What Is Familial Down Syndrome and How Is It Inherited?

Down syndrome is a genetic condition caused by an extra full or partial copy of chromosome 21, which alters development. While most instances of Down syndrome result from a random event during cell division, a small fraction of cases are inherited. This inherited form, known as familial Down syndrome, originates from a specific type of chromosomal rearrangement in a parent that can be passed down through generations.

The Genetic Mechanism of Familial Down Syndrome

The most common cause of Down syndrome is Trisomy 21, accounting for about 95% of cases. It results from a random error in cell division called nondisjunction, where a pair of 21st chromosomes fails to separate during egg or sperm formation. This event is not hereditary, and the risk increases with maternal age.

Familial Down syndrome stems from a translocation, a structural rearrangement where a piece of one chromosome attaches to another. This is often a Robertsonian translocation, where part of chromosome 21 attaches to another chromosome, like number 14. Translocation is responsible for about 2-3% of all cases.

A person can carry this rearranged chromosome without any health effects, which is known as a balanced translocation. Although carriers are unaffected by the rearrangement, they can pass it to their children.

Inheritance Patterns and Carrier Status

A person with a rearranged chromosome 21 but the correct amount of genetic material is a “balanced translocation carrier.” These individuals are healthy and show no signs of Down syndrome, often unaware they are carriers until they have an affected child.

A carrier can produce reproductive cells with an incorrect amount of genetic material. During the formation of eggs or sperm, this can lead to a child inheriting normal chromosomes, becoming a carrier, or inheriting an “unbalanced” set. An unbalanced inheritance provides extra chromosome 21 material, leading to Down syndrome.

The risk of a carrier having a child with Down syndrome depends on which parent has the translocation. If the mother is the carrier, the risk is about 10-15%. If the father is the carrier, the risk is lower, around 3-5%.

Genetic Testing and Counseling

For families concerned about familial Down syndrome, genetic testing provides clear answers. A blood test called a karyotype analysis examines a parent’s chromosomes. This test creates a picture of the chromosomes, allowing doctors to see if a balanced translocation is present.

If a parent is a carrier, prenatal testing is available during pregnancy to check the fetus’s chromosomes. Procedures like chorionic villus sampling (CVS) or amniocentesis analyze fetal cells for an unbalanced translocation. CVS is done between 10 and 13 weeks of pregnancy, while amniocentesis is performed between 15 and 20 weeks.

Genetic counseling is an important part of this process. A genetic counselor helps families understand karyotype results and what it means to be a carrier. They provide information on inheritance risks and family planning options, supporting families in making informed decisions.

Comparing Types of Down Syndrome

From a clinical perspective, individuals with translocation Down syndrome are virtually indistinguishable from those with Trisomy 21. The physical and developmental patterns are the same because both conditions result from extra genetic material from chromosome 21.

The fundamental difference between the types lies in their origin and implications for future pregnancies. Trisomy 21 is a sporadic event, meaning the recurrence risk in a subsequent pregnancy is low, around 1% for mothers under 40. Translocation Down syndrome carries a higher, predictable recurrence risk depending on which parent is the carrier.

A third, rarer type is Mosaic Down syndrome, where the extra chromosome 21 is present in only some cells. This is also a random event that occurs after fertilization. Of the three types, only translocation Down syndrome has a hereditary component.