Table 1.

Clinical features

	Family 1 (Patients 1 and 2)	Family 2 (Patient 3)	Family 3 (Patient 4)	Family 4 (Patient 5)
Mutation	c.106632–106633delTG p.Ser35469Serfs*11 homozygous	c.C102748T p.Arg34175*; c.C106057T p.Gln35278*	c.T66920A p.Val22232Glu; c.102282delT p.Asn34020Thrfs*9	c.G9388+1C p.Glu2989Glufs*4 c.T102439C p.Trp34072Arg
Cardiac septal defects	No	Neonatal ASD	ASD, VSD; surgical repair in the 1st year LV to RA shunt repaired at 4 years	Small muscular VSD
Cardiomyopathy	Asymptomatic DCM detected at 19 years in the elder brother. Normal echocardiography in the younger brother at 16 years	DCM from 16 years. Cardiac MRI at 23 years: diffuse biventricular and septal gadolinium enhancement (fibrosis), no PAH. RV: dilatation, systolic dysfunction (SF 21%), hypokinesia > apical LV: EF 40%, Septum: hypokynesia, paradoxical movement, MRI hyposignal	Arrhythmia and SVT at the age of 8 years DCM from the age of 13 years (SF 11%) Cardiac transplant at 14 years	LVNC Slightly depressed LV function at birth At the age of 1 month, DCM with EF 10–15% Terminal heart failure and cardiac transplant at 4 years
Rhythm disturbances	No	Holter: ventricular extrasystoles++	Arrhythmia and SVT at the age of 8 years	NA
Early motor development	Normal	Neonatal hypotonia, delayed head control, walked at the age of 2 years	Normal	Neonatal hypotonia, severe motor skill delay, head drop, sitting and standing with support at the age of 19 months
First musculoskeletal signs	From the age of 2 years: weakness, elbow and ankle contractures	Neonatal hypotonia, poor suckling (NG tube), never run or jumped, difficulties climbing stairs, steppage (7 years)	Never able to run From the age of 5 years: difficulties climbing stairs	Decreased fetal movements, dislocated hips, bilateral hip dysplasia, thoracic kyphosis
Joint contractures	Moderate/severe, elbows and ankles	Severe, elbows and ankles, from the age of 6 years	Mild, ankles	Elbow, hip, knee, digit (distal AMC)
Rigid spine	NA	Yes, severe	Yes, moderate	Yes
Scoliosis	NA	Yes, from the age of 12 years Arthrodesis at the age of 13 years	Yes, mild, thoracic	Yes, kyphosis from birth, progressive kyphoscoliosis in childhood
Respiratory failure	No	FVC 800 ml, FEV1 700 ml	No	NA
Ptosis	NA	No	Mild	No
CK	4 × N	2–5 × N	195 U/l	NA
Muscle weakness evolution	Slowly progressive	Slowly progressive	Stable	Stable AMC: improving Intrasurgical spinal cord infarction resulting in paraplegia at the age of 4 years
Muscle biopsy	Minicores, central nuclei, dark oxidative areas, type 1 predominance (16 years)	Minicores, central nuclei +++, target-like fibers, central basophilic areas, type 1 predominance (2 years, 14 years and 25 years)	Minicores, central nuclei, central basophilic areas, dark oxidative areas, type 1 uniformity (12 years)	Minicores, central nuclei, type 1 predominance, mild endomysial fibrosis (15 months)
Walking ability	Good	200 m	Good	Never walked
Others		Mild dysphagia Large neck Flat, retractile thorax	Cleft soft palate Webbed short neck, hypertelorism Radioulnar synostosis	Short neck Finger ulnar deviation, bilateral camptodactyly Low-set ears
Parents age at last echocardiogram and ECG (years)	51 and 52	53 and 55	49 and 50	38 and 42

NCBI accession numbers: NM_001267550.1 and NP_001254479.

AMC, arthrogryposis multiplex congenita; ASD/VSD, atrial/ventricular septum defect; CK, creatine kinase; DCM, dilated cardiomyopathy; ECG, electrocardiogram; EF, ejection fraction; FEV1, forced expiratory volume 1; FVC, forced vital capacity; LV, left ventricle; LVNC, left ventricular non–compaction; MRI, magnetic resonance imaging; NA, non-available data; NG, nasogastric; PAH, pulmonary artery hypertension; RA, right atrium; SF, shortening fraction; SVT, Supraventricular tachycardia.