How Phelan-McDermid Syndrome Is Diagnosed
Who Should Be Tested
A Phelan-McDermid syndrome (PMS) diagnosis should be considered in individuals with intellectual disability with or without autism and/or atypical physical features. It should also be considered in individuals with severe speech delay or a history of neonatal hypotonia (low muscle tone) of unknown cause, or regression. Your medical professional will order the appropriate genetic diagnostic tests.
Tests Used For Diagnosis
These tests are most commonly used to diagnose Phelan-McDermid syndrome (PMS):
Chromosomal Microarray Analysis (CMA)
Chromosomal Microarray Analysis (CMA) is a genetic test that is most commonly used to diagnose PMS and involves only providing a small amount of blood. This technology can detect chromosomal deletions or duplications, however, these tests cannot ‘see’ the structure of the chromosome so they will not reveal if a translocation or ring chromosome is present.
Chromosome structural tests – FISH/karyotype
Other tests, called fluorescence in situ hybridization (FISH) or conventional chromosome analysis (karyotype) may detect larger deletions and visualize the structure of the chromosome. This type of test is necessary to identify translocations (unusual rearrangements) or ring chromosomes (an unusual formation of a chromosome into a ring shape). These tests can also be used to study parents of individuals with PMS to determine if either parent carries an unusual rearrangement in their chromosome 22 which could affect their child.
Sequencing – Whole Genome and Whole Exome
Sequencing is a way of reading the genome at a very high resolution, to report exactly what genes, and versions of genes, are present. Whole Exome Sequencing (WES) focuses on the genes that are involved in making proteins, which make up many of the functions in our cells. Whole Genome Sequencing (WGS) will read every single gene in the genome, including those that are involved in regulating other genes, and is the most complete sequencing method. Because sequencing reads every “base” or letter of these genes, it can be used to detect very small mutations (alterations), such as in the SHANK3 gene. These tests can also provide detailed information for the scientific and medical study of which genes matter in PMS.
Please refer to the diagram below or click on the following link that corresponds with the language of your choice, to help you and your doctor decide if follow-up testing is warranted.
Source: Catalina Betancur, MD, PhD, v1, with updates by Katy Phelan, et al. v2, 11/22 based on this publication.