1p36 Deletion Syndrome is a neurodevelopmental disorder caused by the loss of a small segment of genetic material from one of the body’s largest chromosomes. It affects an estimated one in 5,000 to 10,000 live births. This loss of genetic code leads to a range of challenges, including intellectual disability, developmental delay, and structural abnormalities. Understanding the causes requires examining the specific location of the missing material and the two primary mechanisms by which this chromosomal abnormality occurs.
The Specific Genetic Change
The cause of 1p36 Deletion Syndrome involves a segment missing from chromosome 1, the largest human chromosome. The name “1p36” refers to chromosome 1, the short arm (“p”), and band location 36, which is near the very end of the arm.
The genetic event is a deletion, resulting in the loss of numerous genes in that region. Because the missing segment is at the furthest tip, it is described as a “terminal deletion.” This loss means the individual has only one copy of the genes in the 1p36 region instead of the usual two, a state known as haploinsufficiency.
The size of the deleted segment varies significantly, ranging from approximately 1.5 million to over 10 million base pairs. The specific genes lost, such as RERE, GABRD, and SKI, determine the symptoms and severity. While most cases involve a simple terminal deletion, some individuals have interstitial deletions or more complex rearrangements.
Spontaneous (De Novo) Origin
The majority of 1p36 Deletion Syndrome cases arise spontaneously (de novo), meaning the deletion is a new genetic event not present in either parent’s DNA. Approximately 80% of all diagnoses fall into this category, where the mutation occurs randomly.
This spontaneous change typically happens during the formation of reproductive cells (gametogenesis) or in the earliest stages of cell division shortly after fertilization. In these scenarios, the affected child is the first in the family to carry the deletion, and the parents have a typical chromosomal makeup.
The mechanism involves an error when the cell duplicates or separates chromosomes, resulting in a break and subsequent loss of the distal part of chromosome 1. This random event has no known association with environmental factors or family history. The risk of having a second child with the same spontaneous deletion is very low.
The Role of Parental Genetic Arrangements
A smaller proportion of 1p36 Deletion Syndrome diagnoses, around 20%, are inherited from a parent. This cause involves a parental genetic arrangement known as a balanced translocation. In this arrangement, a piece of chromosome 1 has broken off and swapped places with a segment from a different chromosome.
The parent carrying the balanced translocation is typically healthy because no genetic material is gained or lost; it is simply rearranged. However, errors arise during the production of egg or sperm cells. When these rearranged chromosomes separate into gametes, the process often yields cells with missing or extra genetic material.
If the parent passes on a chromosome 1 missing the 1p36 segment, the child inherits an unbalanced chromosome complement. This results in an “unbalanced translocation” causing the 1p36 deletion and the full syndrome. This inherited cause means the parents have an elevated recurrence risk for future pregnancies, related to the specific nature of the parent’s balanced translocation.
Determining the Cause Through Genetic Testing
Determining the precise cause of 1p36 Deletion Syndrome is necessary for accurate genetic counseling and family planning. The initial diagnosis is established using high-resolution genetic tests that detect the loss of DNA. Techniques like chromosomal microarray analysis (CMA) or fluorescence in situ hybridization (FISH) confirm the deletion in the 1p36 region.
The next step is parental genetic testing to determine the origin of the deletion. This testing, often involving karyotyping or CMA, differentiates between the two causal pathways. If both parents’ chromosomes are normal, the child’s deletion is confirmed as a de novo, or spontaneous, event.
If one parent carries a balanced translocation involving the 1p36 region, the cause is identified as inherited. This distinction informs the family about recurrence risk in subsequent pregnancies. For a de novo event, the risk is negligible, but for an inherited balanced translocation, the recurrence risk is substantially higher, necessitating detailed genetic counseling.