Juvenile Huntington’s disease

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Juvenile Huntington’s disease (JHD) manifests in 1st–2nd decades of life and accounts for 2–9% of all cases of Huntington’s disease; its pathogenic mechanisms are related to genetic anticipation and imprinting. Typical features of JHD are akinesia and rigidity, and paternal inheritance and huntingtin mutations with particularly large number of CAG repeats (> 60); however, atypical cases exist, and maternal inheritance is possible. We report 6 families with 7 JHD cases confirmed by DNA testing; 4 patients, including two brothers, were clinicallyexamined. Three patients, one of the brothers among them, had an akinetic-rigid form with onset at 7–8 years; in the second brother the disease manifested at 20 years as a hyperkinetic form of the disease without dementia. This patient had mutation with 57 CAG repeats, while in the rest six patients the number ofrepeat copies varied from 63 to 81. All cases were familial, and anticipation in families was evident; in one child with JHD the disease manifested 4–5 years earlier than in the father, and in another family grandfather first noticed symptoms at 60 years, 6years after the JHD onset in his granddaughter. Such cases mask’ dominant inheritance and complicate the diagnosis. Three families showed rare maternal transmission of JHD: one of the affected mothers had JHD, and in two mothers the disease developed at 27–30 years and lasted for 3–9 years. In 4 clinically examined patients, JHD was supposed 7–18 years after its onset which shows underestimation of the disease in practice. JHD should be considered even in seemingly nonfamilial cases, and DNA testing for huntingtin mutations should be used more widely.


About the authors

Galina E. Rudenskaya

Research Centre for Medical Genetics

Author for correspondence.
Email: rudenskaya@med-gen.ru
Russian Federation, Moscow

D. A. Savvin

Russian State Pediatrics Hospital

Email: rudenskaya@med-gen.ru
Russian Federation, Moscow

V. P. Fedotov

Voronezh Genetic Counseling Department

Email: rudenskaya@med-gen.ru
Russian Federation, Voronezh

S. A. Kurbatov

Voronezh Genetic Counseling Department

Email: rudenskaya@med-gen.ru
Russian Federation, Voronezh

A. V. Polyakov

Research Center for Medical Genetics

Email: rudenskaya@med-gen.ru
Russian Federation, Moscow

N. M. Galeeva

Research Center for Medical Genetics

Email: rudenskaya@med-gen.ru
Russian Federation, Moscow


  1. Иллариошкин С.Н. Конформационные болезни мозга. М.: Янус-К, 2003.
  2. Клюшников С.А., Иллариошкин С.Н., Иванова-Смоленская И.А. Молекулярный анализ полиглутаминовых заболеваний в России. В кн.: Иллариошкин С.Н., Яхно Н.Н. (ред.). Болезнь Паркинсона и расстройства движений: Руководcтво для врачей по матер. I Национального конгр. М., 2008: 69–75.
  3. Клюшников С.А., Иллариошкин С. Н., Устюжанина Е.К. и др. Агенезия мозолистого тела у пациента с хореей Гентингтона. Атмосфера. Нервные болезни, 2006: 4 (www.atmosphere-ph.ru).
  4. Руденская Г.Е. Наследственные болезни нервной системы в российских и среднеазиатских популяциях: клинико-генетико- эпидемиологическое исследование: Автореф. дис. … докт. мед. наук. М., 1998.
  5. Юдина Г.К., Соловых Н.Н., Шоломов И.И. Клинико-генетическая характеристика наследственных экстрапирамидных заболеваний в Саратовской области. Журн. неврол. и психиатрии им. С.С. Корсакова 2005; 5: 52–55.
  6. Cannella M., Gellera C., Maglione V. et al. The gender effect in juvenile Huntington disease patients of Italian origin. Am. J. Med. Genet. 2004; 125: 92–98.
  7. Gambardella A., Muglia M., Labate A. et al. Juvenile Huntington’s disease presenting as progressive myoclonic epilepsy. Neurol. 2001; 57: 708–711.
  8. Gayán J., Brocklebank D., Andresen J. et al. Genomewide linkage scan reveals novel loci modifying age of onset of Huntington’s disease in the Venezuelan HD kindreds. Genet. Epidemiol. 2008; 32: 445–453.
  9. Gencik M., Hammans C., Strehl H. et al. Chorea Huntington: a rare case with childhood onset. Neuroped. 2002; 33: 90–92.
  10. Genetic testing in asymptomatic minors: recommendations of the European Society of Human Genetics (ESHG). Eur. J. Hum. Genet. 2009; 17: 720–721.
  11. Kartsaki E., Spanaki C., Tzagournissakis M. et al. Late-onset and typical Huntington disease families from Crete have distinct genetic origins. Int. J. Mol. Med. 2006; 17: 335–346.
  12. Laccone F., Christian W. A recurrent expansion of a maternal allele with 36 CAG repeats causes Huntington disease in two sisters. Am. J. Hum. Genet. 2000; 66: 1145–1148.
  13. Landau M., Cannard K. EEG characteristics in juvenile Huntington’s disease: a case report and review of the literature. Epileptic Disord. 2003; 5: 145-148.
  14. Li J., Hayden M., Almqvist E. et al. A genome scan for modifiers of age at onset in Huntington disease: The HD MAPS study. Am. J. Hum. Genet. 2003; 73: 682–687.
  15. Liu Y., Shen Y., Li H. et al. Intergeneration CAG expansion in a Wuhan juvenile-onset Huntington disease family. Neurosci. Bull. 2007; 23: 198–202.
  16. Metzger S., Rong J., Nguyen H. et al. Huntingtin-associated protein- 1 is a modifier of the age-at-onset of Huntington’s disease. Hum. Mol. Genet. 2008; 17: 1137–1146.
  17. Milunsky J., Maher T., Loose B. et al. XL PCR for the detection of large trinucleotide expansions in juvenile Huntington’s disease. Clin. Genet. 2003; 64: 70–73.
  18. Nahhas F., Garbern J., Krajewski K. et al. Juvenile onset Huntington disease resulting from a very large maternal expansion. Am. J. Med. Genet. A. 2005; 137A: 328–331.
  19. Nance M., Mathias-Hagen V., Breningstall G. et al. Analysis of a very large trinucleotide repeat in a patient with juvenile Huntington’s disease. Neurol. 1999; 52: 392–394.
  20. Papapetropoulos S., Lopez-Alberola R., Baumbach L. et al. Case of maternally transmitted juvenile Huntington’s disease with a very large trinucleotide repeat. Mov. Disord. 2005; 20: 1380–1383.
  21. Rasmussen A., Macias R., Yescas P. et al. Huntington disease in children: genotype-phenotype correlation. Neuroped. 2000; 31: 190–194.
  22. Ribaï P., Nguyen K., Hahn-Barma V. et al. Psychiatric and cognitive difficulties as indicators of juvenile Huntington disease onset in 29 patients. Arch. Neurol. 2007; 64: 813–819.
  23. Ruocco H., Lopes-Cendes I., Laurito T. et al. Clinical presentation of juvenile Huntington disease. Arq. Neuropsiquiatr. 2006; 64: 5–9.
  24. Sakazume S., Yoshinari S., Oguma E. et al. A patient with early onset Huntington disease and severe cerebellar atrophy. Am. J. Med. Genet. 2009; 149A: 598–601.
  25. Sathasivam K., Amaechi I., Mangiarini L., Bates G. Identification of an HD patient with a (CAG)180 repeat expansion and the propagation of highly expanded CGA-repeats in lambda phage. Hum. Genet. 1997; 99: 692–695.
  26. Schapiro M., Cecil K., Doescher J. et al. MR imaging and spectroscopy in juvenile Huntington disease. Pediatr. Radiol. 2004; 34: 640–643.
  27. Seneca S., Fagnart D., Keymolen K. et al. Early onset Huntington disease: a neuronal degeneration syndrome. Eur. J. Pediatr. 2004; 163: 717–721.
  28. Siesling S., Vegter-van der Vlis M., Roos R. Juvenile Huntington disease in the Netherlands. Pediatr. Neurol. 1997; 17: 37-43.
  29. Taherzadeh-Fard E., Saft C., Andrich J. et al. PGC-1alpha as modifier of onset age in Huntington disease. Mol. Neurodegener. 2009; 4: 10–16.
  30. Tang Y., Wang Y., Yang P. et al. Intergeneration CAG expansion and contraction in a Chinese HD family. Am. J. Med. Genet. 2006; 141B: 242–244.
  31. Ulrich N., Riviello J., Darras B., Donner E. Electroencephalographic correlate of juvenile Huntington disease. J. Child Neurol. 2004; 19: 431–543.
  32. Waugh J., Miller V., Chudnow R., Dowling M. Juvenile Huntington disease exacerbated by methylphenidate: case report. J. Child Neurol. 2008; 23: 807–809.
  33. Wexler N., Lorimer J., Porter J. et al. Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington’s disease age of onset. Proc. Natl. Acad. Sci. USA 2004; 101.
  34. Wheeler V., Persichetti F., McNeil S. et al. Factors associated with HD CAG repeat instability in Huntington disease. J. Med. Genet. 2007; 44: 695–701.
  35. Wojaczyńska-Stanek K., Adamek D., Marszał E., Hoffman- Zacharska D. Huntington disease in a 9-year-old boy: clinical course and neuropathologic examination. J. Child Neurol. 2006; 21: 1068–1073.
  36. Xing S., Chen L., Chen X. et al. Excessive blinking as an initial manifestation of juvenile Huntington’s disease. Neurol. Sci. 2008; 29: 275–277.
  37. Yoon G., Kramer J., Zanko A. et al. Speech and language delay are early manifestations of juvenile-onset Huntington disease. Neurol. 2006; 67: 1265–1267.

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Copyright (c) 2010 Rudenskaya G.E., Savvin D.A., Fedotov V.P., Kurbatov S.A., Polyakov A.V., Galeeva N.M.

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