Genetic causes for autosomal recessive forms of dilated cardiomyopathy (DCM) are only rarely identified, although they are thought to contribute considerably to sudden cardiac death and heart failure, especially in young children. Here, we describe 11 young patients (5–13 years) with a predominant presentation of dilated cardiomyopathy (DCM). Metabolic investigations showed deficient protein N-glycosylation, leading to a diagnosis of Congenital Disorders of Glycosylation (CDG). Homozygosity mapping in the consanguineous families showed a locus with two known genes in the N-glycosylation pathway. In all individuals, pathogenic mutations were identified in DOLK, encoding the dolichol kinase responsible for formation of dolichol-phosphate. Enzyme analysis in patients' fibroblasts confirmed a dolichol kinase deficiency in all families. In comparison with the generally multisystem presentation in CDG, the nonsyndromic DCM in several individuals was remarkable. Investigation of other dolichol-phosphate dependent glycosylation pathways in biopsied heart tissue indicated reduced O-mannosylation of alpha-dystroglycan with concomitant functional loss of its laminin-binding capacity, which has been linked to DCM. We thus identified a combined deficiency of protein N-glycosylation and alpha-dystroglycan O-mannosylation in patients with nonsyndromic DCM due to autosomal recessive DOLK mutations.

The Bardet-Biedl syndrome is an autosomal recessive disorder of polydactyly, obesity, tapetoretinal degeneration, mental retardation, hypogenitalism, and renal involvement. A high incidence of congenital and acquired heart disease was reported in the former "Laurence-Moon-Biedl-Bardet" syndrome. However, since the establishment of the Bardet-Biedl syndrome as a separate clinical entity, cardiac involvement has not been evaluated in this disorder. We have performed echocardiographic studies on 22 patients with the Bardet-Biedl syndrome from three extended, highly inbred Bedouin families. In addition to previously reported congenital heart defects we have observed hypertrophy of the interventricular septum and dilated cardiomyopathy. Our findings of cardiac involvement in 50% of the cases suggest that echocardiographic examination should be included in the clinical evaluation and follow-up of patients with Bardet-Biedl syndrome.

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So-called 'absent pulmonary valve syndrome' is a rare cardiac malformation, usually associated with tetralogy of Fallot. Congenital absence of the leaflets of the pulmonary valve is less common when the ventricular septum is intact. Characteristic features of the syndrome include dysplasia or absence of the pulmonary valvar leaflets, permitting severe pulmonary regurgitation, and aneurysmal dilation of the pulmonary arteries. The purpose of our study was to review our experience with patients diagnosed as having the absent pulmonary valve syndrome, and to describe their clinical presentation, natural history, and outcome. We reviewed retrospectively data from 18 patients with absent pulmonary valve syndrome, 10 boys and eight girls, treated between March 1983 and May 2003. We identified two groups of patients, one made up of 11 patients with a ventricular septal defect, in whom the morphology of the subpulmonary outflow tract was phenotypic for tetralogy of Fallot, and another group, with seven patients, having an intact ventricular septum. Family history of congenital heart disease was common only in patients with ventricular septal defect, being found in 73%, all of whom were diagnosed during infancy with variable respiratory distress. Diagnosis was delayed in 43% of the patients with an intact ventricular septum. Cardiac surgery was performed in eight patients with ventricular septal defect (73%), compared to only two patients (28%) with an intact ventricular septum. Overall mortality was 28%, with five patients dying. Although our sample was small, two clinical patterns emerged depending on the presence or absence of a ventricular septal defect. Patients with a ventricular septal defect and phenotypic features of tetralogy of Fallot have a strong family history of congenital cardiac disease, develop respiratory symptoms during infancy and exhibit a variable prognosis, despite cardiac surgery. Patients with an intact ventricular septum are usually asymptomatic, present later in life, and show a relatively benign prognosis.