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Neurologic features typically include intellectual disability, autism spectrum disorder, hypotonia, and absent speech, though there is considerable variability even among individuals with the same molecular cause. This prospective study aimed to explore the utility of genome sequencing to identify additional molecular diagnoses that may contribute to variability in a cohort of patients with PMS. Twenty probands diagnosed with PMS (60% with a 22q13 deletion, 40% with a <jats:italic>SHANK3<\/jats:italic> variant) underwent trio or duo genome sequencing and chromosomal microarray. This analysis identified a second molecular finding associated with a neurological condition in 3\/20 participants. Molecular diagnoses related to neurological phenotypes included: (1) spinal muscular atrophy, lower extremity\u2010predominant, 2A, autosomal dominant (SMALED2A), (2) spastic paraplegia 7, and (3) 16p11.2 deletion syndrome. Five additional new molecular diagnoses were associated with a clinically actionable secondary or incidental finding. This exploratory study provides early evidence for the potential utility of expanded sequencing among individuals with PMS, even for those without phenotypic features outside of the expected range.<\/jats:p>","DOI":"10.1002\/ajmg.b.33036","type":"journal-article","created":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T10:10:16Z","timestamp":1751191816000},"page":"126-134","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genome Sequencing Uncovers Additional Findings in Phelan\u2010<scp>McDermid<\/scp> Syndrome"],"prefix":"10.1002","volume":"198","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8253-5441","authenticated-orcid":false,"given":"Rachel Gore","family":"Moses","sequence":"first","affiliation":[{"name":"Centralized Sequencing Program National Institute of Allergy and Infectious Diseases, National Institutes of Health  Bethesda Maryland 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