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The Natural History and Clinical Progression of Huntington’s Disease in Venezuela


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Dr. Juan Sanchez-Ramos's presentation for the Local Practitioner's Program at HSG 2015 on the natural history of Huntington disease in Venezuela.

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The Natural History and Clinical Progression of Huntington’s Disease in Venezuela

  1. 1. The Natural History and Clinical Progression of Huntington’s Disease in Venezuela Juan Sanchez-Ramos, PhD, MD Dept of Neurology, University of South Florida
  2. 2. George Huntington (1850-1916) “On Chorea” published at age 22 Nancy Wexler with affected child in Venezuela
  3. 3. • The Venezuelan HD kindreds first were described by a Venezuelan neurologist: Negrette, A. (1955) Corea de Huntington: Estudio de Una Sola Familia a Traves de Varias Genereaciones (Universidad de Zulia, Maracaibo, Venezuela). • An international, interdisciplinary team headed by Dr. Nancy Wexler has traveled annually to Venezuela since 1979, assessing these family members with an extensive and vigorous battery of neurological, psychiatric and cognitive tests • Diagnosis of clinically manifest HD (and age of onset) was determined by the appearance of specific motor abnormalities, characteristic of either the adult or juvenile form of the disorder. • To improve accuracy in determining diagnosis, affection status was only confirmed after three diagnoses were made, either by three different neurologists in the same year, or three diagnoses in subsequent years by the same or different neurologists. The Venezuela Kindred
  4. 4. Some of the Neurologists Who Examined Affected HD patients and those at risk in Venezuela
  5. 5. Venezuela Site of the “founders” off the HD Kindreds
  6. 6. • The Venezuelan HD kindreds comprise 18,149 individuals. There are 9,162 males, 8,256 females, and 731 individuals of unknown gender. Of these, 15,409 are living, and 78% are younger than age 40 years. • There are 83 independent kindreds with HD. The majority, 14,761 individuals, belong to the main kindred, tracing their origin to a single founder living in the early 1800s. The remaining 3,883 individuals form 82 kindreds of varying size. Most are quite large: three comprise between 200 and 600 people, and nine other kindreds each include between 100 and 199 individuals. • The full Venezuelan HD kindreds encompass 10 generations and 4,502 sibships, with an average size of 4.998 siblings and a range of 1 to 21 siblings. The kindreds contain the following pairs: 26,330 sibling, 25,252 parent-offspring, 33,534 grandparental, 97,870 avuncular, 8181 half-sibling, and 180,494 cousin. • Additionally, 3,783 individuals are founders, 12,626 people are considered nonfounders,
  7. 7. Age of Onset
  8. 8. Movement Disorders 5(2);93-99, 1990
  9. 9. Characteristics of the Movement Disorder •Most often hyperkinetic, choreiform •Dystonia, rigidity, akinesia supervene later in course •Rigidity, bradykinesia, tremor can be prominent in juvenile onset HD (<20 yrs age)
  10. 10. Movement Disorders 5(2);93-99, 1990
  11. 11. Movement Disorders 5(2);93-99, 1990
  12. 12. Summary • The existence of a large Venezuela HD kindred was brought to the attention of US researchers by Dr. Negrete and his students • Led to the Venezuela-USA Collaborative Research Project to discovery the gene, led by Dr. Nancy Wexler • The project was a big success because: • provided access to large numbers of tissue/blood samples from generations of clinically-manifest HD patients and those at risk. • This led to the identification of the HD gene (the first trinucleotide repeat expansion disease) • Allowed the study of the natural progression of the disease in patients who were un-medicated throughout the course of the illness.