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Case Reports
. 2025 Mar;197(3):e63929.
doi: 10.1002/ajmg.a.63929. Epub 2024 Nov 13.

Optical Genome Mapping (OGM) Identifies Multiple Structural Variants in a Case With Atypical Phelan-McDermid Syndrome

Erica L Macke  1 , Anthony R Miller  1 , Caitlyn M Colwell  1 , Maria Hernandez Gonzalez  1 , Jesse Hunter  1   2   3 , Lakshmi Prakruthi Rao Venkata  1 , Lauren Walker  4 , Gregory Wheeler  1 , Richard K Wilson  1   2 , Elaine R Mardis  1   2 , Katherine E Miller  1   2 , Mariam T Mathew  1   2   3 , Bimal P Chaudhari  1   2   5 , Yassmine Akkari  1   3
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Case Reports

Optical Genome Mapping (OGM) Identifies Multiple Structural Variants in a Case With Atypical Phelan-McDermid Syndrome

Erica L Macke et al. Am J Med Genet A. 2025 Mar.

Abstract

Here we describe a neonate exhibiting hypotonia, macrocephaly, renal cysts, and respiratory failure requiring tracheostomy and ventilator support. Genetic analysis via rapid genome sequencing (rGS) identified a loss on chromosome 4 encompassing polycystin-2 (PKD2) and a loss on chromosome 22 encompassing SH3 and Multiple Ankyrin Repeat Domains 3 (SHANK3), indicative of Phelan-McDermid syndrome. Further analysis via traditional karyotyping, Optical Genome Mapping (OGM), and PacBio long-read sequencing revealed a more complex landscape of chromosomal rearrangements in this individual, including a balanced 3;12 translocation, and an unbalanced 17;22 translocation. The proband's phenotypic presentation is thought to be the result of Phelan-McDermid syndrome and represents an expansion of the described phenotypes to include significant respiratory failure. This study underscores the challenges and importance of comprehensive genetic testing in elucidating complex presentations and highlights the need for complementary testing methods to overcome limitations in resolution.

Keywords: Phelan‐McDermid Syndrome; long‐read Sequencing; optical Genome Mapping; rapid Genome Sequencing.

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References

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