About

Adeline Vanderver, M.D., is a Professor of Neurology in the Department of Neurology at the Perelman School of Medicine at the University of Pennsylvania. She serves as the Program Director of the Leukodystrophy Center of Excellence at the Children’s Hospital of Philadelphia and holds the Jacob A. Kamens Endowed Chair in Neurological Disorders and Translational NeuroTherapeutics. Her research focuses on leukodystrophies and neurogenetic disorders, with an emphasis on clinical characterization, genotype-phenotype correlations, and the development of diagnostic and therapeutic strategies. Dr. Vanderver has contributed to the understanding of Aicardi-Goutières syndrome, POLR3-related disorders, and mitochondrial deletion syndromes, among other neurogenetic conditions.

Research topics

• Medicine
• Biology
• Internal medicine
• Pediatrics
• Genetics
• Bioinformatics
• Pathology
• Endocrinology
• Radiology
• Psychiatry
• Biochemistry
• Computational biology
• Immunology

Selected publications

• Genetic and phenotypic spectrum associated with IFIH1 gain‐of‐function

  Human Mutation · 2020 · 111 citations

  • Biology
  • Genetics

  IFIH1 gain-of-function has been reported as a cause of a type I interferonopathy encompassing a spectrum of autoinflammatory phenotypes including Aicardi-Goutières syndrome and Singleton Merten syndrome. Ascertaining patients through a European and North American collaboration, we set out to describe the molecular, clinical and interferon status of a cohort of individuals with pathogenic heterozygous mutations in IFIH1. We identified 74 individuals from 51 families segregating a total of 27 likely pathogenic mutations in IFIH1. Ten adult individuals, 13.5% of all mutation carriers, were clinically asymptomatic (with seven of these aged over 50 years). All mutations were associated with enhanced type I interferon signaling, including six variants (22%) which were predicted as benign according to multiple in silico pathogenicity programs. The identified mutations cluster close to the ATP binding region of the protein. These data confirm variable expression and nonpenetrance as important characteristics of the IFIH1 genotype, a consistent association with enhanced type I interferon signaling, and a common mutational mechanism involving increased RNA binding affinity or decreased efficiency of ATP hydrolysis and filament disassembly rate.

  DOI

• <scp>MRI</scp> surveillance of boys with X‐linked adrenoleukodystrophy identified by newborn screening: Meta‐analysis and consensus guidelines

  Journal of Inherited Metabolic Disease · 2020 · 80 citations

  • Medicine
  • Pediatrics
  • Radiology

  BACKGROUND: Among boys with X-Linked adrenoleukodystrophy, a subset will develop childhood cerebral adrenoleukodystrophy (CCALD). CCALD is typically lethal without hematopoietic stem cell transplant before or soon after symptom onset. We sought to establish evidence-based guidelines detailing the neuroimaging surveillance of boys with neurologically asymptomatic adrenoleukodystrophy. METHODS: To establish the most frequent age and diagnostic neuroimaging modality for CCALD, we completed a meta-analysis of relevant studies published between January 1, 1970 and September 10, 2019. We used the consensus development conference method to incorporate the resulting data into guidelines to inform the timing and techniques for neuroimaging surveillance. Final guideline agreement was defined as >80% consensus. RESULTS: One hundred twenty-three studies met inclusion criteria yielding 1285 patients. The overall mean age of CCALD diagnosis is 7.91 years old. The median age of CCALD diagnosis calculated from individual patient data is 7.0 years old (IQR: 6.0-9.5, n = 349). Ninety percent of patients were diagnosed between 3 and 12. Conventional MRI was most frequently reported, comprised most often of T2-weighted and contrast-enhanced T1-weighted MRI. The expert panel achieved 95.7% consensus on the following surveillance parameters: (a) Obtain an MRI between 12 and 18 months old. (b) Obtain a second MRI 1 year after baseline. (c) Between 3 and 12 years old, obtain a contrast-enhanced MRI every 6 months. (d) After 12 years, obtain an annual MRI. CONCLUSION: Boys with adrenoleukodystrophy identified early in life should be monitored with serial brain MRIs during the period of highest risk for conversion to CCALD.

  DOI

• Clinical sites of the Undiagnosed Diseases Network: unique contributions to genomic medicine and science

  Genetics in Medicine · 2020 · 42 citations

  • Medicine
  • Computational biology
  • Genetics
  DOI

• Associations of paediatric demyelinating and encephalitic syndromes with myelin oligodendrocyte glycoprotein antibodies: a multicentre observational study

  The Lancet Neurology · 2020 · 319 citations

  • Medicine
  • Pediatrics
  • Immunology
  DOI

• An autosomal dominant neurological disorder caused by de novo variants in FAR1 resulting in uncontrolled synthesis of ether lipids

  Genetics in Medicine · 2020 · 49 citations

  • Medicine
  • Biology
  • Internal medicine
  DOI

Recent grants

• Improved Outcome Assessments in Adrenomyeloneuropathy

  NIH · $1.6M

• Project 1: Longitudinal Natural History Studies of Leukodystrophies

  NIH · $19.1M · 2019–2030

• NIH Grant K08NS060695

  NIH · $643k · 2014

• Reverse Transcriptase Inhibitors in Aicardi Goutieres Syndrome

  NIH · $1.6M · 2014–2020

Frequent coauthors

• Marjo S. van der Knaap

  Emma Kinderziekenhuis

  421 shared

• Nicole I. Wolf

  Emma Kinderziekenhuis

  369 shared

• Geneviève Bernard

  McGill University

  233 shared

• Guy Helman

  Royal Children's Hospital

  197 shared

• Truus E. M. Abbink

  Amsterdam Neuroscience

  194 shared

• Raphael Schiffmann

  Texas Christian University

  173 shared

• Enrico Bertini

  Bambino Gesù Children's Hospital

  157 shared

• Yanick J. Crow

  University of Edinburgh

  145 shared

Education

• M.D.

  Universite Catholique de Louvain Brussels

  1998

• Other

  Facultés Universitaires Notre Dame de la Paix Namur

  1994

Awards & honors

• Jacob A. Kamens Endowed Chair in Neurological Disorders and…
• Program Director of the Leukodystrophy Center of Excellence

Similar researchers at University of Pennsylvania

• John Q. Trojanowskih-296
• Craig B. Thompsonh-277
• Daniel J Raderh-236
• Carl H. Juneh-218
• M. Celeste Simonh-185