SNP Shot: Genomic Insights

WAGR syndrome is a complex condition affecting multiple body systems, characterized by a specific combination of features: Wilms tumor, aniridia, genitourinary abnormalities, and developmental delays.

A significant percentage, between 45% and 60%, of individuals with WAGR syndrome develop Wilms tumor, a rare kidney cancer. While primarily diagnosed in children, it can occasionally occur in adults. Some individuals with WAGR syndrome may also develop nephrogenic rests, which are abnormal cell clusters in the kidneys. These rests can increase the risk of Wilms tumor, although not all individuals with nephrogenic rests develop cancer.

Aniridia, the absence of the iris (the colored part of the eye), is present in most individuals with WAGR syndrome. This condition can lead to reduced visual acuity, increased sensitivity to light (photophobia), and is often the first noticeable indication of the syndrome. Additional eye problems, such as cataracts (clouding of the lens), glaucoma (increased eye pressure), and nystagmus (involuntary eye movements), may also arise.

Genitourinary anomalies are more common in males with WAGR syndrome compared to females. The most prevalent abnormality in males is cryptorchidism, or undescended testes. Affected females may have non-functional ovaries and underdeveloped tissue called streak gonads. A bicornate uterus (heart-shaped uterus) may also be present in females, potentially causing difficulties in carrying a pregnancy to full term.

Developmental delays and intellectual disability are frequently observed in individuals with WAGR syndrome. These individuals often experience challenges with information processing, learning, and responding appropriately. Many have difficulties with speech and language comprehension. Psychiatric or behavioral issues, such as depression, anxiety, attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), or autism spectrum disorder, can also be present.

Additional signs and symptoms of WAGR syndrome can include chronic constipation, pancreatitis (inflammation of the pancreas), kidney failure, respiratory problems, and allergies. Some affected children may develop obesity. When obesity is present from childhood, the condition is sometimes referred to as WAGRO syndrome.

Inheritance:

In most cases, WAGR syndrome is not inherited. It results from a spontaneous chromosomal deletion during the formation of egg or sperm cells, or early in fetal development. Typically, there is no family history of the disorder in affected individuals.

Rarely, WAGR syndrome is inherited. In these instances, a parent who does not exhibit symptoms of the condition carries a balanced translocation, a chromosomal rearrangement where a segment of chromosome 11 is moved to another chromosome without any gain or loss of genetic material.

However, the translocation can become unbalanced during the passage of genetic information to the next generation. A child may inherit a chromosome 11 lacking a portion of its short arm, leading to WAGR syndrome.