Jacobsen Syndrome: A Complete Chromosome Deletion Disorder

疾患概要

Overview of Jacobsen Syndrome

Discovery and Prevalence

First described by Jacobsen in 1973, this syndrome is linked to deletions in the chromosomal region 11q23.3–q25. It occurs in approximately 1 in 50,000 to 100,000 live births, with about 70 percent of cases affecting females. Roughly 85 percent of cases result from spontaneous (de novo) mutations, while the remainder are inherited.

Clinical Variability

The symptoms and severity vary based on the size and location of the deletion. Common hallmarks include prenatal and postnatal growth delays, motor and intellectual developmental delays, and distinctive facial features such as a wide nasal bridge, downturned mouth, and small chin.

A defining feature of Jacobsen Syndrome is Paris-Toussaint bleeding disorder, present in nearly 88.5 percent of cases. This condition, caused by a low platelet count from birth, often leads to increased bleeding risk and, in some cases, immune deficiencies.

Other complications often include congenital heart defects, kidney and urinary tract abnormalities, gastrointestinal and skeletal issues, and sensory problems involving vision or hearing. Neurological involvement and hormonal imbalances are also documented.

Genetic Cause and Diagnosis

Chromosomal Mechanism

Jacobsen Syndrome results from deletions on the long arm of chromosome 11, affecting regions tied to the cohesin complex responsible for chromosome alignment during cell division. Most cases involve terminal deletions that span between 7 and 16 megabases. Smaller or intermediate deletions may result in a milder presentation, often referred to as partial Jacobsen Syndrome.

Occasionally, the breakpoint occurs at a fragile site (FRA11B), leading to a mosaic pattern in which some cells carry the deletion while others do not, moderating symptom severity.

Diagnostic Approaches

Diagnosis begins with recognition of characteristic clinical signs and is confirmed through genetic testing.

• Array Comparative Genomic Hybridization (array CGH) detects the size and location of chromosomal deletions.
  
• Fluorescence In Situ Hybridization (FISH) is often used for confirmation.
  
• Prenatal testing can be performed using DNA from amniotic fluid or chorionic villi.
  
• Non-invasive prenatal testing (NIPT), analyzing fetal DNA in maternal blood, may identify deletions, though its accuracy for Jacobsen Syndrome is not yet fully validated.
  

In about 90 percent of cases, the deletion is de novo. Inherited cases typically stem from a parent with a balanced chromosomal translocation or, more rarely, a parent carrying a terminal 11q deletion.

Symptoms and Management

Craniofacial Features

Individuals often display a combination of distinct craniofacial traits, including:

• Unusual head shape and widely spaced eyes
  
• Ptosis (drooping eyelids) or coloboma (eye tissue defect)
  
• Downward-slanting eye openings and epicanthal folds
  
• Broad nasal bridge, short nose, V-shaped mouth, and small chin
  
• Low-set, backward-rotated ears
  

Premature fusion of cranial sutures, known as craniosynostosis, can also occur and may require surgical correction in infancy.

Heart and Hematological Complications

Bleeding issues are among the most critical health concerns. Approximately 88.5 percent of patients have thrombocytopenia, leading to easy bruising, prolonged bleeding, and elevated risk of internal bleeding.

Congenital heart defects are frequent and often include ventricular septal defects, atrial septal defects, or patent ductus arteriosus. These defects often require surgical intervention early in life.

Growth and Developmental Challenges

Growth delays are typical, often resulting in short stature linked to growth hormone deficiencies. Although growth hormone therapy can be considered, it must be approached cautiously because of a possible increased tumor risk in these patients.

Immune and Sensory Issues

Immune deficiencies, particularly lymphopenia, leave many individuals more vulnerable to infections. Visual and hearing impairments are common, including strabismus, cataracts, or other structural eye issues.

Neurological and Behavioral Concerns

Most individuals present with intellectual disabilities of varying severity. Some also display traits of ADHD, autism spectrum disorders, or emotional and behavioral difficulties.

Treatment and Multidisciplinary Support

Symptom-Focused Care

There is no cure for Jacobsen Syndrome. Treatment centers on managing symptoms and preventing complications through a coordinated care approach.

Key strategies include:

• Surgical interventions for craniofacial defects, craniosynostosis, or congenital heart conditions
  
• Physical, occupational, and speech therapies, along with behavioral support programs
  
• Ongoing monitoring of heart, kidney, and endocrine functions
  
• Preventive measures for immune deficiencies, including immunization and infection management
  
• Hormonal therapy for thyroid or other endocrine deficiencies
  

Genetic counseling to guide family planning and provide support

Prognosis

Survival and Quality of Life

The prognosis is highly variable. Severe heart defects, bleeding complications, and immune deficiencies can significantly affect survival, particularly in infancy. Early interventions such as platelet transfusions, antibiotics, and corrective heart surgery can improve outcomes.

Many children who survive the neonatal period reach adulthood, though they often require lifelong medical and developmental support. Intellectual abilities range from mild learning delays to severe cognitive impairment.

The longest documented survival is at least 45 years, showing that with consistent and comprehensive care, long-term survival is possible.

Conclusion

Jacobsen Syndrome is a complex, rare genetic disorder with a broad clinical spectrum. Early diagnosis, careful monitoring, and integrated multidisciplinary care significantly improve outcomes and quality of life. Support for families, combined with ongoing advances in genetic medicine, continues to shape better approaches to managing this condition.

References

Mattina, T., Perrotta, C. S., & Grossfeld, P. (2009). Jacobsen syndrome. Orphanet Journal of Rare Diseases, 4(1), 9.
Jatczak-Gaca, A. (2023). Hematological aberrations in patient with Jacobsen syndrome. Acta Haematologica Polonica, VM/OJS/J/96831.
Perez, G., Barber, G. P., Benet-Pages, A., Casper, J., Clawson, H., Diekhans, M., Fischer, C., Gonzalez, J. N., Hinrichs, A. S., Lee, C. M., Nassar, L. R., Raney, B. J., Speir, M. L., van Baren, M. J., Vaske, C. J., Haussler, D., Kent, W. J., & Haeussler, M. (2024). The UCSC Genome Browser database: 2025 update. Nucleic Acids Research, gkae974.