Familial FTD

Frontotemporal dementia (FTD) can be separated into familial FTD and sporadic FTD. Familial FTD occurs when multiple people in a family across back-to-back generations have FTD or a related condition. The multiple people are usually closely related to each other, like a grandparent, parent and adult child, and they all belong to one side of the family or the other, not both. Sporadic FTD occurs when only one person in a family has FTD.

Some familial FTD has no known cause. Some familial FTD happens because of a single gene cause. This is known as genetic FTD. About 10–20% of all cases of FTD is considered genetic FTD. Genetic FTD is due to a single gene change or variant, known as an illness-causing gene mutation. The majority of genetic FTD is caused by an illness-causing mutation in one of three genes: C9ORF72, MAPT or GRN. Rarely, it is caused by an illness-causing mutation in one of other genes: TARDBP, VCP, CHMP2B, SQSTM1, UBQLN1 or TBK1.

Genetic FTD is passed down in families in a dominant pattern. This means that the child of a person with a FTD-causing gene mutation has a 50 percent, or 1 in 2, chance to have the same mutation. With some exceptions, nearly every person with a FTD-causing gene mutation will develop FTD or a related condition if he lives until the eighth decade. The usual age of the first symptom varies, depending on which FTD-causing gene mutation is present. It is not uncommon for first symptoms to occur during ages 50–60. However, the age range of the first symptom spans from ages 30–40 to the seventh decade of life.

Genes Associated with Genetic FTD

C9ORF72 gene (also known as the FTD-ALS or C9 gene)

  • C9 mutations cause FTD, amyotrophic lateral sclerosis (ALS) or a combination of both conditions in a person.
  • Whether a person will develop FTD or ALS or a combination cannot be predicted for healthy people at risk.
  • C9 mutations are the most common cause of genetic FTD. They are also the most common cause of genetic ALS.

MAPT gene (called the “map-T” gene).

  • MAPT mutations usually cause FTD (behavioral type).
  • Sometimes MAPT mutations cause conditions associated with progressive supranuclear palsy or corticobasal degeneration pathology. People with these pathologies often have a type of movement disorder.
  • Certain MAPT mutations cause an Alzheimer’s-like symptoms.
  • Families with a MAPT mutation nearly always have a strong family history of FTD (behavioral type), with multiple symptomatic people across back-to-back generations.
  • MAPT mutations do not cause ALS.

GRN gene (also known as the progranulin gene)

  • GRN mutations usually cause FTD (behavioral type).
  • GRN mutations can cause a progressive language and/or speech disorder, known as primary progressive aphasia (PPA).
  • GRN mutations can cause a movement disorder, including parkinsonism or corticobasal syndrome.
  • GRN mutations can cause Alzheimer’s-like symptoms.
  • Families with a GRN mutation usually have a strong family history of FTD (behavioral type) and/or PPA with or without parkinsonism.
  • Rarely, GRN mutations cause ALS.

Rare Genes Associated with Genetic FTD

TARDBP gene

  • TARDBP mutations cause FTD, ALS or a combination of both conditions in a person.

VCP gene

  • VCP mutations cause inclusion body myopathy, an adult-onset neurologic condition characterized by progressive muscle weakness. It diminishes a person’s ability to walk, swallow and breathe. Many people with a VCP mutation and inclusion body myopathy also have Paget’s disease of bone.
  • Some people with a VCP mutation also have FTD (behavioral type).

CHMP2B gene

  • In one large Danish family, a CHMP2B mutation causes FTD (behavioral type).

SQSTM1 gene

  • SQSTM1 mutations cause FTD, ALS or a combination of both conditions in a person.
  • People with a SQSTM1 mutation can have Paget’s disease of bone.

UBQLN1 gene

  • UBQLN1 mutations cause FTD, ALS, or a combination of both conditions in a person.
  • Families with a UBQLN1 mutation usually have more men than women with symptoms. However, women can also develop symptoms. Both men and women are at risk. Men with a UBQLN1 mutation can never pass it on to sons.

TBK1 gene

  • TBK1 mutations can cause FTD, ALS or a combination of both conditions in a person.

Genetic Counseling

For a genetic risk assessment of your own family history, contact a genetic counselor or other genetic professional with expertise in neurodegenerative disease.