About

Dr. Lucy Swanson is an Associate Professor of French and Caribbean Studies at the University of Arizona. She earned her PhD from the University of Pennsylvania in 2012. Her research examines how historical narratives and political discourse are reflected in recent francophone literary and visual culture, with a particular focus on Haiti and the French Antilles. Dr. Swanson has contributed to the academic field through articles published in journals such as the Cincinnati Romance Review, International Journal of Francophone Studies, and SITES: Contemporary French and Francophone Studies. She is also the author of the forthcoming book, The Zombie in Contemporary French Caribbean Fiction, which explores how contemporary writers and artists reinvent the folkloric figure of the zombie. Her scholarly work includes analyses of female resistance, magical thinking, sorcery, and the spatial imaginary in Haitian and Francophone Caribbean fiction, emphasizing themes of resistance, cultural identity, and social uprisings.

Research topics

• Medicine
• Pediatrics
• Internal medicine
• Psychiatry
• Biology
• Genetics
• Bioinformatics
• Intensive care medicine

Selected publications

• The natural history of CDKL5 deficiency disorder into adulthood

  medRxiv · 2025-01-14 · 2 citations

  preprintOpen access

  deficiency disorder (CDD) is limited to the results of cross-sectional analysis of largely pediatric cohorts. Assessment of outcomes in adulthood is critical for clinical decision-making and future precision medicine approaches but is challenging because of the diagnostic gap and duration of follow-up that would be required for prospective studies. We aimed to delineate the natural history retrospectively from adulthood. We analyzed clinical data about an international cohort of 67 adults with CDD. We analyzed demographic, phenotypic, CDKL5 Developmental Score (CDS), and treatment data, and tested associations with genetic factors, sex, and a positive or negative history of neonatal seizures, as an early predictor of prognosis. All but one of 67 adults (55 females, median age of 24 years at last follow-up) had epilepsy, typically beginning with epileptic spasms or tonic seizures before 4 months of age. Focal-onset and non-motor seizures emerged later. Fewer than a third had been documented as having bilateral tonic-clonic seizures or status epilepticus. Seizures often improved with age, but 73% had never experienced more than 6 months of seizure-freedom. Clobazam, sodium valproate, and lamotrigine were the most frequently prescribed antiseizure medications, but no specific treatment demonstrated superiority. Common comorbidities included movement disorders, visual impairment, sleep disorders, constipation, and scoliosis. All participants had intellectual disability, 75% had not acquired speech and 45% had regressed developmentally. 16% never achieved any CDS skill, but most attained at least three, and 28% attained six or all seven. By adulthood, half of those who had achieved any CDS skill retained all their CDS skills. The skills most frequently lost were independent walking and standing. Those with a history of neonatal seizures tended to attain fewer CDS skills and were more likely to have abnormal muscle tone in adulthood, atrioventricular conduction delay, and potential complications of their illness and treatment. Individuals carrying missense variants attained more CDS skills than those with other variants and were more likely to lose skills in adulthood and develop anxiety, possibly reflecting the limited neurodevelopment of those with non-missense variants, who manifested a more multisystemic disorder. In summary, retrospective data from adulthood elucidates the evolution of symptoms, variation in developmental outcomes, and the treatment landscape in CDKL5 deficiency disorder. Presence a non-missense variants or a history of neonatal seizures indicates a more complex disorder and lower developmental trajectory. Our findings will inform management decisions, prognostication, and the design of clinical trials in CDKL5 Deficiency Disorder.

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• Investigating the neuronal role of the proteasomal ATPase subunit gene PSMC5 in neurodevelopmental proteasomopathies

  Nature Communications · 2025-11-26 · 2 citations

  articleOpen access

  Neurodevelopmental proteasomopathies are a group of disorders caused by variants in proteasome subunit genes, that disrupt protein homeostasis and brain development through poorly characterized mechanisms. Here, we report 26 distinct variants in PSMC5, encoding the AAA⁺ ATPase subunit PSMC5/RPT6, in individuals with syndromic neurodevelopmental conditions. Combining genetic, multi-omics and biochemical approaches across cellular models and Drosophila, we unveil the essential role of proteasomes in sustaining key cellular processes. Loss of PSMC5/RPT6 function impairs proteasome activity, leading to protein aggregation, disruption of mitochondrial homeostasis, and dysregulation of lipid metabolism and immune signaling. It also compromises synaptic balance, neuritogenesis, and neural progenitor cell stemness, causing deficits in higher-order functions, including learning and locomotion. Pharmacological targeting of integrated stress response kinases reveals a mechanistic link between proteotoxic stress and spontaneous type I interferon activation. These findings expand our understanding of proteasome-dependent quality control in neurodevelopment and suggest potential therapeutic strategies for neurodevelopmental proteasomopathies.

  PublisherOA PDFDOI

• Unveiling the crucial neuronal role of the proteasomal ATPase subunit gene <i>PSMC5</i> in neurodevelopmental proteasomopathies

  medRxiv · 2024-01-16 · 6 citations

  preprintOpen access

  Abstract Neurodevelopmental proteasomopathies represent a distinctive category of neurodevelopmental disorders (NDD) characterized by genetic variations within the 26S proteasome, a protein complex governing eukaryotic cellular protein homeostasis. In our comprehensive study, we identified 23 unique variants in PSMC5 , which encodes the AAA-ATPase proteasome subunit PSMC5/Rpt6, causing syndromic NDD in 38 unrelated individuals. Overexpression of PSMC5 variants altered human hippocampal neuron morphology, while PSMC5 knockdown led to impaired reversal learning in flies and loss of excitatory synapses in rat hippocampal neurons. PSMC5 loss-of-function resulted in abnormal protein aggregation, profoundly impacting innate immune signaling, mitophagy rates, and lipid metabolism in affected individuals. Importantly, targeting key components of the integrated stress response, such as PKR and GCN2 kinases, ameliorated immune dysregulations in cells from affected individuals. These findings significantly advance our understanding of the molecular mechanisms underlying neurodevelopmental proteasomopathies, provide links to research in neurodegenerative diseases, and open up potential therapeutic avenues.

  PublisherOA PDFDOI

• Bipolar Disorder in a female with CDKL5 Deficiency Disorder: A Case Report

  Research Square · 2024-09-10 · 1 citations

  preprintOpen access
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• Deletions in the <i>CDKL5</i> 5′ untranslated region lead to CDKL5 deficiency disorder

  American Journal of Medical Genetics Part A · 2024-08-28 · 2 citations

  articleOpen access

  Pathogenic variants in the cyclin-dependent kinase-like 5 (CDKL5) gene are associated with CDKL5 deficiency disorder (CDD), a severe X-linked developmental and epileptic encephalopathy. Deletions affecting the 5' untranslated region (UTR) of CDKL5, which involve the noncoding exon 1 and/or alternatively spliced first exons (exons 1a-e), are uncommonly reported. We describe genetic and phenotypic characteristics for 15 individuals with CDKL5 partial gene deletions affecting the 5' UTR. All individuals presented characteristic features of CDD, including medically refractory infantile-onset epilepsy, global developmental delay, and visual impairment. We performed RNA sequencing on fibroblast samples from three individuals with small deletions involving exons 1 and/or 1a/1b only. Results demonstrated reduced CDKL5 mRNA expression with no evidence of expression from alternatively spliced first exons. Our study broadens the genotypic spectrum for CDD by adding to existing evidence that deletions affecting the 5' UTR of the CDKL5 gene are associated with the disorder. We propose that smaller 5' UTR deletions may require additional molecular testing approaches such as RNA sequencing to determine pathogenicity.

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• Cohort Expansion and Genotype-Phenotype Analysis of RAB11A-Associated Neurodevelopmental Disorder

  Pediatric Neurology · 2024-07-20 · 2 citations

  articleOpen access
  PublisherOA PDFDOI

• Comparison of evoked potentials across four related developmental encephalopathies

  Journal of Neurodevelopmental Disorders · 2023-03-04 · 22 citations

  articleOpen access

  BACKGROUND: Developing biomarkers is a priority for drug development for all conditions, but vital in the rare neurodevelopmental disorders where sensitive outcome measures are lacking. We have previously demonstrated the feasibility and tracking of evoked potentials to disease severity in Rett syndrome and CDKL5 deficiency disorder. The aim of the current study is to characterize evoked potentials in two related developmental encephalopathies, MECP2 duplication syndrome and FOXG1 syndrome, and compare across all four groups to better understand the potential of these measures to serve as biomarkers of clinical severity for the developmental encephalopathies. METHODS: Visual and auditory evoked potentials were acquired from participants with MECP2 duplication syndrome and FOXG1 syndrome across five sites of the Rett Syndrome and Rett-Related Disorders Natural History Study. A group of age-matched individuals (mean = 7.8 years; range = 1-17) with Rett syndrome, CDKL5 deficiency disorder, and typically-developing participants served as a comparison group. The analysis focused on group-level differences as well as associations between the evoked potentials and measures of clinical severity from the Natural History Study. RESULTS: As reported previously, group-level comparisons revealed attenuated visual evoked potentials (VEPs) in participants with Rett syndrome (n = 43) and CDKL5 deficiency disorder (n = 16) compared to typically-developing participants. VEP amplitude was also attenuated in participants with MECP2 duplication syndrome (n = 15) compared to the typically-developing group. VEP amplitude correlated with clinical severity for Rett syndrome and FOXG1 syndrome (n = 5). Auditory evoked potential (AEP) amplitude did not differ between groups, but AEP latency was prolonged in individuals with MECP2 duplication syndrome (n = 14) and FOXG1 syndrome (n = 6) compared to individuals with Rett syndrome (n = 51) and CDKL5 deficiency disorder (n = 14). AEP amplitude correlated with severity in Rett syndrome and CDKL5 deficiency disorder. AEP latency correlated with severity in CDKL5 deficiency disorder, MECP2 duplication syndrome, and FOXG1 syndrome. CONCLUSIONS: There are consistent abnormalities in the evoked potentials in four developmental encephalopathies some of which correlate with clinical severity. While there are consistent changes amongst these four disorders, there are also condition specific findings that need to be further refined and validated. Overall, these results provide a foundation for further refinement of these measures for use in future clinical trials for these conditions.

  PublisherOA PDFDOI

• Epileptic spasms in CDKL5 deficiency disorder: Delayed treatment and poor response to first‐line therapies

  Epilepsia · 2023-04-28 · 10 citations

  articleOpen access

  OBJECTIVE: We aimed to assess the treatment response of infantile-onset epileptic spasms (ES) in CDKL5 deficiency disorder (CDD) vs other etiologies. METHODS: We evaluated patients with ES from the CDKL5 Centers of Excellence and the National Infantile Spasms Consortium (NISC), with onset from 2 months to 2 years, treated with adrenocorticotropic hormone (ACTH), oral corticosteroids, vigabatrin, and/or the ketogenic diet. We excluded children with tuberous sclerosis complex, trisomy 21, or unknown etiology with normal development because of known differential treatment responses. We compared the two cohorts for time to treatment and ES remission at 14 days and 3 months. RESULTS: We evaluated 59 individuals with CDD (79% female, median ES onset 6 months) and 232 individuals from the NISC database (46% female, median onset 7 months). In the CDD cohort, seizures prior to ES were common (88%), and hypsarrhythmia and its variants were present at ES onset in 34%. Initial treatment with ACTH, oral corticosteroids, or vigabatrin started within 1 month of ES onset in 27 of 59 (46%) of the CDD cohort and 182 of 232 (78%) of the NISC cohort (p < .0001). Fourteen-day clinical remission of ES was lower for the CDD group (26%, 7/27) than for the NISC cohort (58%, 106/182, p = .0002). Sustained ES remission at 3 months occurred in 1 of 27 (4%) of CDD patients vs 96 of 182 (53%) of the NISC cohort (p < .0001). Comparable results were observed with longer lead time (≥1 month) or prior treatment. Ketogenic diet, used within 3 months of ES onset, resulted in ES remission at 1 month, sustained at 3 months, in at least 2 of 13 (15%) individuals with CDD. SIGNIFICANCE: Compared to the broad group of infants with ES, children with ES in the setting of CDD often experience longer lead time to treatment and respond poorly to standard treatments. Development of alternative treatments for ES in CDD is needed.

  PublisherOA PDFDOI

• Genetic Diagnosis Impacts Medical Management for Pediatric Epilepsies

  Pediatric Neurology · 2022-10-26 · 27 citations

  articleOpen access
  PublisherOA PDFDOI

• Convergent cerebrospinal fluid proteomes and metabolic ontologies in humans and animal models of Rett syndrome

  iScience · 2022-08-17 · 15 citations

  articleOpen access

  MECP2 loss-of-function mutations cause Rett syndrome, a neurodevelopmental disorder resulting from a disrupted brain transcriptome. How these transcriptional defects are decoded into a disease proteome remains unknown. We studied the proteome of Rett cerebrospinal fluid (CSF) to identify consensus Rett proteome and ontologies shared across three species. Rett CSF proteomes enriched proteins annotated to HDL lipoproteins, complement, mitochondria, citrate/pyruvate metabolism, synapse compartments, and the neurosecretory protein VGF. We used shared Rett ontologies to select analytes for orthogonal quantification and functional validation. VGF and ontologically selected CSF proteins had genotypic discriminatory capacity as determined by receiver operating characteristic analysis in Mecp2 -/y and Mecp2 /+ . Differentially expressed CSF proteins distinguished Rett from a related neurodevelopmental disorder, CDKL5 deficiency disorder. We propose that Mecp2 mutant CSF proteomes and ontologies inform putative mechanisms and biomarkers of disease. We suggest that Rett syndrome results from synapse and metabolism dysfunction.

  PublisherOA PDFDOI

Frequent coauthors

• Alan H. Beggs

  260 shared

• Özge Ceyhan-Birsoy

  Memorial Sloan Kettering Cancer Center

  223 shared

• Pankaj B. Agrawal

  University of Miami

  206 shared

• Henk Granzier

  University of Arizona

  205 shared

• Michael W. Lawlor

  200 shared

• Susan T. Iannaccone

  199 shared

• Carlos Hidalgo

  University of Arizona

  196 shared

• Klaus Schmitz‐Abe

  Harvard University

  196 shared