Dopamine-Responsive Dystonia Clinical Presentation

  • Author: Nirjal K Nikhar, MD, FRCP; Chief Editor: Amy Kao, MD   more...
 
Updated: Feb 27, 2012
 

History

The most common presenting symptom of dopamine-responsive dystonia (DRD) is a gait disturbance. These patients may be misdiagnosed as having cerebral palsy.

Typically, the dystonia starts in 1 lower limb (with evening exacerbation), resulting in a tiptoe (equinus) walking pattern. Early in the disease course, patients are symptom free in the morning. Diurnal aggravation of symptoms depends more on the number of waking hours than on physical activity.

The disease progresses markedly in the first 15 years, with postural dystonia progressing to all 4 limbs (even in the morning) by the end of the second decade. Progression slows in the third decade and plateaus thereafter.[19]

Variations in DRD clinical presentation have been described. These include trunk and focal dystonias, such as spasmodic torticollis, oromandibular dystonia, and writer's cramp.[4, 20, 21]

Clinical features described here are those characterized for dominant DRD with GCH1 gene mutations. Some of the TH-deficient patients have predominant parkinsonism features without diurnal fluctuations.[14, 22, 23]

The onset and clinical severity of disease are variable, sometimes even within a single family, due to putative gender effects on allele penetrance.[24]

Next

Physical Examination

The patient may have stunted growth with short stature if the disease was not treated in childhood. This improves if treatment is started early in the disease course. The dystonia is variable in severity, depending on the duration of disease prior to treatment.

Gait disturbance is characterized by leg stiffness and a tendency to walk in an equinus posture. The great toe is dorsiflexed. Gait tends to worsen later in the day. With increasing age and without treatment, dystonia spreads to involve the trunk and all 4 extremities.

Postural tremor, which is not observed in childhood, appears after the third decade. Resting tremor and rigidity are absent, and interlimb coordination is preserved (even in advanced cases).

Bradykinesia may develop. This is not due to failure of initiation and poverty of movement as in parkinsonism; rather, it is due to failure of reciprocal innervation resulting from the dystonia.

Muscle tone is increased and deep tendon reflexes are exaggerated (with ankle clonus). The plantar reflex is flexor, although striatal toe is common.[19]

Clinical manifestations have significant heterogeneity, with intrafamilial variation in clinical phenotype, including the degree of levodopa responsiveness.[25]

Previous
Proceed to Differential Diagnoses
 
 
Contributor Information and Disclosures
Author

Nirjal K Nikhar, MD, FRCP  Private Practice

Nirjal K Nikhar, MD, FRCP is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.

Coauthor(s)

Haresh Mani, MD  Assistant Professor, Department of Pathology, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine

Disclosure: Nothing to disclose.

Syed M S Ahmed, MD  Neurologist and Sleep Specialist, The Sleep Disorder Clinic of Washington, The Neurology Clinic of Washington; Staff Attending in Neurology and Sleep Medicine, Montgomery General Hospital; Staff Attending in Neurology and Sleep Medicine, Suburban Hospital

Syed M S Ahmed, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, and Maryland State Medical Society

Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD  Attending Neurologist, Children's National Medical Center

Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, and Child Neurology Society

Disclosure: Nothing to disclose.

Additional Contributors

Nestor Galvez-Jimenez, MD, MSc, MHA Chairman, Department of Neurology, Program Director, Movement Disorders, Department of Neurology, Division of Medicine, Cleveland Clinic Florida

Nestor Galvez-Jimenez, MD, MSc, MHA is a member of the following medical societies: American Academy of Neurology, American College of Physicians, and Movement Disorders Society

Disclosure: Nothing to disclose.

Ann M Neumeyer, MD Clinic Director, Instructor, Departments of Neurology and Pediatrics, Massachusetts General Hospital, Harvard Medical School

Ann M Neumeyer, MD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, and Massachusetts Medical Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Reference Salary Employment

References

  1. Segawa M, Hosaka A, Miyagawa F, Nomura Y, Imai H. Hereditary progressive dystonia with marked diurnal fluctuation. Adv Neurol. 1976;14:215-33. [Medline].

  2. Chen RS, Huang CC, Lu CS. Dopa-responsive dystonia: clinical and family study in Taiwanese. Clin Neurol Neurosurg. Feb 1996;98(1):43-6. [Medline].

  3. Nygaard TG. Dopa-responsive dystonia. Curr Opin Neurol. Aug 1995;8(4):310-3. [Medline].

  4. Maruta K, Okamoto S, Takegami T. [A form of dopa-responsive dystonia of late onset with diurnal fluctuations]. Rinsho Shinkeigaku. Mar 1993;33(3):341-3. [Medline].

  5. Nomura Y. [The clinical characteristics of involuntary movements in childhood]. No To Hattatsu. May 1997;29(3):199-205. [Medline].

  6. Ludecke B, Dworniczak B, Bartholome K. A point mutation in the tyrosine hydroxylase gene associated with Segawa's syndrome. Hum Genet. Jan 1995;95(1):123-5. [Medline].

  7. Nygaard TG, Wilhelmsen KC, Risch NJ, Brown DL, Trugman JM, Gilliam TC. Linkage mapping of dopa-responsive dystonia (DRD) to chromosome 14q. Nat Genet. Dec 1993;5(4):386-91. [Medline].

  8. Ichinose H, Ohye T, Takahashi E, Seki N, Hori T, Segawa M. Hereditary progressive dystonia with marked diurnal fluctuation caused by mutations in the GTP cyclohydrolase I gene. Nat Genet. Nov 1994;8(3):236-42. [Medline].

  9. Thony B, Blau N. Mutations in the BH4-metabolizing genes GTP cyclohydrolase I, 6-pyruvoyl-tetrahydropterin synthase, sepiapterin reductase, carbinolamine-4a-dehydratase, and dihydropteridine reductase. Hum Mutat. Sep 2006;27(9):870-8. [Medline].

  10. Gasser T. Idiopathic, myoclonic and Dopa-responsive dystonia. Curr Opin Neurol. Aug 1997;10(4):357-62. [Medline].

  11. Bartholome K, Ludecke B. Mutations in the tyrosine hydroxylase gene cause various forms of L-dopa-responsive dystonia. Adv Pharmacol. 1998;42:48-9. [Medline].

  12. Liu X, Zhang SS, Fang DF, Ma MY, Guo XY, Yang Y, et al. GCH1 mutation and clinical study of Chinese patients with dopa-responsive dystonia. Mov Disord. Mar 15 2010;25(4):447-51. [Medline].

  13. Neville BG, Parascandalo R, Farrugia R, Felice A. Sepiapterin reductase deficiency: a congenital dopa-responsive motor and cognitive disorder. Brain. Oct 2005;128(Pt 10):2291-6. [Medline].

  14. Furukawa Y, Kish SJ. Dopa-responsive dystonia: recent advances and remaining issues to be addressed. Mov Disord. Sep 1999;14(5):709-15. [Medline].

  15. Takahashi H, Levine RA, Galloway MP, Snow BJ, Calne DB, Nygaard TG. Biochemical and fluorodopa positron emission tomographic findings in an asymptomatic carrier of the gene for dopa-responsive dystonia. Ann Neurol. Mar 1994;35(3):354-6. [Medline].

  16. Hagenah J, Saunders-Pullman R, Hedrich K, Kabakci K, Habermann K, Wiegers K. High mutation rate in dopa-responsive dystonia: detection with comprehensive GCHI screening. Neurology. Mar 8 2005;64(5):908-11. [Medline].

  17. de la Fuente-Fernandez R, Schulzer M, Mak E, Calne DB, Stoessl AJ. Presynaptic mechanisms of motor fluctuations in Parkinson's disease: a probabilistic model. Brain. Apr 2004;127(Pt 4):888-99. [Medline].

  18. Furukawa Y, Lang AE, Trugman JM, Bird TD, Hunter A, Sadeh M. Gender-related penetrance and de novo GTP-cyclohydrolase I gene mutations in dopa-responsive dystonia. Neurology. Apr 1998;50(4):1015-20. [Medline].

  19. Segawa M, Nomura Y, Kase M. Diurnally fluctuating hereditary progressive dystonia. In: Handbook of Clinical Neurology, Extrapyramidal Disorders. Vol 5. Elsevier: Amsterdam; 1986:529-539.

  20. Deonna T, Roulet E, Ghika J, Zesiger P. Dopa-responsive childhood dystonia: a forme fruste with writer's cramp, triggered by exercise. Dev Med Child Neurol. Jan 1997;39(1):49-53. [Medline].

  21. Steinberger D, Topka H, Fischer D, Müller U. GCH1 mutation in a patient with adult-onset oromandibular dystonia. Neurology. Mar 10 1999;52(4):877-9. [Medline].

  22. Brautigam C, Wevers RA, Jansen RJ, Smeitink JA, de Rijk-van Andel JF, Gabreels FJ. Biochemical hallmarks of tyrosine hydroxylase deficiency. Clin Chem. Sep 1998;44(9):1897-904. [Medline].

  23. Ludecke B, Knappskog PM, Clayton PT, Surtees RA, Clelland JD, Heales SJ. Recessively inherited L-DOPA-responsive parkinsonism in infancy caused by a point mutation (L205P) in the tyrosine hydroxylase gene. Hum Mol Genet. Jul 1996;5(7):1023-8. [Medline].

  24. Cheyette BN, Cheyette SN, Cusmano-Ozog K, Enns GM. Dopa-responsive dystonia presenting as delayed and awkward gait. Pediatr Neurol. Apr 2008;38(4):273-5. [Medline].

  25. Robinson R, McCarthy GT, Bandmann O, Dobbie M, Surtees R, Wood NW. GTP cyclohydrolase deficiency; intrafamilial variation in clinical phenotype, including levodopa responsiveness. J Neurol Neurosurg Psychiatry. Jan 1999;66(1):86-9. [Medline].

  26. Segawa M, Nishiyama N, Nomura Y. DOPA-responsive dystonic parkinsonism--pathophysiologic considerations. Adv Neurol. 1999;80:389-400. [Medline].

  27. Yokochi M. Juvenile Parkinson's disease. Part I. Clinical aspects. Adv Neurol Sci. 1979;23:1060-1073.

  28. Jeon BS, Jeong JM, Park SS, Kim JM, Chang YS, Song HC. Dopamine transporter density measured by [123I]beta-CIT single-photon emission computed tomography is normal in dopa-responsive dystonia. Ann Neurol. Jun 1998;43(6):792-800. [Medline].

  29. Nygaard TG, Waran SP, Levine RA, Naini AB, Chutorian AM. Dopa-responsive dystonia simulating cerebral palsy. Pediatr Neurol. Oct 1994;11(3):236-40. [Medline].

  30. Fujita S, Shintaku H. Etiology and pteridine metabolism abnormality of hereditary progressive dystonia with marked diurnal fluctuation (HPD: Segawa disease). Med J Kushiro City Hosp. 1990;2:64-67.

  31. Segawa M, Nomura Y. Hereditary progressive dystonia with marked diurnal fluctuation. Pathophysiological importance of the age of onset. Adv Neurol. 1993;60:568-76. [Medline].

  32. Hyland K, Fryburg JS, Wilson WG, Bebin EM, Arnold LA, Gunasekera RS. Oral phenylalanine loading in dopa-responsive dystonia: a possible diagnostic test. Neurology. May 1997;48(5):1290-7. [Medline].

  33. Saunders-Pullman RJ, Raymond D, Hyland K, et al. Markers of disease in dopa-responsive dystonia. Mov Disord. 1998;13(suppl 2):285.

  34. Saunders-Pullman R, Blau N, Hyland K, Zschocke J, Nygaard T, Raymond D. Phenylalanine loading as a diagnostic test for DRD: interpreting the utility of the test. Mol Genet Metab. Nov 2004;83(3):207-12. [Medline].

  35. Furukawa Y, Shimadzu M, Rajput AH, Shimizu Y, Tagawa T, Mori H. GTP-cyclohydrolase I gene mutations in hereditary progressive amd dopa-responsive dystonia. Ann Neurol. May 1996;39(5):609-17. [Medline].

  36. Rajput AH, Gibb WR, Zhong XH, Shannak KS, Kish S, Chang LG. Dopa-responsive dystonia: pathological and biochemical observations in a case. Ann Neurol. Apr 1994;35(4):396-402. [Medline].

  37. Snow BJ, Okada A, Martin WRW. Positron emission tomography scanning in dopa-responsive dystonia, parkinsonism-dystonia, and young-onset parkinsonism. Hereditary progressive dystonia with marked diurnal fluctuation, carnforth, U.K,. 1993;181-186.

  38. Sawle GV, Leenders KL, Brooks DJ, Harwood G, Lees AJ, Frackowiak RS. Dopa-responsive dystonia: [18F]dopa positron emission tomography. Ann Neurol. Jul 1991;30(1):24-30. [Medline].

  39. Rinne JO, Iivanainen M, Metsahonkala L, Vainionpaa L, Paakkonen L, Nagren K. Striatal dopaminergic system in dopa-responsive dystonia: a multi-tracer PET study shows increased D2 receptors. J Neural Transm. Jan 2004;111(1):59-67. [Medline].

  40. Hwang WJ, Yao WJ, Wey SP, Ting G. Clinical and [99mTc]TRODAT-1/[123I]IBZM SPECT imaging findings in dopa-responsive dystonia. Eur Neurol. 2004;51(1):26-9. [Medline].

  41. Hsu KY, Kuo KN, Hsu RW. Correction of foot deformity by the Ilizarov method in a patient with Segawa disease. Clin Orthop Relat Res. May 1995;(314):199-202. [Medline].

  42. Thony B, Calvo AC, Scherer T, Svebak RM, Haavik J, Blau N. Tetrahydrobiopterin shows chaperone activity for tyrosine hydroxylase. J Neurochem. Jul 2008;106(2):672-81. [Medline].

  43. de la Fuente-Fernandez R. Drug-induced motor complications in dopa-responsive dystonia: implications for the pathogenesis of dyskinesias and motor fluctuations. Clin Neuropharmacol. Jul-Aug 1999;22(4):216-9. [Medline].

  44. Hwu WL, Wang PJ, Shen YZ. Hereditary progressive dystonia with marked diurnal fluctuation: report of a case. Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi. Jan-Feb 1989;30(1):46-51. [Medline].

  45. Gherpelli JL, Nagae LM, Diament A. DOPA-sensitive progressive dystonia of childhood with diurnal fluctuations of symptoms: a case report. Arq Neuropsiquiatr. Jun 1995;53(2):298-301. [Medline].

  46. Wang PJ, Ko YM, Young C, Hwu WL, Shen YZ. Hereditary progressive dystonia with marked diurnal fluctuation (Segawa syndrome) in Taiwan. Brain Dev. Mar-Apr 1994;16(2):126-31. [Medline].

  47. Ishida A, Takada G, Kobayashi Y, Toyoshima I, Takai K. Effect of tetrahydrobiopterin and 5-hydroxytryptophan on hereditary progressive dystonia with marked diurnal fluctuation: a suggestion of the serotonergic system involvement. Tohoku J Exp Med. Mar 1988;154(3):233-9. [Medline].

  48. Dewey RB Jr, Muenter MD, Kishore A, Snow BJ. Long-term follow-up of levodopa responsiveness in generalized dystonia. Arch Neurol. Oct 1998;55(10):1320-3. [Medline].

 
Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.