Jacobsen syndrome is a rare genetic disorder characterized by the loss of genetic material from a specific chromosome. Also known as 11q terminal deletion disorder, it involves a missing segment at the end of the long arm of chromosome 11. It affects approximately one in 100,000 newborns. Individuals with Jacobsen syndrome often experience a range of physical and developmental challenges, including distinctive facial features, developmental delays, cognitive impairment, congenital heart defects, and a bleeding disorder called Paris-Trousseau syndrome.
The Chromosomal Change
Jacobsen syndrome results from a specific genetic alteration involving chromosome 11. This alteration is a deletion, meaning a piece of genetic material is missing. The deletion occurs on the long arm, also known as the “q” arm, of chromosome 11.
The missing segment is typically located at the end of this long arm, specifically within the region known as 11q23.3, and often extends to the very end of the chromosome. The size of this deleted segment can vary among individuals, generally ranging from 7 to 16 million DNA base pairs. The severity of the symptoms often depends on the amount of genetic material that is missing; larger deletions typically lead to more pronounced health challenges.
This deleted region contains numerous genes important for normal growth and development across various body systems. When these genes are absent, it disrupts the body’s ability to develop and function properly. The loss of specific genes within this area contributes to the characteristic features of Jacobsen syndrome.
How the Change Occurs
The genetic change leading to Jacobsen syndrome most commonly arises spontaneously, meaning it is not inherited from a parent. This is referred to as a “de novo” deletion, accounting for about 85% to 92% of all cases. In these instances, the deletion occurs as a random error during the formation of reproductive cells, such as the egg or sperm, or very early in the development of the fetus. The parents of an individual with a de novo deletion typically have normal chromosomes and do not carry the specific genetic change.
Less frequently, the deletion can be inherited from a parent. This occurs in about 8% to 15% of cases and involves a parent who carries a chromosomal rearrangement known as a “balanced translocation.” A balanced translocation means that segments of two different chromosomes have exchanged places, but no genetic material is lost or gained. Because all the necessary genetic material is present, a parent with a balanced translocation is usually healthy and does not exhibit symptoms of Jacobsen syndrome.
However, when a parent with a balanced translocation produces reproductive cells, there is a possibility that the child will inherit an “unbalanced” form of this rearrangement. This unbalanced inheritance can result in the child having a missing segment of chromosome 11, leading to Jacobsen syndrome. In some cases, the child might also inherit extra genetic material from the other chromosome involved in the parent’s translocation.
Implications for Families
Genetic counseling is recommended for families with a child diagnosed with Jacobsen syndrome. A genetic counselor can help explain the specific chromosomal change, its potential effects, and the likelihood of it occurring in future pregnancies.
If the Jacobsen syndrome deletion is determined to be de novo, the risk of it happening again in a subsequent child for the same parents is generally considered very low, though not entirely absent due to the rare possibility of parental mosaicism. However, if the deletion was inherited from a parent with a balanced translocation, the recurrence risk for future children is significantly higher. In such cases, the genetic counselor can provide specific risk figures and discuss options for family planning.
Genetic testing for the parents after a child’s diagnosis determines the deletion’s origin. This testing helps clarify whether the deletion was a new event or inherited from a parental balanced translocation. This information is necessary for accurate risk assessment and reproductive planning.