Supplementary Table S1. Characteristics of 16 patients from 13 families excluded from WES/CNV analysis. ID Cardiac phenotype Age of onset Family history Extra-cardiac features Genetic diagnosis F32P1 DCM 5 weeks Consanguinity Retinitis pigmentosa ALMS1 (NM_015120) c.10483C>T, p.(Q3495*), homozygous dup 4q31.21, five regions > Mb F33P1# DCM with restrictive component and LVH 5 months negative Hypotonia Generalized myopathy MYL2 (NM_000432.3) 403-1G>C, homozygous normal F34P1* DCM neonatal Consanguinity no ALPK3 (NM_020778), c.4736-1G>A, p.Val1579Glyfs*30, homozygous NP F35P1 DCM Third degree AV-block 16 yr Mild developmental delay in brother Ataxia Diabetes mellitus Progressive learning disabilities External opthalmoplegia Epilepsy Kearns Sayre-syndrome, mtDNA del 6 kb in 40% of muscle cells NP F36P1# DCM 6 months Paternal grandfather DCM 3rd degree family member SCD 46 y Brother DCM Hypotonia Areflexia MYL2 (NM_000432.3) 403-1G>C, homozygous normal F36P2# DCM with restrictive component and IVS and RV 4 months Paternal grandfather DCM 3rd degree family member SCD 46 y Sister DCM Hypotonia (mild) Myoclonus MYL2 (NM_000432.3) 403-1G>C, homozygous NP F37P1 DCM 8 months negative Hypotonia Myoclonus Developmental delay Plagiocephaly MYL2 (NM_000432.3) 403-1G>C, homozygous normal
The patient ID is given in bold when a genetic diagnosis could be made. ID Cardiac phenotype Extra cardiac features Prodrome Viral etiology Age of onset SF (%) LV- EF (%) Rhythm disorder CK (U/l) Family history Cardiac screening first degree relatives Endpoint period F1P1 DCM with features of LVNC Dysplastic tricuspid valve no no uk 15 y 12 uk no 46 Father DCM + myopathy Brother DCM with features of LVNC yes, father DCM, brother DCM with features of LVNC - 7 yr F1P2 DCM with features of LVNC Dysplastic tricuspid valve no no uk 14 y 27 43 (last visit) no uk Father DCM + myopathy Sister DCM with features of LVNC yes, father DCM, sister DCM with features of LVNC - 5 yr F2P1 DCM facial dysmorphisms: synophris, strabismus coughing 1 w neg. 10 y 7 uk mild LV conduction defect 199 neg. Not advised LVAD, HtX 1 yr:9 months F3P1 DCM no no IgG EBV pos. in blood antenatal 26 37 no 404 Maternal grandmother DCM 32 yes, normal - 10 yr F3P2 DCM no no NP 8 y 30 uk no NP Mother DCM, Maternal grandmother DCM yes, mother DCM - 10 yr F3P3 DCM NP uk NP neonatal (day 8) <10 uk no NP DCM 3rd degree family member yes, normal partly recovered 23 yr F4P1 DCM no coughing, tiredness 1 w Corona virus pos. in blood 7 y 11 uk atrial tachycardia After ablation atrial bigeminy, neg. yes, mother polymorphic ventricular heart rhythm disorder EP study with ablation, ICD 4 yr
torsades de pointes and long QTc, nsVT F5P1* DCM GSD type 1B, leukopenia, IBD, no neg. 9 y 20 no neg. yes, normal, father not alive died 1 yr:3 months F6P1 DCM high reflexes, high muscular tone of upper extremities, hepatomegaly URTI RSV, B pos. in 3 mo uk no consanguinity not advised died 9 days F7P1 DCM myopathy abdominal pain, pneumonia uk 7 y uk uk no 60 consanguinity yes, neg., father not alive died 10yr:7 months F8P1 DCM with LV hypertrophy hypotonia no neg. antenatal uk uk no uk neg. not advised died 6 weeks F9P1 DCM hypertension no neg. neonatal (day 5) 20 uk no neg. uk recovered 11 days DCM 3-MCCD uk uk 4 mo 8 uk no Father DCM 41, possibly 3-MCCD Brother no DCM yes, father DCM died 9 yr:8 months F11P1 DCM acanthosis nigricans, obesity, strabismus convergens pneumonia, decreased exercise tolerance, abdominal pain, vomiting neg. 17 y uk uk VT SCD SPCm SCD 67 y PPCm yes, normal died 22 days # F10P1
F12P1 DCM no syncope uk 5 y uk uk polymorph VT, ECG Mother mitral valve insufficiency and MVP uk ICD, LVAD, HtX 15 yr F13P1 DCM with restrictive component Diagnosis recently revised as pericarditis constrictiva no sore throat 4 w, abdominal pain/fever 2 w IgG type 1 en 2 pos. in blood 14 24 44 SVTs SCD 57 PPCp uk - 6.5 yr F14P1 DCM, Myxoid MV no coughing, failure to thrive neg. 3 mo 17 uk atrial flutter 77 PMCm heart failure yes, mother mildly dilated LV with hypokinesia + MVP St Jude valve 15 yr F15P1 DCM no abdominal pain 6 w, no fever vomiting, diarrhea 1 w neg. 17 y uk 10 no MPCp enlarged heart PPCp SCD 75 PMCp ischemic CMP, SVTs, ICD yes, father WPW ECMO, LVAD, HtX 7 yr F16P1 DCM no no neg. 7 mo 10 uk nodal tachycardia with AV consanguinity yes, mother NCCM, brother neonatal DCM - 14.5 yr F16P2 DCM ASD type II hydrops foetalis, renal cysts no uk antenatal uk uk bradycardia uk consanguinity yes, mother NCCM, sister DCM died - F17P1 SCD Autopsy: with RVH/LVH epilepsy no uk 10 y uk uk uk uk Mother LVH Father AF yes, normal died - HSV