Table 1

Clinical Phenotype Features of FLNC Truncation Carriers and DCM-Affected Individuals

FamilyDNFDC057DNFDC079DNFDC195TSFDC029TSFDC031TSFDC043TSSDC130
IndividualII:1II:2III:1II:2II:2III:4III:6III:7IV:1II:2III:1I:2II:3
SexMFFMFFMFMMMFM
Age at diagnosis, yrs59543339624635342744207620
VariationFrameshiftStopgainSplicingSplicingSplicingSplicingStopgain
Nucleotide changec.5669-1delGc.2119C>Tc.2930-1G>Tc.7251+1A>Gc.7251+1A>Gc.3791-1G>Ac.805C>T
AA changep.G1891Vfs61Xp.Q707Xp.K977fsp.Y2381Gfsp.Y2381Gfsp.G1264fsp.R269X
Secondary mutationSCN5A
c.5270delT; p.F1757fs
NYHA functional classIIIIIIIIIIIIIIIIIIIIIIIII
SymptomsDOE, fatiguePalpitations, SOBPre-syncope, SOBSyncopePalpitationsPalpitations, SOB, chest painAsymptomatic, SCDPalpitationsFatigue, palpitationsSOBPre-syncopeFatigue, SOBSyncope
ArrhythmiasPACs, PVCs, NSVTPVCs, AF, sustained VT (1997)No arrhythmiasMultiform PVCsSustained VT, PVCs (800/24 h), NSVTPVCs (900/24h), NSVTNANo arrhythmiasPACs, PVCs (93/24h)NSVT, couplet (154/24h)PAF, SVT, SAECGAF, frequent PVCsSustained VT
ECGAVB1, incomplete LBBBAVB1, LVHNonspecific ST changesPM, AICD, nonspecific ST changesPVCsLow voltagesNANormalRBBBNormalNormalAVB, RBBB, LAFBSB, IV conduction delay, nonspecific ST changes
LVEDD, cm6.45.65.47.25.4, inferobasal hypokinesis5.5NA4.95.35.75.5, inferobasal hypokinesis6.46.9
LVEF, %451020155232NA634547451438
CK, U/l11810656NA5632NA508010370NA130
RVNormalMild dilatationDilatationMild dilatation and dysfunctionNormal (FS 53%)Normal (FS 60%)NANormalNormalNAMild dilatation and dysfunction (FS 33%)Dilatation and dysfunctionNormal
OutcomeNYHA functional class II, LVEF 21%, CRT, AICD, LVAD (2016)Severe LV and RV dysfunction, heart transplant (2009)Normalized LVEF 60%Appropriate AICD discharge (2016)NYHA functional class I, LVEF 51%NYHA functional class II, NCDCardiomegaly at autopsyNYHA functional class INYHA functional class I, palpitations, LVEF 52%NYHA functional class II, SCDNYHA functional class 1, palpitations, LVEF 40%PM, heart failure death (2008)Recurrent sustained VT, AICD (1999), NYHA functional class II
Follow-up, yrs11111615141515417914

Families DNFD057, TSFDC029, and TFDC031 are previously reported variants (9).

AA = amino acid; AF = atrial fibrillation; AICD = automatic implantable cardioverter-defibrillator; AVB = atrioventricular block; CK = creatine kinase; CRT = cardiac resynchronization therapy, DOE = dyspnea on exertion; ECG = electrocardiogram; FS = fractional shortening, IV = intraventricular; LAFB = left anterior fascicular block; LBBB = left bundle branch block; LVAD = left ventricular assist device; LVEDD; left ventricular end-diastolic dimension; LVEF = left ventricular ejection fraction; LVH = left ventricular hypertrophy; NA = not available; NCD = noncardiac death; NYHA = New York Association functional class; PAF = paroxysmal atrial fibrillation; PM = pacemaker; PAC = premature atrial contraction, PVC = premature ventricular contraction; RBBB = right bundle branch block; RV = right ventricle; SAECG = signal-averaged electrocardiography; SB = sinus bradycardia; SCD = sudden cardiac death; SOB = shortness of breath; ST = sinus tachycardia; VT = ventricular tachycardia.

  • Individual III:6 died before enrollment; DNA was not available for genetic testing.

  • Normal CK level is <223 U/l.