Hypoplastic-Left-Heart Syndrome in Siblings

Kojima, Hisaya; Ohgimi, Yoshio; Mizutani, Kazuhiro; Nishimura, Yoshio

doi:10.1016/s0140-6736(69)90418-8

Cited by 11 publications

(5 citation statements)

References 4 publications

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“…Accumulating evidence from multiple sources supports a strong genetic involvement in the causation of these defects. This includes multiple case reports detailing recurrences of AVS, COA, and HLH within families [Kojima et al, 1969; Beekman and Robinow, 1985; Menahem, 1990; Grobman and Pergament, 1996; Stoll et al, 1999], high incidence among the chromosomal defects, Turner syndrome (45,X) and Jacobsen syndrome (11q23del) [van Egmond et al, 1988; Mazzanti and Cacciari, 1998; Grossfeld et al, 2004], and occurrence in single gene disorders, such as Holt‐Oram syndrome ( TBX5 ) [Basson et al, 1997] and ZIC3 [Ware et al, 2004].…”

Section: Introductionmentioning

confidence: 99%

Inheritance analysis of congenital left ventricular outflow tract obstruction malformations: Segregation, multiplex relative risk, and heritability

et al. 2005

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The left ventricular outflow tract (LVOTO) malformations, aortic valve stenosis (AVS), coarctation of the aorta (COA), and hypoplastic left heart (HLH) constitute a mechanistically defined subgroup of congenital heart defects that have substantial evidence for a genetic component. Evidence from echocardiography studies has shown that bicuspid aortic valve (BAV) is found frequently in relatives of children with LVOTO defects. However, formal inheritance analysis has not been performed. We ascertained 124 families by an index case with AVS, COA, or HLH. A total of 413 relatives were enrolled in the study, of which 351 had detailed echocardiography exams for structural heart defects and measurements of a variety of aortic arch, left ventricle, and valve structures. LVOTO malformations were noted in 30 relatives (18 BAV, 5 HLH, 3 COA, and 3 AVS), along with significant congenital heart defects (CHD) in 2 others (32/413; 7.7%). Relative risk for first-degree relatives in this group was 36.9, with a heritability of 0.71-0.90. Formal segregation analysis suggests that one or more minor loci with rare dominant alleles may be operative in a subset of families. Multiplex relative risk analysis, which estimates number of loci, had the highest maximum likelihood score in a model with 2 loci (range of 1-6 in the lod-1 support interval). Heritability of several aortic arch measurements and aortic valve was significant. These data support a complex but most likely oligogenic pattern of inheritance. A combination of linkage and association study designs is likely to enable LVOTO risk gene identification. This data can also provide families with important information for screening asymptomatic relatives for potentially harmful cardiac defects.

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Section: Introductionmentioning

confidence: 99%

Inheritance analysis of congenital left ventricular outflow tract obstruction malformations: Segregation, multiplex relative risk, and heritability

et al. 2005

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“…2 Reports of familial malformation syndromes, such as those involving an atrial septal defect, 3 a hypoplastic left ventricle, 4 and the tetralogy of Fallot, 5 strongly suggest that genetic factors play a part in a number of heart defects. Recently, the DiGeorge syndrome (characterized by aortic-arch anomalies and hypocalcemia) has been mapped to a locus at 22q11, 6 and the Holt-Oram syndrome (heart-hand syndrome) to 12q2.…”

mentioning

confidence: 99%

Mutations of theConnexin43Gap-Junction Gene in Patients with Heart Malformations and Defects of Laterality

et al. 1995

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“…Multiple investigations, nonetheless, support a multi-factorial mode of inheritance. 6,7,10 Although it is well recognized that hypoplastic left heart syndrome is frequently associated with significant extracardiac abnormalities, in our review of the literature we were unable to find other reported patients with both hypoplastic left heart syndrome and spinal muscular atrophy. Clinicians must remain aware of such genetic disorders, which may considerably alter the clinical management of patients with congenital heart disease.…”

Section: Discussionmentioning

confidence: 65%

“…[3][4][5] In over nine-tenths of afflicted individuals, all types of the disease are linked to the same region of chromosome 5q. 6,7 This region contains the survival motor neuron gene, which may have areas of inversion, duplication, or deletion. 8 Hypoplastic left heart syndrome is known to be associated with certain genetic conditions, including Turner's syndrome, or 45 XO, Jacobsen syndrome characterized by terminal deletion of chromosome 11q, Trisomy 13 and 18, Holt-Oram syndrome, and duplication of chromosome 12.…”

Section: Discussionmentioning

confidence: 99%