Neurology -- Correspondence for Wong et al., 65 (9) 1465-1466

Correspondence published:

Stiff child syndrome with mutation of DYT1 gene: Paul E Greene, William Dauer, MD, New York, NY (29 December 2005)

Reply from the author: Virginia Wong (29 December 2005)

Stiff child syndrome with mutation of DYT1 gene 29 December 2005

Paul E Greene,
Columbia University
710 West 168 Street, New York, NY 10032,
William Dauer, MD, New York, NY
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Re: Stiff child syndrome with mutation of DYT1 gene

greene{at}neuro.columbia.edu Paul E Greene, et al.

We were intrigued by the report of a boy with DYT1 presenting as stiff person syndrome (SPS). [1] However, the videotape seems to be consistent with painful DYT1-type dystonia. The authors diagnosed SPS because of painful spasms lasting hours, triggered by a variety of stimuli and improved after plasmapheresis. Unlike typical SPS (or the variant stiff-limb syndrome), in between spasms there was dystonic posturing and no abnormal motor unit activity. The absence of anti-GAD antibodies is against the diagnosis of SPS, but hardly definitive. [2] Painful limb dystonia is uncommon in DYT1, but not unheard of. In its most extreme form, a state of continuous or near continuous, painful dystonic spasms has been termed “dystonic storm” and has been reported several times in DYT1 dystonia. [3,4] The juvenile onset of dystonia in the legs is also typical of the disease.
The authors conclude that the phenotypic heterogeneity of DYT1 might include an SPS-like picture, or that their patient might have an incidental and clinically silent DYT1 mutation. Based on the video, we suggest an alternative conclusion: that their patient had a typical, albeit severe, manifestation of DYT1 dystonia. Other conditions have been mistaken for SPS. It is now widely recognized that many, if not all, infants with stimulus-evoked stiffness have hyperekplexia, not an infantile variant of SPS. [5]
Except in the presence of dystonic posturing, we believe screening for DYT1 in all children with muscle stiffness, as the authors suggest, will be unproductive.
References
1. Wong VCN, Lam C-W, Fung CW. Stiff child syndrome with mutation of DYT1 gene. Neurology 2005;65:1465-1466.
2. Murinson BB. Stiff-person syndrome. Neurologist 2004;10:131-137.
3. Jankovic J, Penn AS. Severe dystonia and myoglobinuria. Neurology 1982;32:1195-1197.
4. Dalvi A, Fahn S, Ford B. Intrathecal baclofen in the treatment of dystonic storm. Mov Disord 1998;13:611-612.
5. Cioni G, Biagioni E, Bottai P, Castellacci AM, Paolicelli PB. Hyperekplexia and stiff-baby syndrome: an identical neurological disorder?. Italian Journal of Neurological Sciences 1993;14:145-152.

Reply from the author 29 December 2005

Virginia Wong,
Division of Neurodevelopmental Pediatrics, Department of Pediatrics and Adolescent Medicine
The University of Hong Kong, Hong Kong, China
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Re: Reply from the author

vcnwong{at}hku.hk Virginia Wong

We thank Greene et al for their comments. The initial diagnosis was difficult in this case. At four years old, this boy had an onset of ankle stiffness, then gradual appearance of severe muscle stiffness, painful spasms and dystonia 2 years later. A diagnosis of SM/SPS rather than ITS was possible considering the subsequent EMG findings with continuous motor unit activity during spasms (and abolition with anesthesia) and positive anti-GAD antibodies in his insulin-dependent diabetes mellitus (IDDM) sister. [1]
We also presented this case at the International Movement Disorder Conference in New Orleans (2005) and the comments of various experts including Professor Stanley Fahn were helpful in preparing this paper.
The detection of DYT1 mutation in this boy and his asymptomatic mother might be a coincidence. There is incomplete penetrance of only 30-40% in patients with ITD and the phenotype of ITD has been widely recognized since the detection of DYT1 mutation in 1997. [6] Therefore, a positive differentiation is not realistic unless a sensitive and specific laboratory test is available to differentiate all diseases with dystonia as the major feature. I would suggest these diseases belong to different severity of a spectrum of disorder.
As in other diseases with known mutation and genotypic-phenotypic variation, a consortium of experts in SM/SPS and dystonia is needed to delineate the diagnostic checklist, both clinically and genetically, in order to benefit clinicians who are treating challenging cases. [7,8]
References
6. Bressman S. Dystonia Genotypes, Phenotypes, and Classification, in Advances in Neurology: Dystonia 4, H.M. Fahn S, DeLong MR, Editor. 2004, Lippincott Williams and Wilkins. p. 101-107.
7. Meinck, H.T., PD, Stiff Man Syndrome and Related Conditions. Movement Disorders, 2002. 17(5): p. 853-866.
8.Bressman, S.S., C; Raymond, D; de Leon, D; Klein, C; Kramer, PL; Brin, MF; Fahn, S; Breakefield, X; Ozelius, LJ; Risch, NJ, The DYT 1 phenotype and guidelines for diagnostic testing. Neurology, 2000. 54(9): p. 1746-1753.
The author reports no conflicts of interest.