Myotonia in a 53-Year-Old Man and His Teenage Daughter

The earlier appearance of symptoms in the daughter is due to a phenomenon called:

1. Contraction
2. Anticipation
3. Variable Penetrance
4. Heteroplasmy
5. Co-dominance

The earlier onset and more severe symptoms in successive generations is called “anticipation.”

This is an interesting genetic phenomenon that was thought to be due to a bias resulting from more attention being given to the disease related symptoms in the younger generation.

It is clear now that this phenomenon is due to instability of a genetic mutation.

It is mostly noted in genetic disorders that are characterized by expansion of triplet repeats beyond a threshold.

Triple repeats exist in human genomes coding and non-coding components; most of the time, their expansion is harmless.

Examples of diseases caused by triplet repeat expansion:

1. Myotonic dystrohy type 1 (DM 1)
2. Hutingtons disease
3. Fragile X syndrome
4. Machedo Joseph disease
5. Freidrieck's ataxia

In Myotonic dystrophy, the expanded repeat is a CTG sequence in the non-coding region of protein kinase gene on chromosome 19.

A normal CTG repeat is between 5 and 37

38-49 repeats is called permutation, range and it increases the risk of having affected children.

A repeat of more than 50 is almost always symptomatic.

Interestingly, the number of CTG repeats positively correlates with an earlier onset and more severe disease.

The expanded repeats tend to expand further during meiosis, leading to a larger repeat in successive generations, which explains the phenomenon of anticipation.

The cause of instability of the CTG repeat is not clear.

More interestingly, CTG repeats expand when they go through a female germline and only rarely do so through a male germline. This explains the congenital form of the disease

Reference:
Athni S, Shaibani A, Ashizawa T. Anticipation and myotonic dystrophy: Diagnostic and prognostic implications. Resident and Staff Physician 42:57-63, 1996.