How is Warburg Micro (SPG69) diagnosed?
Warburg Micro Diagnosis
Diagnosis is usually made after finding two mutations of the same gene:
RAB3GAP1, RAB3GAP2, RAB18 or TBC1D20.
A whole exome sequence ordered by a geneticist is typically required.
Warburg Micro Syndrome may also be suspected when a clinician feels symptoms align with those of the disorder.
Clinicians should consult the diagnostic criteria here.
Where can I find genetic testing?
The Medical College of Wisconsin
The Medical College of Wisconsin offers free genetic testing via Semina Labs.
They are focused on understanding the genetic causes of eye anomalies, including cataract causing mutations for individuals in the US.
Read more here.
Invitae is a genetic testing company offers a la cart genetic testing. If a gene is identified, immediate family members can be tested for free.
The cataract panel tests for three of four Warburg micro causing genes, among other cataract causing genes and disorders.
Read more here.
*A required genetic consult is done via telehealth.
What if they don't find any of these genes?
In a study of 144 people with suspected Warburg Micro Syndrome, the four genes known to cause WMS were found in only 53% of cases.
This may mean that there are other genes that cause Warburg Micro Syndrome that have not yet been discovered.
Handley M, Sheridan E. RAB18 Deficiency. In: GeneReviews®. University of Washington, Seattle, Seattle (WA); 1993. PMID: 29300443. https://www.ncbi.nlm.nih.gov/books/NBK475670/
Handley, M. T., Morris-Rosendahl, D. J., Brown, S., Macdonald, F., Hardy, C., Bem, D., Carpanini, S. M., Borck, G., Martorell, L., Izzi, C., Faravelli, F., Accorsi, P., and 23 others. Mutation spectrum in RAB3GAP1, RAB3GAP2, and RAB18 and genotype-phenotype correlations in Warburg Micro syndrome and Martsolf syndrome. Hum. Mutat. 34: 686-696, 2013.
Liegel RP, Handley MT, Ronchetti A, Brown S, Langemeyer L, Linford A, et al. Loss-of-function mutations in TBC1D20 cause cataracts and male infertility in blind sterile mice and Warburg micro syndrome in humans. Am J Hum Genet. 2013;93(6):1001–14. https://doi.org/10.1016/j.ajhg.2013.10.011.
Last updated: 6/24/ 2022
Disclaimer: Families should consult a medical professional for genetic diagnosis, management and health concerns. We provide external links to help families and caregivers find additional information- this should not imply our endorsement or responsibility for their content.