Jacobsen syndrome

Overview

Jacobsen syndrome, also known as 11q deletion disorder, is a rare congenital condition caused by the deletion of genetic material from the long arm (q arm) of chromosome 11. The syndrome affects multiple organ systems and leads to a wide spectrum of physical, developmental, and behavioral abnormalities. Common features include distinctive facial characteristics, bleeding disorders, heart defects, intellectual disability, and delayed development. The condition is named after Danish physician Petrea Jacobsen, who first described it in 1973.

Causes

Jacobsen syndrome is caused by a partial deletion of the distal part of chromosome 11 at region q, most often between 11q23.3 and 11q25. The size and location of the deletion vary among individuals, influencing the severity of symptoms. Most cases are not inherited but occur as random events during the formation of reproductive cells or in early embryonic development. However, in rare instances, a parent may carry a balanced chromosomal rearrangement that predisposes to the deletion in offspring.

Symptoms

The clinical presentation of Jacobsen syndrome can vary widely but often includes:

• Distinctive facial features such as a broad nasal bridge, thin upper lip, widely spaced eyes, and downturned corners of the mouth

• Intellectual disability and developmental delay

• Speech and motor skill delays

• Congenital heart defects (e.g., ventricular septal defect, hypoplastic left heart)

• Bleeding disorders, most commonly Paris-Trousseau syndrome, due to abnormal platelet function

• Feeding difficulties in infancy

• Short stature

• Structural abnormalities in the brain or kidneys (in some cases)

• Behavioral issues such as attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), or obsessive-compulsive traits

Diagnosis

Diagnosis of Jacobsen syndrome typically begins with a clinical evaluation based on characteristic physical findings and developmental history. Confirmation is achieved through genetic testing, most commonly via:

• Karyotyping – to detect large chromosomal deletions

• Fluorescence in situ hybridization (FISH) – to identify smaller deletions in the 11q region

• Chromosomal microarray analysis (CMA) – a more sensitive method to detect and map deletions

Early diagnosis allows for prompt intervention and monitoring of potential complications.

Treatment

There is no cure for Jacobsen syndrome; treatment is symptomatic and supportive, tailored to the individual's needs. A multidisciplinary approach is often required and may include:

• Cardiac surgery or management for congenital heart defects

• Hematological support and monitoring for bleeding disorders

• Speech therapy, occupational therapy, and physical therapy for developmental delays

• Behavioral therapy and special education services for cognitive and emotional support

• Regular monitoring for complications such as infections, seizures, or growth issues

Prognosis

The prognosis for individuals with Jacobsen syndrome varies depending on the severity and combination of symptoms. Some children may have significant medical and developmental challenges, while others may experience milder symptoms. With appropriate medical care, therapy, and educational support, many individuals achieve developmental progress and improved quality of life. However, serious congenital defects, particularly heart anomalies and bleeding risks, can impact long-term outcomes and may require lifelong medical follow-up.