1p36 deletion syndrome is a rare genetic condition that arises from a missing piece of genetic material. This syndrome is considered one of the most common chromosome deletion disorders, affecting approximately 1 in 5,000 to 1 in 10,000 live births. The syndrome presents with a range of features, including developmental delays and distinct physical characteristics.
The Chromosomal Abnormality
Within every human cell, genetic information is organized into structures called chromosomes. These thread-like structures contain deoxyribonucleic acid (DNA), which carries the instructions for the body’s development and function. Humans typically have 23 pairs of chromosomes, with one copy of each pair inherited from each parent, totaling 46 chromosomes.
1p36 deletion syndrome occurs when a segment of genetic material is missing from a specific location on chromosome 1. This missing piece is found on the short arm, designated “p,” at band 36. The “p” arm is the shorter segment of the chromosome located above the centromere, the constricted region joining the two arms. The name “1p36 deletion” precisely indicates the chromosome, its short arm, and the specific band where the genetic loss occurs.
The size of this deleted segment can vary among affected individuals, ranging from approximately 1.5 million to over 10 million base pairs. The signs and symptoms associated with 1p36 deletion syndrome are thought to result from the loss of multiple genes located within this specific region. These genes are important for the proper development of various bodily systems, including the brain, heart, and skeleton, contributing to the diverse clinical presentation of the syndrome.
The breakpoints for these deletions are variable, commonly found between 1p36.13 and 1p36.33. Even small deletions can lead to many features associated with the syndrome, indicating the importance of the genes in this region.
Mechanisms of Deletion Formation
The formation of the 1p36 deletion primarily occurs through spontaneous genetic events. Most cases, approximately 80% to 95%, are de novo mutations, meaning they are new, random occurrences and are not inherited from either parent. These spontaneous deletions typically arise during the formation of reproductive cells, such as eggs or sperm, or during the very early stages of embryonic development. Affected individuals usually have no prior family history of the disorder.
In a smaller proportion of cases, about 5% to 20%, the 1p36 deletion is inherited from a parent. This happens when one parent carries a balanced chromosomal rearrangement, specifically a balanced translocation. A balanced translocation involves a rearrangement where pieces of chromosomes have broken off and reattached to other chromosomes, but no genetic material is gained or lost. Since there is no net gain or loss of genetic material, a parent with a balanced translocation usually does not experience health problems themselves.
However, when a parent with a balanced translocation produces reproductive cells, the chromosomes may not separate evenly. This can lead to an unbalanced translocation in the offspring, where there is either extra or missing genetic material. Offspring inheriting an unbalanced translocation will be missing the segment from the p arm of chromosome 1, resulting in the characteristic features of the disorder. While inherited cases are less common, genetic testing for parents is important to assess the risk for future pregnancies. There are no known environmental, dietary, or lifestyle factors that cause these deletions to occur.
Confirming the Genetic Cause
A definitive diagnosis of 1p36 deletion syndrome relies on specific genetic tests that detect the missing chromosomal segment. Clinical suspicion, based on observable features, often prompts these diagnostic procedures. Several advanced techniques confirm the presence and characterize the deletion.
Chromosomal microarray (CMA) is often the first-line diagnostic test, detecting small deletions and duplications across the entire genome. This high-resolution technique precisely identifies the size and exact breakpoints of the deleted region on chromosome 1p36. CMA provides detailed information about the extent of genetic loss, which helps in understanding the potential range of clinical manifestations.
Fluorescence In Situ Hybridization (FISH) is another technique used to confirm 1p36 deletion syndrome, often with strong clinical indication. FISH utilizes fluorescent probes designed to bind to specific DNA sequences on the chromosome. If the target sequence on one chromosome 1 copy is missing, the corresponding fluorescent signal will be absent or reduced, indicating a deletion. FISH can detect small deletions difficult to visualize with traditional methods.
Standard karyotyping, which involves visualizing chromosomes under a microscope, can also be used. While it might struggle to detect very small deletions, it can identify larger chromosomal abnormalities. Often, a combination of these tests, such as karyotyping followed by FISH or CMA, provides a comprehensive genetic analysis and confirms the diagnosis. These tests establish a medical prognosis and provide genetic counseling to families.