RESUMO
We report a three-generation family with nine patients affected by a combination of cardiac abnormalities and left isomerism which, to our knowledge, has not been described before. The cardiac anomalies include non-compaction of the ventricular myocardium, bradycardia, pulmonary valve stenosis, and secundum atrial septal defect. The laterality sequence anomalies include left bronchial isomerism, azygous continuation of the inferior vena cava, polysplenia and intestinal malrotation, all compatible with left isomerism. This new syndrome is inherited in an autosomal dominant pattern. A genome-wide linkage analysis suggested linkage to chromosome 6p24.3-21.2 with a maximum LOD score of 2.7 at marker D6S276. The linkage interval is located between markers D6S470 (telomeric side) and D6S1610 (centromeric side), and overlaps with the linkage interval in another family with heterotaxy reported previously. Taken together, the genomic region could be reduced to 9.4 cM (12 Mb) containing several functional candidate genes for this complex heterotaxy phenotype.
Assuntos
Bradicardia/complicações , Cardiomiopatias/complicações , Cromossomos Humanos Par 6 , Comunicação Interatrial/complicações , Estenose da Valva Pulmonar/complicações , Adulto , Bradicardia/congênito , Bradicardia/diagnóstico , Bradicardia/genética , Cardiomiopatias/congênito , Cardiomiopatias/diagnóstico , Cardiomiopatias/genética , Pré-Escolar , Mapeamento Cromossômico , Família , Feminino , Ligação Genética , Comunicação Interatrial/diagnóstico , Comunicação Interatrial/genética , Humanos , Recém-Nascido , Volvo Intestinal/congênito , Volvo Intestinal/diagnóstico , Masculino , Pessoa de Meia-Idade , Mutação , Linhagem , Gravidez , Diagnóstico Pré-Natal , Estenose da Valva Pulmonar/congênito , Estenose da Valva Pulmonar/diagnóstico , Estenose da Valva Pulmonar/genética , Síndrome , Trigêmeos/genéticaRESUMO
Most nonsyndromic congenital heart malformations (CHMs) in humans are multifactorial in origin, although an increasing number of monogenic cases have been reported recently. We describe here four new families with presumed autosomal dominant inheritance of left ventricular outflow tract obstruction (LVOTO), consisting of hypoplastic left heart (HLHS) or left ventricle (HLV), aortic valve stenosis (AS) and bicuspid aortic valve (BAV), hypoplastic aortic arch (HAA), and coarctation of the aorta (CoA). LVOTO in these families shows a wide clinical spectrum with some family members having severe anomalies such as hypoplastic left heart, and others only minor anomalies such as mild aortic valve stenosis. This supports the suggestion that all anomalies of the LVOTO spectrum are developmentally related and can be caused by a single gene defect.
