Aortic Root Dilation and Genotype Associations in Phelan-McDermid Syndrome.

Phelan-McDermid syndrome (PMS) is a rare genetic neurodevelopmental disorder that results from the loss of one functional copy of the SHANK3 gene. While many clinical features of PMS are well-understood, there is currently limited literature on cardiovascular abnormalities in PMS. This report aims to evaluate the prevalence of aortic root dilation (ARD) among individuals with PMS and to understand if underlying genetic variation relates to risk for ARD. We present findings from 59 participants collected from a multisite observational study evaluating the phenotype and natural history of PMS. Individual echocardiographic and genetic reports were analyzed for aortic root measurements and genetic variant data, respectively. Our a priori hypothesis was that participants with chromosome 22 deletions with hg19 start coordinates on or before 49,900,000 (larger deletions) would have more instances of ARD than participants with deletion start coordinates after 49,900,000 (smaller deletions). Eight participants (14%) had ARD, and its presence was statistically significantly associated with large deletions (p = 0.047). Relatedly, participants with ARD had significantly more genes deleted on chromosome 22 than participants without ARD (p = 0.013). These results could aid in the identification of individuals with PMS who are at higher risk for ARD.

Retrospective Analysis of Presymptomatic Treatment In Sturge-Weber Syndrome.

Background: Ninety percent of infants with Sturge-Weber syndrome (SWS) brain involvement have seizure onset before 2 years of age; this is associated with worse neurologic outcome. Presymptomatic treatment before seizure onset may delay seizure onset and improve outcome, as has been shown in other conditions with a high-risk of developing epilepsy such as tuberous sclerosis complex. Electroencephalogram (EEG) may be a biomarker to predict seizure onset. This retrospective clinical data analysis aims to assess impact of presymptomatic treatment in SWS. Methods: This two-centered, IRB-approved, retrospective study analyzed records from patients with SWS brain involvement. Clinical data recorded included demographics, age of seizure onset (if present), brain involvement extent (unilateral versus bilateral), port-wine birthmark (PWB) extent, family history of seizure, presymptomatic treatment if received, neuroscore, and anti-seizure medication. EEG reports prior to seizure onset were analyzed. Results: Ninety-two patients were included (48 females), and 32 received presymptomatic treatment outside of a formal protocol (5 aspirin, 16 aspirin and levetiracetam; 9 aspirin and oxcarbazepine, 2 valproic acid). Presymptomatically-treated patients were more likely to be seizure-free at 2 years (15 of 32; 47% versus 7 of 60; 12%; p<.001). A greater percentage of presymptomatically-treated patients had bilateral brain involvement (38% treated versus 17% untreated; p=.026). Median hemiparesis neuroscore at 2 years was better in presymptomatically-treated patients. In EEG reports prior to seizure onset, the presence of slowing, epileptiform discharges, or EEG-identified seizures was associated with seizure onset by 2 (p=.001). Conclusion: Presymptomatic treatment is a promising approach to children diagnosed with SWS prior to seizure onset. Further study is needed, including prospective drug trials, long-term neuropsychological outcome, and prospective EEG analysis to assess this approach and determine biomarkers for presymptomatic treatment.