Jacobsen syndrome

Jacobsen syndrome is a condition caused by a loss of genetic material from chromosome 11. Because this deletion occurs at the end (terminus) of the long (q) arm of chromosome 11, Jacobsen syndrome is also known as 11q terminal deletion disorder.

What is Jacobsen syndrome?

The signs and symptoms of Jacobsen syndrome vary considerably. Most affected individuals have delayed development, including the development of motor skills (such as sitting, standing, and walking) and speech. Most also have cognitive impairment and learning difficulties. Behavioral problems have been reported, including compulsive behavior (such as shredding paper), a short attention span, and easy distractibility. Many people with Jacobsen syndrome have been diagnosed with attention deficit-hyperactivity disorder (ADHD).

Jacobsen syndrome is also characterized by distinctive facial features. These include small and low-set ears, widely set eyes (hypertelorism) with droopy eyelids (ptosis), skin folds covering the inner corner of the eyes (epicanthal folds), a broad nasal bridge, downturned corners of the mouth, a thin upper lip, and a small lower jaw. Affected individuals often have a large head size (macrocephaly) and a skull abnormality called trigonocephaly, which gives the forehead a pointed appearance.

More than 90 percent of people with Jacobsen syndrome have a bleeding disorder called Paris-Trousseau syndrome. This condition causes a lifelong risk of abnormal bleeding and easy bruising. Paris-Trousseau syndrome is a disorder of platelets, which are blood cell fragments that are necessary for blood clotting.

Other features of Jacobsen syndrome can include heart defects, feeding difficulties in infancy, short stature, frequent ear and sinus infections, and skeletal abnormalities. The disorder can also affect the digestive system, kidneys, and genitalia. The life expectancy of people with Jacobsen syndrome is unknown, although affected individuals have lived into adulthood.

How common is Jacobsen syndrome?

The estimated incidence of Jacobsen syndrome is 1 in 100,000 newborns. More than 200 affected individuals have been reported.

What are the genetic changes related to Jacobsen syndrome?

Jacobsen syndrome is caused by a deletion of genetic material at the end of the long (q) arm of chromosome 11. The size of the deletion varies among affected individuals, with most affected people missing from about 5 million to 16 million DNA building blocks (also written as 5 Mb to 16 Mb). In almost all affected people, the deletion includes the tip of chromosome 11. Larger deletions tend to cause more severe signs and symptoms than smaller deletions.

The features of Jacobsen syndrome are likely related to the loss of multiple genes on chromosome 11. Depending on its size, the deleted region can contain from about 170 to more than 340 genes. Many of these genes have not been well characterized. However, genes in this region appear to be critical for the normal development of many parts of the body, including the brain, facial features, and heart. Researchers are working to determine which genes contribute to the specific features of Jacobsen syndrome.

Read more about chromosome 11.

Can Jacobsen syndrome be inherited?

Most cases of Jacobsen syndrome are not inherited. They result from a chromosomal deletion that occurs as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. Affected people typically have no history of the disorder in their family, though they can pass the chromosome deletion to their children.

Between 5 percent and 10 percent of people with Jacobsen syndrome inherit the chromosome abnormality from an unaffected parent. In these cases, the parent carries a chromosomal rearrangement called a balanced translocation, in which a segment from chromosome 11 has traded places with a segment from another chromosome. In a balanced translocation, no genetic material is gained or lost. Balanced translocations usually do not cause any health problems; however, they can become unbalanced as they are passed to the next generation.

Children who inherit an unbalanced translocation can have a chromosomal rearrangement with some missing genetic material and some extra genetic material. Individuals with Jacobsen syndrome who inherit an unbalanced translocation are missing genetic material from the end of the long arm of chromosome 11 and have extra genetic material from another chromosome. These chromosomal changes result in the health problems characteristic of this disorder.

What other names do people use for Jacobsen syndrome?

• 11q23 deletion disorder
• 11q deletion disorder
• 11q deletion syndrome
• 11q- deletion syndrome
• Jacobsen thrombocytopenia
• 11q terminal deletion disorder

External Links

Where can I find information about treatment for Jacobsen syndrome?

You might find information on treatment of Jacobsen syndrome in Educational resources and Patient support.

Where can I find additional information about Jacobsen syndrome?

You may find the following resources about Jacobsen syndrome helpful. These materials are written for the general public.

• MedlinePlus - Health information (2 links)
• Educational resources - Information pages (5 links)
• Patient support - For patients and families (6 links)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

• Gene Tests - DNA tests ordered by healthcare professionals
• PubMed - Recent literature
• OMIM - Genetic disorder catalog

See How are genetic conditions and genes named? in the Handbook.

What if I still have specific questions about Jacobsen syndrome?

• See How can I find a genetics professional in my area? in the Handbook.
• Ask the Genetic and Rare Diseases Information Center.
• Submit your question to Ask the Geneticist.

Where can I find general information about genetic conditions?

The Handbook provides basic information about genetics in clear language.

• What does it mean if a disorder seems to run in my family?
• What is a chromosome?
• Can changes in the number of chromosomes affect health and development?
• Are chromosomal disorders inherited?

These links provide additional genetics resources that may be useful.

• Genetics and health
• Resources for Patients and Families
• Resources for Health Professionals

What glossary definitions help with understanding Jacobsen syndrome?

ADHD; blood clotting ; cell; chromosome; clotting ; deletion; digestive; digestive system ; DNA ; egg ; epicanthal fold ; gene ; genitalia ; hyperactivity ; hypertelorism ; incidence ; infection ; kidney; macrocephaly ; Mb ; motor ; motor skill ; platelets; ptosis ; rearrangement ; reproductive cells ; short stature ; sign ; sinus ; sperm ; stature ; symptom ; syndrome ; thrombocytopenia; translocation

References

• Coldren CD, Lai Z, Shragg P, Rossi E, Glidewell SC, Zuffardi O, Mattina T, Ivy DD, Curfs LM, Mattson SN, Riley EP, Treier M, Grossfeld PD. Chromosomal microarray mapping suggests a role for BSX and Neurogranin in neurocognitive and behavioral defects in the 11q terminal deletion disorder (Jacobsen syndrome). Neurogenetics. 2009 Apr;10(2):89-95. Epub 2008 Oct 15. PubMed citation
• Grossfeld PD, Mattina T, Lai Z, Favier R, Jones KL, Cotter F, Jones C. The 11q terminal deletion disorder: a prospective study of 110 cases. Am J Med Genet A. 2004 Aug 15;129A(1):51-61. PubMed citation
• Mattina T, Perrotta CS, Grossfeld P. Jacobsen syndrome. Orphanet J Rare Dis. 2009 Mar 7;4:9. Review. PubMed citation
• Penny LA, Dell'Aquila M, Jones MC, Bergoffen J, Cunniff C, Fryns JP, Grace E, Graham JM Jr, Kousseff B, Mattina T, et al. Clinical and molecular characterization of patients with distal 11q deletions. Am J Hum Genet. 1995 Mar;56(3):676-83. PubMed citation
• Tyson C, Qiao Y, Harvard C, Liu X, Bernier FP, McGillivray B, Farrell SA, Arbour L, Chudley AE, Clarke L, Gibson W, Dyack S, McLeod R, Costa T, Vanallen MI, Yong SL, Graham GE, Macleod P, Patel MS, Hurlburt J, Holden JJ, Lewis SM, Rajcan-Separovic E. Submicroscopic deletions of 11q24-25 in individuals without Jacobsen syndrome: re-examination of the critical region by high-resolution array-CGH. Mol Cytogenet. 2008 Nov 11;1:23. PubMed citation
• Unique: Chromosome 11q Deletion Disorder: Jacobsen Syndrome