We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Review |

Pharmacologic Treatment of Downstream of Tyrosine Kinase 7 Congenital Myasthenic Syndrome

Nanna Witting, MD, PhD1; John Vissing, MD, DMSci1
[+] Author Affiliations
1Neuromuscular Research Unit, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
JAMA Neurol. 2014;71(3):350-354. doi:10.1001/jamaneurol.2013.5590.
Text Size: A A A
Published online

Importance  Congenital myasthenic syndromes (CMSs) are increasingly recognized as causes of muscle fatigue and weakness. However, treatment of individual syndromes has been described only in small case series.

Objective  To analyze the information published thus far concerning the effect of pharmacologic treatment of one of the most common subtypes of CMS, downstream of tyrosine kinase 7 (DOK7) CMS.

Evidence Review  In a search of the PubMed database, we found 16 publications describing the response to medication in 122 individuals with DOK7 deficiency. The last search was performed August 15, 2013. If more than 1 article had been published by the same group, a comparison of the participants in the studies was made, and data appearing more than once were excluded.

Findings  Positive effects were observed in 6 of 66 patients who received an acetylcholinesterase inhibitor, 65 of 69 patients who received ephedrine or salbutamol, 18 of 29 who were given 3,4-diaminopyridine, and 13 of 16 individuals who received a combination of these drugs. Our analysis found no evidence that age at disease onset, age at treatment start, drug dosage, or mutation type influenced treatment results. The magnitude of treatment effect with ephedrine or salbutamol seems to increase gradually, peaking after approximately 6 to 8 months. Treatment with acetylcholinesterase inhibitors resulted in worsened conditions for most patients.

Conclusions and Relevance  This analysis suggests that (1) ephedrine or salbutamol is the first choice of treatment in DOK7 CMS; (2) 3,4-diaminopyridine may provide additional benefi; (3) it is never too late to initiate treatment; and (4) in contrast to acquired myasthenia gravis, treatment with acetylcholinesterase inhibitors should be avoided in DOK7 CMS.

Figures in this Article

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?


Place holder to copy figure label and caption
Effect of Drug Type, Age at Onset of Symptoms, and Age at Start of Medication Based on Review of the Literature

Each dot represents a person. ACEI indicates acetylcholinesterase inhibitor; DAP, 3,4-diaminopyridine; and E/S, ephedrine/salbutamol.

Graphic Jump Location




Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.


Some tools below are only available to our subscribers or users with an online account.

8 Citations

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles

Users' Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice, 3rd ed