TY - JOUR
T1 - Congenital myasthenic syndromes in adult neurology clinic
T2 - A long road to diagnosis and therapy
AU - Kao, Justin C.
AU - Milone, Margherita
AU - Selcen, Duygu
AU - Shen, Xin Ming
AU - Engel, Andrew G.
AU - Liewluck, Teerin
N1 - Publisher Copyright:
Copyright © 2018 American Academy of Neurology.
PY - 2018/11/6
Y1 - 2018/11/6
N2 - Objective To investigate the diagnostic challenges of congenital myasthenic syndromes (CMS) in adult neuromuscular practice. Methods We searched the Mayo Clinic database for patients with CMS diagnosed in adulthood in the neuromuscular clinic between 2000 and 2016. Clinical, laboratory, and electrodiagnostic data were reviewed. Results We identified 34 patients with CMS, 30 of whom had a molecular diagnosis (14 DOK7, 6 RAPSN, 2 LRP4, 2 COLQ, 2 slow-channel syndrome, 1 primary acetylcholine receptor deficiency, 1 AGRN, 1 GFPT1, and 1 SCN4A). Ophthalmoparesis was often mild and present in 13 patients. Predominant limb-girdle weakness occurred in 19 patients. Two patients had only ptosis. Age at onset ranged from birth to 39 years (median 5 years). The median time from onset to diagnosis was 26 years (range 4-56 years). Thirteen patients had affected family members. Fatigable weakness was present when examined. Creatine kinase was elevated in 4 of 23 patients (range 1.2-4.2 times the upper limit of normal). Repetitive nerve stimulation revealed a decrement in 30 patients. Thirty-two patients were previously misdiagnosed with seronegative myasthenia gravis (n = 16), muscle diseases (n = 15), weakness of undetermined cause (n = 8), and others (n = 4). Fifteen patients received immunotherapy or thymectomy without benefits. Fourteen of the 25 patients receiving pyridostigmine did not improve or worsen. Conclusion Misdiagnosis occurred in 94% of the adult patients with CMS and causes a median diagnostic delay of nearly 3 decades from symptom onset. Seronegative myasthenia gravis and muscle diseases were the 2 most common misdiagnoses, which led to treatment delay and unnecessary exposure to immunotherapy, thymectomy, or muscle biopsy.
AB - Objective To investigate the diagnostic challenges of congenital myasthenic syndromes (CMS) in adult neuromuscular practice. Methods We searched the Mayo Clinic database for patients with CMS diagnosed in adulthood in the neuromuscular clinic between 2000 and 2016. Clinical, laboratory, and electrodiagnostic data were reviewed. Results We identified 34 patients with CMS, 30 of whom had a molecular diagnosis (14 DOK7, 6 RAPSN, 2 LRP4, 2 COLQ, 2 slow-channel syndrome, 1 primary acetylcholine receptor deficiency, 1 AGRN, 1 GFPT1, and 1 SCN4A). Ophthalmoparesis was often mild and present in 13 patients. Predominant limb-girdle weakness occurred in 19 patients. Two patients had only ptosis. Age at onset ranged from birth to 39 years (median 5 years). The median time from onset to diagnosis was 26 years (range 4-56 years). Thirteen patients had affected family members. Fatigable weakness was present when examined. Creatine kinase was elevated in 4 of 23 patients (range 1.2-4.2 times the upper limit of normal). Repetitive nerve stimulation revealed a decrement in 30 patients. Thirty-two patients were previously misdiagnosed with seronegative myasthenia gravis (n = 16), muscle diseases (n = 15), weakness of undetermined cause (n = 8), and others (n = 4). Fifteen patients received immunotherapy or thymectomy without benefits. Fourteen of the 25 patients receiving pyridostigmine did not improve or worsen. Conclusion Misdiagnosis occurred in 94% of the adult patients with CMS and causes a median diagnostic delay of nearly 3 decades from symptom onset. Seronegative myasthenia gravis and muscle diseases were the 2 most common misdiagnoses, which led to treatment delay and unnecessary exposure to immunotherapy, thymectomy, or muscle biopsy.
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U2 - 10.1212/WNL.0000000000006478
DO - 10.1212/WNL.0000000000006478
M3 - Article
C2 - 30291185
AN - SCOPUS:85056262457
SN - 0028-3878
VL - 91
SP - E1770-E1777
JO - Neurology
JF - Neurology
IS - 19
ER -