Table 2.

Clinical characteristics of humans with SPEG mutations

Patient	Gender/age	Genotype	Skeletal muscle findings	Cardiac findings	Ref
1	Female/died at 3 weeks	Homozygous c.6697C>T p.G2233* Pathogenic Nonsense	Severe hypotonia, respiratory insufficiency	No cardiac evaluation	10
2	Female/6 years	Heterozygous c.3709_3715 + 29del36 p.T1237Sfs*46 Pathogenic Frameshift and c.4276C>T p.R1426* Pathogenic Nonsense	Severe hypotonia, ophthalmoplegia, facial weakness, tracheostomy for respiratory insufficiency, sat unsupported at 2, unable to walk	Normal cardiac function at birth, at 2 months of age: dilated cardiomyopathy, severe depression of systolic function, left and right ventricular diastolic dysfunction. Drug treatments resulted in normal ventricular function by 1 year of age	10
3	Male/19 months	Heterozygous c.2915_2916delCCinsA p.A972Dfs*79 Pathogenic Frameshift and c.8270G>T p.G2757V Likely pathogenic Missense	Severe hypotonia, facial weakness, unsupported sitting at 18 months	Foetal bradycardia, dilated cardiomyopathy at 1 month of age, decreased left ventricular function, mitral insufficiency	10
4	Male/3 years	Homozygous c.1626_1627insA p.T544Dfs*48 Pathogenic Frameshift	Severe hypotonia, ophthalmoplegia with mild ptosis, polyphasic motor unit potentials on EMG, unsupported sitting at 12 months, unable to walk	Foetal bradycardia, no cardiomyopathy	28
5	Male/8 years	Homozygous c.9586C>T p.R3196* Pathogenic Nonsense	Severe hypotonia, facial weakness, walking with assistance at 3 years, walking independently at 4 years, normal eye movement	Foetal bradycardia, dilated cardiomyopathy, left ventricular ejection fraction 31% and worsening, mild mitral insufficiency	28
6	Female/10 years	Heterozygous c.1071_1074dup p.K359Vfs*35 Pathogenic Frameshift and c.4399C>T p.R1467* Pathogenic Nonsense	Hypotonia, positive Gower’s sign, walking independently at 30 months	Reduced myocardial contraction at 5 years that normalized with 1 year of drug treatment, no dilated cardiomyopathy	29
7	Male/died 19 weeks	Homozygous c.7119C>A p.Y2373* Pathogenic Nonsense	Floppy infant, no deep tendon reflexes, motor nerve conduction velocity amplitudes of median and peroneal nerve were below normal range (axonal neuropathy), polyphasic motor unit potentials	At 10 weeks fractional shortening of 30% and normal inner diameter of left ventricle, enlarged atria, abnormal trabeculation, intratrabecular recesses as pathognomonic of left ventricular non-compaction (LVNC)	30
8	Male/died 17 years	Homozygous c.9185_9187delTGG p.V3062del Likely pathogenic In-frame deletion	Proximal muscle weakness diagnosed at age 4, ophthalmoplegia at 12	At age 6 biventricular hypertrophy, severe left ventricular dilation, poor muscle contractility, progressive dilated cardiomyopathy: fractional shortening went from 20% at age 10 to 9% at age 16, severe mitral valve insufficiency, died of cardiopulmonary insufficiency	31
9	Female/6.5 years	Heterozygous c.2183delT p.L728Rfs*82 Pathogenic Frameshift and c.8962_8963insCGGG GCGAACGTTCGTG GCCAAGAT p.V2997Gfs*52 Likely pathogenic Frameshift	Hypotonia, facial weakness, axial hypotonia, proximal muscle weakness, ophthalmoplegia, bilateral ptosis, intermittent strabismus, walking at 2 years	Sinus tachycardia, no signs of contractile dysfunction	31
10	Female/died 3 days (Twin of P11)	Homozygous c.8710A>G p.T2904A Uncertain significance Missense	Facial weakness, ptosis, respiratory insufficiency, hypotonia, axial muscle weakness	Sinus tachycardia, right atrium abnormality, dilated cardiomyopathy	32
11	Female/died 5 days (Twin of P10)	Homozygous c.8710A>G p.T2904A Uncertain significance Missense	Facial weakness, ptosis, respiratory insufficiency, hypotonia, axial muscle weakness	Sinus tachycardia, right atrium abnormality, dilated cardiomyopathy	32