This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
Mutations in the MFN2 gene, encoding mitofusin2, cause autosomal dominant axonal Charcot-Marie-Tooth type 2 (CMT2A, MIM: 608507).1 MFN2 mutations are also found in CMT2 subjects with optic atrophy2 or cognitive impairment.3 The sibship we studied comprised 3 affected and 3 apparently healthy individuals (figure e-1 on the Neurology® Web site at www.neurology.org).
Standard protocol approvals, registrations, and patient consents.
The study was approved by the institutional ethics committee. Written informed consent was obtained from all participants in the study.
Clinical cases and results.
For more information, see e-Methods. A 48-year-old woman presented with a 10-year history of progressive leg weakness, foot drop, hypotrophy, areflexia, intact sensation, and cognition. Neurophysiology (table e-1) revealed a severe axonal polyneuropathy. The sural nerve biopsy (figure e-2, A and B) showed reduced fiber densities, loss of large myelinated fibers, and marginal Wallerian degeneration. Teased fibers were thin, with shortened internodes, some ongoing remyelination, and no demyelination. She was wheelchair-bound within 1 year. At age 50, after colectomy, she developed a progressive brainstem syndrome with vomiting, nystagmus, chorea, clouded consciousness, and dysautonomia (hyperthermia, breathing irregularities). MRI showed diffuse T2 hyperintensities in the upper brainstem and periaqueductal gray (figure 1A). Blood and CSF examinations were unremarkable. The patient progressively worsened in spite of aggressive management, including thiamine supplementation, and died 7 days later. Brain pathology revealed symmetric vasculonecrotic lesions in the brainstem and the periaqueductal gray with small hemorrhagic component (figure e-2, C and D).
Figure 1 Neuroimaging and molecular data of index case
(A) Fluid-attenuated inversion recovery axial (a) and coronal (b) images of case II-7 2 days after onset of the encephalopathic symptoms. Symmetric high signal intensity alterations surround the aqueduct, involve the medial thalami, the mammillary bodies, and the tegmental area. (B) Sequence of the wild-type (WT) and mutated (Mut) MFN2 …
AAN Members
We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.
AAN Non-Member Subscribers
Purchase access
Letters: Rapid online correspondence
REQUIREMENTS
You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.
You May Also be Interested in
Long-term Safety and Efficacy of Avalglucosidase Alfa in Patients With Late-Onset Pompe Disease
Dr. Marianne de Visser and Dr. Maudy Theunissen