Can women inherit Huntington's disease?

Can Women Inherit Huntington's Disease?

Yes, women can inherit Huntington's disease (HD) as it is transmitted in an autosomal dominant manner, affecting both males and females equally. 1

Genetics of Huntington's Disease

Huntington's disease is caused by an abnormal expansion of CAG trinucleotide repeats in the Huntingtin gene (HTT) located on chromosome 4p16.3. This genetic mutation affects both sexes equally because:

• HD follows an autosomal dominant inheritance pattern 1
• The HTT gene is located on chromosome 4, which is an autosome (non-sex chromosome) 1
• Both men and women have two copies of chromosome 4 and can therefore inherit and transmit the mutation

CAG Repeat Expansion

The severity and age of onset of HD correlate with the number of CAG repeats:

• Normal individuals: 9-26 CAG repeats 1
• Mutable normal alleles: 27-35 CAG repeats (may expand in future generations but not associated with disease) 1
• Reduced penetrance: 36-39 CAG repeats (may or may not develop symptoms) 1
• Full penetrance: ≥40 CAG repeats (will develop disease if they live long enough) 1

Inheritance Patterns

When a woman has Huntington's disease:

• Each of her children (regardless of sex) has a 50% chance of inheriting the expanded HTT gene
• If the child inherits the expanded gene, they will develop HD if they live long enough (with full penetrance for ≥40 CAG repeats)

Gender Differences in Disease Transmission

While both men and women can inherit and transmit HD equally, there are some notable differences in transmission patterns:

• Juvenile-onset HD (symptoms before age 20) is more commonly inherited from fathers than mothers 2, 3

  • 12 out of 13 patients with onset before age 10 inherited HD from their father 3
  • This paternal transmission bias may be related to genomic imprinting 4

• CAG repeat instability during spermatogenesis can lead to larger expansions when transmitted from fathers 1

Clinical Implications for Women

Women with HD experience the same triad of symptoms as men:

• Motor dysfunction (typically chorea)
• Cognitive decline
• Psychiatric/emotional disturbances 2

Women considering pregnancy should be aware that:

• Prenatal testing is available for HD 1
• Genetic counseling is recommended before predictive testing 1
• Testing is typically not offered to individuals under 18 years old 1

Diagnostic Considerations

The diagnostic process is the same for both men and women:

• Genetic testing for CAG repeat expansion in the HTT gene is the definitive diagnostic test 2
• A positive family history may help with earlier diagnosis, though approximately 4.8% of HD patients have no known family history 5

In conclusion, Huntington's disease affects women and men equally as it is an autosomal dominant disorder. The HTT gene is located on chromosome 4, not on sex chromosomes, meaning women can both inherit and transmit the disease with the same 50% probability as men.