendelian disorders, and organ defects. We report on a syndromic female newborn with HLHS and terminal 21q22.3 deletion (del 21q22.3), investigated by Fluorescence In Situ Hybridization (FISH) using a panel of 26 contiguous BAC probes. Although rare, del 21q22.3 has been described in two additional patients with HLHS. In order to investigate the frequency and role of this chromosomal imbalance in the pathogenesis of left-sided obstructive heart defects, we screened for del 21q22.3 a series of syndromic and non-syndromic children with HLHS, aortic coarctation and valvular aortic stenosis, consecutively admitted to our hospital in a three-year period. Although none of the 56 analyzed patients were hemizygous for this region, the present case report and published patients argue that del 21q22 should be added to the list of chromosomal imbalances associated with HLHS. Accordingly, the presence of a cardiac locus mapping in the critical region cannot be excluded.

Outcomes of hypoplastic left heart syndrome and fetal aortic valvuloplasty in a country with suboptimal postnatal management

“…We found that 33% of our initial cases were not isolated, with chromosomal abnormalities found in 9%. LV obstruction is one of the most common congenital heart diseases with a strong genetic basis, and our numbers are in line with those previously reported for a 4% to 9% risk for aneuploidy . Regarding FAV, we had a successful technical procedure in all patients as compared with 80% reported, with two cases (22%) with intraoperative bradycardia, one of which responded to resuscitation.…”

Characterization of two familial cases presenting with a syndromic specific learning disorder and carrying (17q;21q) unbalanced translocations

“…21q22 deletions have been reported in patients showing a wide phenotypic spectrum, including midline defects (frontonasal dysplasia, encephalocele, and corpus callosum agenesis) and learning disability [11]; syndromic hypoplastic left heart [12]; and MCA/ID including microcephaly and ocular coloboma [13]. Thus, it is difficult to evaluate the effect of the 21q partial monosomy on the clinical phenotype observed in the patients here reported.…”

Genotype-Phenotype Analysis of 8q24.3 Duplication and 21q22.3 Deletion in a Chinese Patient and Literature Review

“…Partial deletion of chromosome 21q is a rare chromosomal disorder with heterogeneous phenotype because of unique breakpoint and genetic background [32]. Clinical manifestations of 21q22.3 deletion individuals varied from mild, moderate, severe to lethal depending on the deleted region and concordant chromosomal aberrations [17,19,20]. We present phenotypes of a new case and 7 previously reported cases with 21q22.3 deletion.…”

“…We present phenotypes of a new case and 7 previously reported cases with 21q22.3 deletion. Except for 1 deceased newborn, all of them (7/7) had intellectual disability [20]. Four cases (4/6) had congenital cardiac defects, 2 of which were severe type of hypoplastic left heart [18,20].…”

“…One patient with incomplete clinical data was not included in the table [16]. Seven patients with 21q22.3 deletion and our proband are shown in Table 2 [17][18][19][20][21][22]. We excluded 2 fetuses who were terminated before pregnancy [23,24].…”