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Table 1 Clinical characteristics of patients with FLNC-associated RCM and congenital myopathy

From: Rare clinical phenotype of filaminopathy presenting as restrictive cardiomyopathy and myopathy in childhood

  Pt1 Pt2 Pt3 Pt4 Pt5 Pt6 Pt7 Pt8 Pt9 Pt10 Pt11 Pt 12
Gender f m f m m f m m m m m m
Genotype chr7: 128485066-7:GC > CT
NM_001458: A1183L
rs1131692185
chr7: 128485076:C > T
NM_001458: A1186V
rs1114167361
chr7: 128485076:C > T
NM_001458: A1186V
rs1114167361
chr7: 128485076:
C > T
NM_001458: A1186V
rs1114167361
chr7: 128485076:C > T
NM_001458: A1186V
rs1114167361
chr7:
128489034:
4926_4927del
NM_001458:
splice cite loss
chr7: 128494628:
G > A
NM_001458:
V2297M
rs1420394583
chr7: 128485076:
C > T
NM_001458: A1186V
rs1114167361
chr7: 128485076:
C > T
NM_001458: A1186V
rs1114167361
chr7:
128497173:
75 bp del
NM_001458: V2522_S2546del
chr7:
128493858: G > A
NM_001458:
G2151S
chr7:
128494598: A > C
NM_001458:
T2287P
ACMG classification P
(PS3, PM1, PM2, PP3, PP4)
P
(PS2, PS3, PM1, PM2, PP3, PP4)
P
(PS3, PM1, PM2, PP3, PP4)
P
(PS2, PS3, PM1, PM2, PP3, PP4)
P
(PS2, PS3, PM1, PM2, PP3, PP4)
P
(PVS1, PS2, PM2, PP3)
LP
(PM1,
PM2, PP2, PP3, PP5)
P
(PS2, PS3, PM1, PM2, PP3, PP4)
P
(PS2, PS3, PM1, PM2, PP3, PP4)
P
(PVS1, PS2, PM2, PP3)
LP
(PM1, PM2, PP3, PP4)
LP
(PM1, PM2, PP3, PP4)
Mutation status De novo De novo Maternal De novo De novo De novo
Initial symptoms initiated clinical contact Slow weight gain, dyspnea Weakness Slow weight gain Slow weight gain, ECG signs of enlarged atria Arthrogryphosis at birth. Inappropriate sinus tachycardia at 6 min walk at age 15 led to first cardiac visit Echo in 6 month—ASD Echo in neonatal period—ASD Stiff neck (Klippel-Feil-like), hypertonus from birth Arthrogryposis (fixed pronation position, unable to supinate) Echo in 6 month—VSD Echo in neonatal period—muscle VSD
Echo in 2 y.o.—atrial dilatation
4 month—Slow Weight Gain, Dyspnea. Echo in 6 month—multiple VSDs, CoA
Age of NM presentation At birth At birth During first year During first year At birth joint contractures During first year During first year At birth At birth During first year During first year 4 month
Family history +
(mother-RCM, AF)

(insignificant ventricular extrasystoles in the mother)
+ (mother, RF ablation for arrhythmia)
Cardiomyopathy phenotype RCM/HCM ASD RCM ASD RCM ASD RCM VSD RCM RCM ASD RCM RCM RCM RCM VSD RCM, muscle VSD RCM, multiple VSDs, Aortic Arch hypoplasia
Age of cardiomyopathy diagnosis 6 months 1.2 y.o 3 years 1 y.o 15 y o 3 y.o 3 y.o 3.5 y.o 2 y.o 6 months at birth 6 months
Conduction disturb RBBB RBBB RBBB AV block I RBBB RBBB AV block I, RBBB RBBB RBBB RBBB, AV block 1
SVT/AF + (1 paroxysm SVT) + (1 paroxysm SVT) + (AF)
VT
SCD
Htx list/performed +/ +/+ +/
Cardiac Enzymes ↑CK-MB × 2
↑Troponin × 1.5
↑CK-MB × 2–4
Normal Troponin
↑CK-MB × 2
Normal Troponin
↑CK-MB × 2.5
Normal Troponin
↑CK-MB × 1.5
Troponin n/a
Normal CK-MB
Normal Troponin
↑CK-MB × 1.5
Normal Troponin
↑ CK-MB × 2.1
Troponin n/a
Normal CK-MB
Troponin n/a
↑CK-MB × 1.16
Normal Troponin
Normal CK-MB
Normal Troponin
Normal CK-MB
Normal Troponin
NT-proBNP ↑ × 83 (10,434 pg/mL) ↑ × 25 (3157 pg/mL) ↑ × 50 (6279 pg/mL) ↑ × 21 (3116 pg/mL) n/a ↑ × 7 (1019 pg/mL) ↑ × 17 (2174 pg/mL) n/a n/a ↑ × 7 (1030 pg/mL) ↑ × 40 (4986 pg/mL) ↑ × 19 (3724 pg/mL)
Cardiac MRI Not performed Not performed The pericardium is not changed. Severe dilatation of both atria; ventricles are not dilated. LV ejection fraction at the lower limit of the norm. No clear pathological contrast delay The pericardium is not changed. Severe dilatation of both atria; ventricles are not dilated. LV ejection fraction is normal. On delayed post-contrast images in the mid-apical part of the antero-septal region, minimally pronounced intramural fibrous changes are determined Not performed Not performed The pericardium is not changed. The right atrium is dilated, the left atrium is moderately dilated, the ventricles are not dilated. No clear pathological contrast delay agent in the LV myocardium Not performed Not performed The MRI picture may correspond to a non-compact LV myocardium. Dilation of the LA. On delayed post-contrast images in the basal parts of the antero-septal region, minimally pronounced intramural fibrous changes are determined Not performed Not performed
Limb-girdle weakness + + + + + + +
Distal muscle weakness + + +
Difficulty toe walking + + + (with difficulties)
Winged scapulas + + + + + + + +
Facial weakness + + + + +
Ptosis + +
Camptodactyly + (5th fingers) +
Inability to Rise from squatting
Position
+ + +   − (balance problems)
Arthrogryposis + (at birth) + (at birth) + (at birth) + + +
Scoliosis + + (severe progressive) + (severe, progressive—> scoliosis surgery) + + +
Pectus deformation Pectus excavatum Pectus carinatum
Hip dysplasia + + + + +
Torticollis + + +
Joint contracture + + +
Marked contractures shoulders. Mild contractures hips, ankles, index toes, elbows, wrists, right thumb
+ (Ankle stifness) + + (forearm) + (Ankle stifness)
Hernia White line hernia Umbilical hernia White line hernia + Umbilical hernia
Other Microsomia Microsomia Growth retardation. Pes equinus
Long QT
Muscle biopsy: centrally located nuclei. Cytoplasmic body myopathy Short stature of mixednesis; Hypoglycemia, long QT Periorbital cyanosis Sprengler deformity, Noonan-like phenotype Micromandibula, short neck, hyperkyphosis, pedes plani, undescended testes Presyncope, Long QT Microsomia, Pulmonary hypertension, coagulopathy, Diffuse non-toxic goiter, subclinical hypothyroidism
CNS Pyramid insufficiency
Clonical seizures
Pyramid insufficiency  
ENMG Diffuse myopathic pattern Diffuse myopathic pattern
Neuropathy
Diffuse myopathic pattern Sensory polyneuropathy in the legs and arms Not performed Diffuse sensory neuropathy Normal Normal Diffuse myopathic pattern
Muscle Enzymes Normal CK
↑LDH × 1.5
↑CK × 1.5–4
↑LDH × 1.5
↑CK × 1.2
↑LDH × 1.5
↑CK × 1.32
↑LDH × 1.84
Transaminases normal Normal CK
↑LDH × 1.45
Normal CK
Normal LDH
↑CK × 2.8, ↑LDH × 1.4, ↑myoglobin × 1.8 ↑CK × 3.8
normal myoglobin & LDH
Normal CK
Normal LDH
Normal CK
Normal LDH
Normal CK
↑LDH × 1.15
Outcome Listed for HTx at 3 y.o Death at 2 years of age Death at 9 years of age   HTx at 18 y.o   Listed for HTx at 12 y.o ICD     
  1. AF atrial fibrillation, ASD atrial septal defect, AVBI atrio-ventricular block I, CoA coarctation of the aorta, CK creatine kinase, CK-MB creatine kinase myocardial band, CNS central nervous system, ECG electrocardiography, ENMG electroneuromyography, F female, HCM hypertrophic cardiomyopathy, HTx heart transplantation, LDH Lactate dehydrogenase, LV left ventricle, M male, MRI magnetic resonance imaging, RBBB right bundle branch block, RCM restrictive cardiomyopathy, ICD Implantable Cardioverter Defibrillator, SCD sudden cardiac death, SVT supraventricular tachycardia, VSD ventricle septal defect, VT ventricular tachycardia