Williams syndrome is a rare genetic condition that affects various parts of the body, presenting with a unique combination of medical and developmental characteristics. This disorder arises from a specific alteration in an individual’s genetic material. Understanding this genetic change is central to comprehending the diverse features observed in those with the syndrome.
Understanding Karyotypes
A karyotype provides an organized display of a person’s chromosomes, which are thread-like structures found within the nucleus of cells. Each chromosome contains tightly packed DNA, carrying genetic instructions. Scientists arrange these chromosomes in pairs, ordered by size from largest to smallest, and also categorize them by the position of a constricted region called the centromere. This visual map helps identify any numerical or structural abnormalities in an individual’s complete set of chromosomes.
The Genetic Signature of Williams Syndrome
Williams syndrome is specifically caused by a microdeletion on chromosome 7. This microdeletion occurs in the 7q11.23 region, a particular segment on the long arm of chromosome 7. This genetic change involves the spontaneous deletion of approximately 25 to 28 genes from this specific region. Among the genes affected by this deletion is the ELN gene, which provides instructions for making the protein elastin.
This deletion in the 7q11.23 region is considered a “contiguous gene syndrome” because all the deleted genes are located next to each other in this critical region. The absence of these genes, particularly ELN, leads to haploinsufficiency, meaning there is only one functional copy of these genes instead of the usual two. This reduced gene dosage underlies the various features of Williams syndrome. While typically a random event during egg or sperm formation, in rare cases, it can be inherited in an autosomal dominant manner.
Identifying the Genetic Change
The specific microdeletion associated with Williams syndrome is primarily detected through specialized laboratory methods. Fluorescence In Situ Hybridization (FISH) is a common technique used for this purpose. This test uses fluorescently labeled DNA probes designed to bind to the specific region on chromosome 7 that is typically deleted in Williams syndrome. If the deletion is present, the probe will not bind, or bind weakly, indicating the absence of that genetic material.
Chromosomal microarray (CMA) is another advanced diagnostic method that can identify this microdeletion. CMA offers a more comprehensive analysis, scanning the entire genome for smaller deletions or duplications that FISH might not detect. Both FISH and CMA analyze a patient’s DNA to confirm the presence of the characteristic 7q11.23 microdeletion, providing a definitive diagnosis.
How the Genetic Change Shapes Characteristics
The deletion of genes on chromosome 7, particularly the ELN gene, directly contributes to the varied characteristics observed in individuals with Williams syndrome. The absence of one copy of the ELN gene leads to insufficient production of elastin, a protein that provides elasticity to blood vessels and other connective tissues. This deficiency often results in cardiovascular problems, such as narrowing of major blood vessels like the aorta or pulmonary artery. Elastin insufficiency also contributes to distinctive facial features, such as a broad forehead and full cheeks, and can affect the voice, making it hoarse.
Beyond ELN, the deletion of other genes in the 7q11.23 region influences cognitive and behavioral traits. For instance, haploinsufficiency of genes like LIMK1, GTF2I, and GTF2IRD1 is thought to contribute to characteristic challenges with visuospatial tasks, despite often strong verbal abilities. Other genes in the deleted region, including CLIP2, are linked to the unique behavioral characteristics, such as an overly friendly and sociable personality. These genetic losses collectively impact development, shaping the specific physical attributes, cognitive profiles, and social behaviors seen in individuals with Williams syndrome.