Supplemental data

GFPT1-Myasthenia: Clinical, Structural, and Electrophysiologic Heterogeneity.

Duygu Selcen MD1, Xin-Ming Shen PhD1, Margherita Milone MD, PhD1, Joan Brengman BS1, Kinji Ohno MD, PhD2, Feza Deymeer MD3, Richard Finkel MD4, Julie Rowin MD5, Andrew G. Engel MD1

Contents

Table e-1

Table e-2

Figure e-1

Figure e-2

Figure e-3

Table e-1. Clinical features and response to therapy

Patient no, sex, age
at onset, age at diagnosis of CMS, age when biopsied, age when examined / Family history / Presenting symptoms / Shoulder girdle weakness / Distal upper extremity weakness / Pelvic girdle weakness / Distal lower extremity weakness / Respiratory muscle weakness / Progressive course / Therapy / Maximal observed
EMG decrement at 2 Hz / Muscle biopsy
1. M, infancy, 16 y, 16 y, 16 y, 32 y / - / Poor cry, apneic spells / ++ / Digit extensors, ++ / ++ / Ant. tibial and toe extensors ++ / - / Yes / Pyridostigmine,
3,4-DAP / 45%, deltoid
26%, ant. tibial / Small tubular aggregates.
2. F, 8 y, 12 y, 17 y, 24 y / One affected sister / Difficulty climbing steps / ++ / Ant. forearm and small hand muscles,
++/+++ / ++/+++ / Ant. tibial and peroneal, ++ / - / Yes / Pyridostigmine,
3,4-DAP / 50%, ant. tibial
57%, trapezius / Type 1 fiber preponderance and smallness. Small
tubular aggregates.
3. F, 12 y,
20 y, 65 y, 69 y / Two affected brothers / Unable to squat / ++/+++ / Forearm extensors and small hand muscles, +/++ / +++ / Ant. tibial, ++ / - / Yes / Pyridostigmine,
3,4-DAP / 30%, ant. tibial / Type 1 fiber preponderance.
No tubular aggregates.
4. M, 19 y, 56 y, 56 y, 56 y / Two affected brothers / ++/+++ / Small hand muscles, + / ++ / Ant. tibial, ++/+++ / - / Yes / Pyridostigmine, ephedrine / 74%, biceps
83%, ant. tibial / Small vacuoles near endplates. Large
tubular aggregates.
5. M, 12 y, 12 y, 47 y, 49 y / One affected brother / Unable to keep up with peers / ++ / Forearm extensors, + / ++ / Ant. tibial, ± / + / Yes but mild / Pyridostigmine,
3,4-DAP, albuterol / 15%, trapezius / No tubular aggregates.
6. F, in utero, 1 month, 4 y, 6 y / Mother : high titer AChR antibodies but no symptoms / Hypotonia, arthrogryposis, weakness of all except the ocular muscles / +++ / +++ / +++ / +++ / +++ / Yes / Limited response to pyridostigmine,
3,4-DAP / 26%, ant. tibial / Vacuoles,
regenerating and necrotic fibers, type 1 fiber preponderance. Small tubular aggregates.
7. M, 10 y, 18 y, 14 y, 30 y / -- / Difficulty climbing steps / ++ / Forearm extensors, small hand muscles, + / ++ / Ant. tibial and toe extensors, + / - / Mild / Pyridostigmine / 30%, trapezius
30%, ant. tibial / Tubular aggregates
8. F, 9 y, 64 y, 64 y, 66 y / Usher syndrome / Difficulty walking / ++/+++ / + / ++ / + / Yes / Pyridostigmine / 40%, trapezius
30%, ant. tibial / Vacuoles; small tubular aggregates.

Table e-1, continued. Clinical features and response to therapy

9. M, 4 y, 9 y, 8 y, 14 y
Also has Asperger syndrome and congenital aortic stenosis. / One affected sister; 2 siblings with learning disability / Difficulty walking, clumsy / +/++ / - / ++ / Ant. tibial, + / - / No / Pyridostigmine,
3,4-DAP / 16%, trapezius / Tubular aggregates.
10. M, 3 y, 15 y, no biopsy, 25y. Also has high myopia. / Consang. parents; two affected uncles also have high myopia / Frequent falling, difficulty climbing stairs,
unable to keep up with peers / ++/+++ / + / ++/+++ / + / - / Yes / Pyridostigmine / 10%, abductor digiti minimi / ND
11. M, 15y, 21 y, no biopsy, 27 y / Consang. parents / Difficulty climbing stairs, easy fatigability / ++/+++ / + / ++/+++ / + / - / Yes / Pyridostigmine / 40%, extensor digitorum brevis / ND

-, absent; ±, trace; +, mild; ++, moderate; +++, marked. Abbreviations: ab, antibody; CMS, congenital myasthenic syndrome; Consang, consanguineous, ND, not done.

Table e-2 Endplate morphometry in 6 patients and 13 controls

Patient 1
(38 regions) / Patient 2
(24 regions) / Patient 3
(34 regions) / Patient 4
(30 regions) / Patient 5
(29 regions) / Patient 6
(15 regions) / 13 Controls
(45-61 regions)
Nerve terminal area (mm2)
P / 2.08 ± 0.23
<0.001 / 1.93 ± 0.21
<0.005 / 1.91 ± 0.28
<0.001 / 2.21 ± 1.17
<0.005 / 3.79 ± 0.76
NS / 1.32 ± 0.22
<0.005 / 3.88 ± 0.39
Postsynaptic area (mm2)
P / 4.71 ± 0.35
<0.001 / 5.83 ± 0.37
<0.001 / 7.51 ± 0.69
<0.05 / 6.24 ± 0.78
<0.005 / 10.57 ± 1.04
NS / 5.69 ± 0.97
<0.01 / 9.89 ± 0.81
Postsynaptic membrane length (mm)
P / 16 ± 1.39
<0.001 / 21.2 ± 1.51
<0.001 / 33.27 ± 2.72
<0.005 / 30.87 ± 2.48
<0.005 / 52.86 ± 8.51
NS / 19.96 ± 2.55
<0.001 / 52.74 ± 5.16
Postsynaptic membrane density
P / 3.34 ± 0.17
<0.001 / 3.72 ± 0.22
<0.001 / 4.57 ± 0.20
<0.001 / 4.91 ± 0.17
<0.05 / 4.97 ± 0.20
<0.05 / 4.34 ± 0.61
<0.02 / 5.67 ± 0.23

Values indicate mean ± SE. More than one region can be present at an endplate.


Figure e-1

Figure e-2

Rimmed vacuoles in Patient 8

Figure e-3