Huntington disease

Videos

Notes

Genetics

Genetics

Genetic disorders
Down syndrome (Trisomy 21)
Edwards syndrome (Trisomy 18)
Patau syndrome (Trisomy 13)
Fragile X syndrome
Huntington disease
Myotonic dystrophy
Friedreich ataxia
Turner syndrome
Klinefelter syndrome
Prader-Willi syndrome
Angelman syndrome
Beckwith-Wiedemann syndrome
Cri du chat syndrome
Williams syndrome
Alagille syndrome (NORD)
Achondroplasia
Polycystic kidney disease
Familial adenomatous polyposis
Familial hypercholesterolemia
Hereditary spherocytosis
Huntington disease
Li-Fraumeni syndrome
Marfan syndrome
Multiple endocrine neoplasia
Myotonic dystrophy
Neurofibromatosis
Tuberous sclerosis
von Hippel-Lindau disease
Albinism
Polycystic kidney disease
Cystic fibrosis
Friedreich ataxia
Gaucher disease (NORD)
Glycogen storage disease type I
Glycogen storage disease type II (NORD)
Glycogen storage disease type III
Glycogen storage disease type IV
Glycogen storage disease type V
Hemochromatosis
Mucopolysaccharide storage disease type 1 (Hurler syndrome) (NORD)
Krabbe disease
Leukodystrophy
Niemann-Pick disease types A and B (NORD)
Niemann-Pick disease type C
Primary ciliary dyskinesia
Phenylketonuria (NORD)
Sickle cell disease (NORD)
Tay-Sachs disease (NORD)
Alpha-thalassemia
Beta-thalassemia
Wilson disease
Fragile X syndrome
Alport syndrome
X-linked agammaglobulinemia
Fabry disease (NORD)
Glucose-6-phosphate dehydrogenase (G6PD) deficiency
Hemophilia
Mucopolysaccharide storage disease type 2 (Hunter syndrome) (NORD)
Lesch-Nyhan syndrome
Muscular dystrophy
Ornithine transcarbamylase deficiency
Wiskott-Aldrich syndrome
Mitochondrial myopathy
Autosomal trisomies: Pathology review
Muscular dystrophies and mitochondrial myopathies: Pathology review
Miscellaneous genetic disorders: Pathology review

Assessments
Huntington disease

Flashcards

0 / 16 complete

Questions

0 / 10 complete
High Yield Notes
5 pages
Flashcards

Huntington disease

16 flashcards
Preview

Huntington disease and other hyperkinetic disorders typically reflect a problem with the pathway of the basal ganglia.

Questions

USMLE® Step 1 style questions USMLE

9 questions

USMLE® Step 2 style questions USMLE

8 questions
Preview

A 52-year-old man comes to the clinic because of gradual cognitive decline. His 25-year-old daughter says, "he's changed these past few months. He is now very forgetful and is frequently agitated, which is not like the old him." He has a family history of cardiovascular disease, and his mother died due to rupture of an abdominal aortic aneurysm. He is diagnosed with Huntington disease. Which of the following most accurately describes this condition?

External References
Transcript

Contributors:

Philip Boone

Huntington disease, or HD, is a rare neurodegenerative disease that involves a repeated sequence of DNA that causes an abnormal protein to form, leading to abnormal movements and cognitive problems.

Huntington disease is an autosomal dominant genetic disorder, which means that one affected copy of a gene is enough to cause disease.

Affected people are typically present in each generation, because an affected person (male or female) has a 50% chance of passing on the affected gene to a child, which causes that child to have the disease.

In most people, a gene called huntingtin or HTT on chromosome 4, contains a triplet repeat, where the nucleotides C, A, and G are repeated 10-35 times in a row.

In people with Huntington disease, this repeat goes on for 36 or more times in a row.

CAG codes for the amino acid glutamine, so people with Huntington disease patients will have 36 or more glutamines in a row in the huntingtin protein.

So, in addition to being a triplet repeat disorder, HD is, more specifically, a “polyglutamine” disease.

The specific way in which extra glutamines causes HD symptoms isn’t fully worked out, but some clues are that the mutated protein aggregates within the neuronal cells of the caudate and putamen of the basal ganglia causing neuronal cell death.

Cell death might be related to excitotoxicity – which is excessive signaling of these neurons, which leads to high intracellular calcium.

The expanded CAG repeats not only affect the huntingtin protein – they affect DNA replication itself.

When copying the HTT gene, DNA polymerase can basically lose track of which CAG it’s on and accidently add extra CAGs.

Since as a zygote develops into a fetus and eventually into a full adult, by the time sperm and eggs are created, several dozen cell divisions, each with a round of DNA replication have taken place, and so there have already been ample opportunities for repeat expansion, and the more repeats that’re added, the more unstable it gets.

This expansion of the originally inherited gene means a child of a parent with HD can inherit even more CAG repeats than the parent did.

The higher the number of repeats in the protein, the earlier the age when a person starts having symptoms.

This phenomenon is called anticipation, which means that Huntington disease families often show earlier symptom onset with each generation.

Even repeats of 27-35 CAGs can expand occasionally; these are called “pre-mutation” alleles, since they don’t cause the disease, but they’re set-up for developing a mutation of 36 or more CAGs.