TABLE 1.
MUTATION AND CLINICAL PHENOTYPE
| Family; country of origin |
Mutation (protein) |
Mutation (cDNA)* | Number of affected family members |
First symptom and age at presentation |
Ankle dorsiflexion weakness |
Long finger extensor weakness |
Site of other weakness | Other | ClinVar accession number |
|---|---|---|---|---|---|---|---|---|---|
| 1 UK |
p.Leu1481Pro^ | c.4442T>C | Six over 3 generations | “Toe walker” when commenced walking at 1 year | Y | Y, by 8 years | Cervical spine, trunk, scapular, ankle inversion by 15 years | TA contractures and hamstrings | SCV000120158 |
| 2 USA |
p.Glu1508del | c.4522_4524delGAG | One | Scoliosis aged 10 years | Y | Y, by 21 years | Neck flexors, hip extensors | TA contractures, cervical paraspinal, hips | SCV000120159 |
| 3 Belgium |
p.Glu1508del | c.4522_4524delGAG | Two over 2 generations | high stepping gait in both, at 4 yrs and 7 yrs respectively | Y | Y, by 15yrs | Weakness of deltoid, neck flexor, sternocleidomastoid, triceps, wrist extension, hip adductor, quads, glutei, posterior tibial, toe flexors | TA contractures | SCV000120159 |
| 4 Canada |
p.Gln1541Pro^ | c.4622A>C | Eight over 4 generations | Foot drop and awkward gait in early childhood | Y | In 30’s to 40’s | Proximal leg | 3 had calf hypertrophy | SCV000119900 |
| 5 Australia |
p.Thr1599Pro^ | c.4795A>C | Six over 3 generations | Foot drop when started walking at one year | Y | Y as adult | Nil | Nil | SCV000119901 |
| 6 UK |
p.Arg1608Pro^ | c.4823G>C | Two over 2 generations | Floppy baby during first months of life | Y | Y | Generalised. Loss of neck control, wheelchair dependant by 15 yrs | Widespread joint contractures | SCV000119902 |
| 7 UK |
p.Leu1612Pro^ | c.4835T>C | One | Footdrop aged 4 years | Y | N | Neck extensor contractures, mild hamstring contractures | SCV000119903 | |
| 8 USA |
p.Lys1617del | c.4849_4851delAAG | Nine over 5 generations | Proband presented in infancy with bilateral footdrop | Y | Y by 6th decade | Neck flexors/extensors, finger flexors, generalised | SCV000119904 | |
| 9 UK |
p.Lys1617del | c.4849_4851delAAG | Six over 3 generations | Footdrop when started walking at one year | Y | Y | Hip and knee flexion, shoulder and elbow, neck flexion | TA contractures | SCV000119904 |
| 10 UK |
p.Lys1617del | c.4849_4851delAAG | One | Ankle weakness at 5 years | Y | Y by 31 years | Shoulder girdle, wrist flexion/extension, proximal leg | TA contractures | SCV000119904 |
| 11 USA |
p.Lys1617del | c.4849_4851delAAG | One | Always ran on her toes, presented aged 2 years; tripping a lot by 7 years | Y | Not by 10 years | Neck flexion, mild diffuse weakness | - | SCV000119904 |
| 12 UK |
p.Lys1617del | c.4849_4851delAAG | One | Unusual gait, toe-walking at 2.5 years | Y | Not by 10 years | Hip girdle, finger extensor weakness | TA contractures | SCV000119904 |
| 13 Spain |
p.Ala1636Pro^ | c.4906G>C | 20 over 4 generations | Abnormal gait, tripping easily, onset from early childhood to 4th decade | Y | Y in some patients | Neck flexors. Limb girdle (predominantly affecting pelvic muscles) and proximal leg | TA contractures, calf hypertrophy in some, myalgia | SCV000120167 |
| 14 USA |
p.Leu1646Pro ^ | c.4937T>C | Six over 3 generations | Tripping easily, 5 years in one, 7 years in another | Y | Y by 33 years | Scapular winging, hip flexion, | TA contractures | SCV000119905 |
| 15 Italy |
p.Arg1662Pro ^ | c.4985G>C | Three | Footdrop at 3 years | Y | Not by 7 years | nil | nil | SCV000119906 |
| 16 UK |
p.Glu1669del^ | c.5005_5007delGAG | Seven over 3 generations | Footdrop at 3 years | Y | Y by 72 years | Extensor digitorum brevis | Neck extensor contractures | SCV000119907 |
| 17 Finland |
p.Lys1729dup ^ | c.5186_5188dupAGA | Three over 3 generations | Early childhood with delay in walking walker | Y | N | Neck flexor weakness | Mild calf hypertrophy | SCV000119908 |
| 18 UK |
p.Leu1793del ^ | c.5378_5380delTGC | One | Mildly floppy baby, walking delayed til 18 months Presented with dilated cardiomyopathy aged 18 months | Y | Y | Hip girdle, with Trendelenburg gait | - | SCV000119909 |
| 19 Israel |
p.Glu1801Lys | c.5401G>A | Two, single generation | Delayed walking (20 months) and foot drop | Y by 6 years | N by 23 years | All lower limb muscles 4/5, dorsiflexion 1/5 | High arched palate | SCV000119910 |
| 20 USA |
p.Glu1914Lys ^ | c.5740G>A | One | Born at 33 weeks with hydrops fetalis Dilated cardiomyopathy and pulmonary hypertension at birth | Y by 3.5 years | - | Proximal and distal weakness | Diffuse hypotonia, microcephaly | SCV000119911 |
| 21 USA |
p.Glu1914Lys ^ | c.5740G>A | One | 8 weeks of life with dilated cardiomyopathy | Toe walks | N by 5 years | Diffuse hypotonia, poor endurance, neck flexion | Borderline microcephaly | SCV000119911 |
Y = yes, N = no, TA = tendo Achilles,
^
= novel mutation, not previously described,
*
MYH7 cDNA Accession number used = NM_000257.2