Structural abnormalities: deletions (Cri du Chat) and duplications (Pallister Killian)

What are structural chromosome abnormalities?

Structural chromosome abnormalities occur when there is a change in the structure or components of a chromosome. The total number of chromosomes is usually normal (46 total per cell). Structural chromosome abnormalities occur when part of a chromosome is missing, a part of a chromosome is extra, or a part has switched places with another part. Ultimately, this leads to having too much or too little genetic material, which is a cause of some birth defects.

Each chromosome has many segments which are usually divided into a "short arm" and a "long arm" of the chromosome. The short arm which is the upper half of the chromosome, is known as the "p arm" and the long arm, which is the lower half of the chromosome, is the "q arm."

What are deletions?

The term "deletion" simply means that a part of a chromosome is missing or "deleted". A very small piece of a chromosome can contain many different genes. When genes are missing, there may be errors in the development of a baby, since some of the "instructions" are missing. One example of a genetic syndrome caused by a deletion is called "Cri du Chat", where part of the #5 chromosome is missing or deleted.

What is Cri du Chat?

Cri du Chat or "Cat Cry syndrome" is found in approximately 50 to 60 children each year born in the United States. Cri du Chat is caused by a deletion of chromosome 5p, which is written "5p-". Babies with Cri du Chat have a high pitched cry, poor muscle tone, a small head size and low birthweight. They also have problems with language, where they may express themselves by using a small number of words or sign language. Other health problems can be present including delays in walking, problems with feeding, hyperactivity, scoliosis, and severe intellectual disabilities. Most persons with Cri du Chat will have a normal life span, unless they are born with other serious organ defects.

Educational intervention at an early age, in addition to physical and language therapy, are important for children with Cri du Chat to reach their full potential.

What are duplications?

The term "duplication" simply means that a part of a chromosome is duplicated, or present in two copies. This results in having extra genetic material, even though the total number of chromosomes is usually normal. Since a very small piece of a chromosome can contain many different genes, the extra genes present in a duplication may cause those genes to not function properly. This can lead to errors in the development of a baby due to these "extra instructions". One way to think of a duplication is to think of all 46 chromosomes as a cookbook, and each individual chromosome as a recipe. If a deletion is a missing ingredient in the recipe, a duplication is an extra ingredient in a recipe. One example of a genetic syndrome caused by a duplication is called "Pallister Killian syndrome", where part of the #12 chromosome is duplicated.

This newly formed chromosome is called the translocation chromosome. The translocation in this example is between chromosomes #14 and 21. When a baby is born with this type of translocation chromosome (between #14 & 21), in addition to one normal #14 and two normal #21 chromosomes, the baby will have Down syndrome. This is also called translocation Down syndrome.

What is Pallister Killian syndrome?

Pallister Killian syndrome is a result of extra #12 chromosome material. There is usually a mixture of cells (mosaicism), some with extra #12 material, and some that are normal (46 chromosomes without the extra #12 material). Babies with this syndrome have many problems including severe intellectual disabilities, poor muscle tone, "coarse" facial features, and a prominent forehead. They tend to have a very thin upper lip with a thicker lower lip and a short nose. Other health problems include seizures, poor feeding, stiff joints, cataracts in adulthood, hearing loss, and heart defects. Persons with Pallister Killian do have a shortened life span, but can live into their 40's.