22q11.2 duplication syndrome results from an extra copy of a small segment of chromosome 22 at location q11.2. The characteristics of this syndrome vary widely, even within the same family. Some people with the duplication experience developmental delays, intellectual disabilities, slow growth, and low muscle tone. Conversely, many individuals show no obvious physical or intellectual differences and may go undetected.
Due to this wide range of expression, many people with the duplication are likely undiagnosed. Most diagnoses occur when individuals are tested for other reasons, as its features are often nonspecific and require genetic testing to identify.
Genetic Basis of the Syndrome
Human cells contain chromosomes that hold our genetic information. This condition involves an extra piece of genetic material on the long, or “q” arm, of chromosome 22 at position 11.2. Most commonly, the duplicated segment is about 3 million DNA building blocks (3 megabases) in size and contains 30 to 40 genes.
The duplication can happen in two primary ways. In many instances, it is inherited from a parent in an autosomal dominant pattern, giving a child a 50% chance of inheritance from an affected parent. Often, the parent may have a mild presentation and be unaware they carry the duplication. In other cases, the duplication is not inherited but occurs as a new, or de novo, event. This random genetic change happens during the formation of reproductive cells or early in fetal development. Individuals with a de novo duplication are the first in their family to have the condition but can pass it to their children.
Associated Physical and Developmental Features
One of the most frequently reported characteristics is some degree of developmental delay, which can manifest as delayed speech and language skills or challenges with motor skills. Weak muscle tone, or hypotonia, is a common finding that can contribute to these motor delays.
Cognitive and learning differences are also associated with the syndrome. The spectrum of intellectual ability is broad, ranging from severe intellectual disability to mild learning difficulties, while many individuals have no cognitive impairments. Due to this variability, it is difficult to predict the level of intellectual impact based solely on the duplication’s presence.
A number of physical health conditions can be associated with this duplication. Some individuals may be born with congenital heart defects, while others might have abnormalities of the kidneys or urinary tract. Differences in the structure of the palate, such as a high-arched palate, may also occur and can affect speech.
Behavioral and psychiatric differences are also noted in some individuals with the duplication. There can be an increased likelihood of being diagnosed with conditions such as autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), anxiety, and other mood disorders.
The Diagnostic Process
The diagnosis of 22q11.2 duplication syndrome is confirmed through specialized genetic testing, as it cannot be identified by physical features alone. The most common diagnostic tool is a chromosomal microarray (CMA). This test is highly sensitive and can detect small genetic changes like the duplication on chromosome 22.
Older genetic testing methods, like a standard karyotype analysis, are generally not able to detect such a small duplication. Another test, Fluorescence In Situ Hybridization (FISH), can be used to look for this specific duplication. A FISH test is often utilized when there is a known family history of the condition.
Genetic testing might be recommended under several circumstances. Prenatally, if an ultrasound reveals findings like congenital heart defects or urogenital anomalies, further testing may be suggested. Postnatally, a child who presents with developmental delays, hypotonia, and slow growth might be referred for genetic testing to determine an underlying cause.
Management and Support Strategies
Managing 22q11.2 duplication syndrome involves a multidisciplinary team of specialists to address the specific needs of the individual. Because the condition can affect various parts of the body, experts like a cardiologist or a nephrologist may be involved. Regular developmental assessments with a developmental pediatrician are also common to track progress and identify needs early.
Therapeutic interventions are a primary support for developmental delays. Speech therapy can help with language acquisition and issues related to palatal differences. Occupational therapy focuses on improving fine motor skills and daily living activities, while physical therapy can help with gross motor skills and muscle tone.
Educational support is another important aspect of management for school-aged children. Some students may benefit from an Individualized Education Program (IEP) or other services to address learning disabilities. Behavioral and mental health services can also provide support for individuals and their families in managing conditions like ADHD or anxiety.