Creutzfeldt-Jakob disease (CJD) can indeed run in families, but this occurs in a specific form known as familial or genetic CJD. This form is caused by inherited mutations in the *PRNP* gene, which encodes the prion protein. These mutations lead to abnormal folding of the prion protein, which then accumulates in the brain and causes neurodegeneration[1][4][6].
CJD is a prion disease, meaning it is caused by misfolded prion proteins (PrP^Sc) that induce normal prion proteins (PrP^C) to also misfold, leading to brain damage characterized by spongiform degeneration[1]. While most cases of CJD are sporadic (about 85%), meaning they occur without a known cause or family history, approximately 5–15% of cases are familial, resulting from inherited mutations in *PRNP*[6].
### Genetic Basis and Inheritance Pattern
Familial CJD is inherited in an **autosomal dominant** pattern. This means that a single copy of the mutated gene inherited from one parent is sufficient to cause the disease. Each child of an affected parent has a 50% chance of inheriting the mutation and potentially developing the disease[4]. The mutations in *PRNP* associated with familial CJD include several specific point mutations, such as the D178N mutation, among others[4].
The *PRNP* gene is located on chromosome 20 and encodes the major prion protein. Variations in this gene, including mutations and polymorphisms, influence susceptibility to prion diseases and their clinical manifestations[3]. For example, the polymorphism at codon 129 (methionine or valine) affects disease subtype and progression[1][3].
### Clinical and Pathological Features
Familial CJD shares many clinical features with sporadic CJD, including rapidly progressive dementia, motor dysfunction, and characteristic brain changes visible on MRI and confirmed by neuropathology. However, familial cases may have distinct clinical subtypes depending on the specific mutation and codon 129 genotype[1].
Other inherited prion diseases related to *PRNP* mutations include Gerstmann-Sträussler-Scheinker disease (GSS) and fatal familial insomnia (FFI). These diseases also follow an autosomal dominant inheritance pattern and are caused by different mutations in the same gene[2]. GSS, for example, is associated with the P102L mutation and shows almost complete penetrance, meaning nearly all individuals with the mutation develop the disease[2].
### Penetrance and Risk
Penetrance refers to the likelihood that a person carrying a disease-causing mutation will actually develop the disease. Familial prion diseases, including familial CJD, generally have high penetrance, though this can vary depending on the mutation. This means that most individuals who inherit the mutation will eventually show symptoms, although the age of onset and disease course can vary[2].
### Non-Familial Forms of CJD
It is important to distinguish familial CJD from other forms:
– **Sporadic CJD (sCJD):** The most common form, occurring without known genetic cause or exposure.
– **Acquired CJD:** Resulting from exposure to infectious prions, such as through contaminated medical instruments or consumption of prion-contaminated beef (variant CJD)[1][2].
Familial CJD is not contagious in the usual sense; it is inherited genetically rather than transmitted by casual contact[2].
### Summary of Key Points
| Aspect | Details |
|—————————–|——————————————————————————————-|
| Cause | Mutations in *PRNP* gene causing abnormal prion protein folding |
| Inheritance pattern | Autosomal dominant |
| Risk to offspring | 50% chance per pregnancy if one parent affected |
| Penetrance | High (most carriers develop disease) |
| Relation to other prion diseases | Related to GSS and FFI, also caused by *PRNP* mutations |
| Sporadic vs familial cases | Familial cases ~5–15% of all CJD; sporadic cases ~85% |
| Contagiousness | Familial CJD is not contagious; transmission requires direct exposure to infected tissue |
The genetic nature of familial CJD means that family members of affected individuals may consider genetic counseling and testing to understand their risk. However, because of the rarity and severity of the disease, such decisions are complex and should be guided by specialists.
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**Sources:**
[1] Radiopaedia, “Creutzfeldt-Jakob disease,” https://radiopaedia.org/articles/creutzfeldt-jakob-disease?lang=us
[2] National Organization for Rare Disorders, “Gerstmann-Sträussler-Sch
