Chromosomal deletion syndrome

Overview

Chromosomal deletion syndrome refers to a group of genetic disorders caused by the loss (deletion) of a segment of a chromosome. This missing genetic material can affect many aspects of physical and cognitive development, depending on the size and location of the deletion. These syndromes can vary widely in severity, ranging from mild learning difficulties to significant congenital abnormalities. Common examples include 22q11.2 deletion syndrome (DiGeorge syndrome), 1p36 deletion syndrome, and Cri-du-chat syndrome (5p deletion).

Causes

Chromosomal deletion syndromes are caused by the loss of a section of DNA from a chromosome. The deletion can occur:

• Spontaneously (de novo): Most deletions happen by chance during the formation of reproductive cells or in early fetal development.

• Inherited: In rare cases, a parent may carry a balanced chromosomal rearrangement and pass an unbalanced deletion to the child.

• Chromosomal breakage or misrepair: Errors during cell division (especially meiosis) can result in deletions.

The impact of the deletion depends on how many and which genes are affected. Larger deletions typically cause more severe symptoms, but even small deletions can disrupt essential genes and lead to significant effects.

Symptoms

Symptoms of chromosomal deletion syndromes depend on the specific chromosome region affected and the genes involved. However, many deletion syndromes share common features, including:

• Developmental delays: Including delayed milestones in speech, motor skills, and learning

• Intellectual disability: Ranging from mild to severe

• Facial abnormalities: Such as a flat nasal bridge, low-set ears, or micrognathia

• Congenital anomalies: Including heart defects, cleft palate, or limb malformations

• Growth problems: Including failure to thrive or short stature

• Behavioral issues: Such as ADHD, autism spectrum disorder, or anxiety

• Seizures or other neurological symptoms

Each deletion syndrome may have a distinct clinical profile. For example:

• 22q11.2 deletion: Heart defects, immune deficiency, cleft palate, learning issues

• 5p deletion (Cri-du-chat): High-pitched cry, intellectual disability, microcephaly

• 1p36 deletion: Seizures, low muscle tone, distinctive facial features

Diagnosis

Diagnosis typically involves genetic testing and clinical evaluation. Steps include:

• Physical and developmental examination: Based on presenting symptoms and family history

• Karyotyping: Traditional chromosome analysis that can detect large deletions

• Chromosomal microarray (CMA): A high-resolution test that detects small deletions and duplications

• Fluorescence in situ hybridization (FISH): Used to confirm specific deletions, especially 22q11.2

• Whole exome or genome sequencing: In complex or undiagnosed cases

Parental testing may also be recommended to determine whether the deletion was inherited or de novo.

Treatment

There is no cure for chromosomal deletion syndromes, but treatment is focused on managing individual symptoms and maximizing developmental potential. A multidisciplinary approach is often necessary, including:

• Early intervention programs: For speech, occupational, and physical therapy

• Educational support: Special education plans tailored to the child’s needs

• Medical management: For congenital anomalies, heart defects, seizures, or feeding issues

• Behavioral therapy and psychological support: To address behavioral challenges and emotional health

• Genetic counseling: For families to understand recurrence risk and family planning options

Prognosis

The prognosis for chromosomal deletion syndromes depends on the specific deletion and severity of associated symptoms. Some children may lead relatively independent lives with mild impairments, while others may require lifelong medical and developmental support. Early diagnosis, access to therapies, and coordinated medical care can significantly improve developmental outcomes and quality of life. Continued research and advancements in genetic testing are improving diagnosis and guiding personalized treatment approaches.