Genetics and the Microarray Report

Understanding a genetic report is like learning to read a map of unique DNA. For Proximal 18q Deletion Syndrome, the most important document you will receive is the results of a Chromosomal Microarray Analysis (CMA) or array-CGH ^[1]. Unlike older tests that just looked at chromosomes under a microscope, these modern tests can find tiny, submicroscopic missing pieces of genetic material that were previously invisible ^[2][3].

How the Diagnosis is Made

A Chromosomal Microarray (CMA) is the clinical standard for diagnosing developmental delays and genetic syndromes ^[4]. It works by comparing DNA to a “normal” reference sample to find copy number variants (CNVs)—sections where DNA is missing or extra ^[5]. In the case of Proximal 18q-, the report will show a deletion (a loss of one copy) in a specific region of the long arm (q) of chromosome 18.

Reading the Coordinates (Breakpoints)

Every genetic report uses a specific “address” to describe exactly where the deletion starts and ends. These are called breakpoints.

• The Region: Proximal 18q deletions typically occur between the addresses 18q11.2 and 18q21.1 ^[6]. (If your report shows a deletion at 18q23, that is a distal deletion, which has a different medical profile).
• The Coordinates: You will see long strings of numbers (e.g., 18:18,500,000-43,500,000). These numbers change depending on which “map” version (called a Genome Build, such as GRCh37/hg19 or GRCh38/hg38) the lab used ^[7].
• Size vs. Location: Deletion size is measured in Mb (megabases, or millions of letters) or kb (kilobases, or thousands of letters). While larger deletions often involve more genes, the location of the deletion is the most important factor because certain genes in the proximal region are critical for normal development ^[8].

Key Genes of Interest in the Proximal Region

The symptoms experienced are directly linked to the specific genes missing in the deleted region.

• GATA6 (18q11.2): This gene is a critical driver for heart development. Missing this gene (a state called haploinsufficiency) is strongly associated with structural heart defects, specifically conotruncal defects ^[6]. If this gene is deleted, cardiac screening is absolutely vital.
• TCF4 (18q21.2): Located near the end of the proximal region, this is a “dosage-sensitive” gene. If this gene is missing, it causes Pitt-Hopkins Syndrome ^[9]. Individuals whose deletions extend into this area may show characteristic features like a wide mouth, distinct nasal bridge, breathing anomalies, and more significant intellectual disability ^[10][11].
• SETBP1 (18q21.1): Deletions involving this gene are strongly associated with intellectual disability and severe expressive speech delays ^[6].

Note: Some online resources mention the MBP gene causing white matter issues, or the SALL3 gene. It is critical to know that those genes are located at the tip of the chromosome (18q23) and are features of Distal 18q Deletion Syndrome, not Proximal.

Genetic Report Checklist

When looking at the report, ensure it contains these four critical pieces of information:

1. Breakpoints: The exact start and end coordinates (e.g., 18:19.6 Mb – 24.4 Mb) ^[7].
2. Genome Build: Which map was used (e.g., hg19/GRCh37 or hg38/GRCh38) ^[7].
3. Total Size: The total amount of missing material (e.g., 5.2 Mb) ^[12].
4. Medically Significant Genes: A list of known genes (often called OMIM genes) included in that specific deleted section ^[13].

By identifying these specifics, the medical team can better predict which health areas—like the heart or neurological development—need the most attention ^[6][14].