7q11.23 duplication syndrome
7q11.23 duplication syndrome is a genetic condition characterized by a variety of neurological and behavioral issues, developmental delays, and potential physical abnormalities.
Overview
People with 7q11.23 duplication syndrome typically experience delayed development of speech and motor skills, such as crawling and walking. These speech and motor challenges may persist throughout life. Affected individuals may also exhibit hypotonia (weak muscle tone) and abnormal movements, such as involuntary movements on one side of the body that mirror intentional movements on the other. Approximately one-fifth of affected individuals experience seizures.
Intellectual Development
Intellectual development varies significantly among those with the condition:
- The majority have low-average to average intelligence.
- About one-third of individuals have intellectual disability or borderline intellectual ability.
- Rarely, individuals may have above-average intelligence.
Neurodevelopmental and Behavioral Features
Associated neurodevelopmental problems include:
- Anxiety disorders, such as social phobias and selective mutism.
- Attention-deficit/hyperactivity disorder (ADHD).
- Physical aggression and excessively defiant behavior (oppositional disorder).
- Autism spectrum disorder affecting communication and social interaction.
Physical Characteristics
Approximately half of affected individuals have enlargement (dilatation) of the aorta, the blood vessel carrying blood from the heart to the rest of the body. This can worsen over time and lead to life-threatening complications if the aortic wall separates into layers or ruptures.
Distinctive facial features may include:
- A large head (macrocephaly) that is flattened in the back (brachycephaly).
- A broad forehead, straight eyebrows, and deep-set eyes with long eyelashes.
- A broad nose tip with a low-inserted columella, resulting in a shortened philtrum.
- A high arch in the roof of the mouth and ear abnormalities.
Causes
The syndrome results from an extra copy of a region on the long (q) arm of chromosome 7. This region, known as the Williams-Beuren syndrome critical region (WBSCR), is 1.5 to 1.8 million DNA base pairs in length and contains 26 to 28 genes. Extra copies of the ELN and GTF2I genes are believed to contribute to the condition's features, with ELN potentially linked to aortic dilatation and GTF2I associated with behavioral features.
Inheritance
This is an autosomal dominant condition, meaning one copy of the duplicated chromosome 7 is sufficient to cause the disorder. Most cases result from a duplication occurring during the formation of reproductive cells. In about one-quarter of cases, the duplication is inherited from a parent who may have subtle, undiagnosed signs of the condition.