Heather C. Mefford, MD, PhD

Heather C. Mefford, MD, PhD


On staff since August 2008

Children's Title: Attending Physician

Academic Title: Associate Professor

Research Center: Center for Integrative Brain Research

"Geneticists are driven to understand the genetic basis of disease because we believe this information will lead us to better treatments and cures. I am so fortunate to be able to interact with a great group of researchers in Seattle who are using technology to understand disease. The scientists and the physicians I work with are very innovative and collaborative, which creates an inspiring, fun and successful working environment."

Heather C. Mefford, MD, PhD, is an assistant professor of pediatrics at the University of Washington in the Division of Genetic Medicine and attending physician at Seattle Children’s Hospital in the Medical Genetics Clinic. Dr. Mefford has a research laboratory devoted to the discovery of novel genomic disorders – conditions caused by small deletions or duplications (copy number changes) of DNA.

She has been involved in the discovery and characterization of several new genomic disorders, including deletions of chromosomes 1q21, 15q13 and 17q12, each of which cause a range of clinical features. She is continuing to investigate individuals with these conditions to better understand the variable outcomes. In addition, her research group uses state-of-the-art technology to discover new copy number changes that underlie a variety of pediatric conditions. Examples include neurocognitive disorders such as epilepsy and intellectual disability and congenital abnormalities including craniosynostosis and kidney defects. Dr. Mefford’s clinical interests parallel her research interests and include seeing patients with genomic disorders and patients with neurocognitive defects of unknown etiology. 

Making a Difference

  • Mentoring Talented Junior Faculty

    An academic medical center and research institute, Seattle Children’s is dedicated to helping junior faculty establish research careers. Recently, several of our emerging genetics researchers have made significant contributions to their field. ... cont.


Board Certification(s)

Clinical Genetics (MD)

Medical/Professional School

University of Washington, Seattle
University of Washington, Seattle, Medical Genetics


Pediatrics, Seattle Children's Hospital, Seattle


Medical Genetics, University of Washington, Seattle

Clinical Interests

Epilepsy genetics, microdeletion syndromes; chromosome rearrangements and copy number changes as a cause of birth defects, mental retardation or autism.

Awards and Honors

Award Name Award Description Awarded By Award Date
2013 Young Investigator Award Society for Pediatric Research 2013
Young Investigator Travel Award American Epilepsy Society Annual Meeting 2011
William K. Bowes, Jr. Award in Medical Genetics 2009
Finalist, American Society of Human Genetics Trainee Awards Competition, 2008 Annual Meeting, Postdoctoral Clinical Research Category 2008


  • Mefford HC, Rosenfeld JA, Shur N, Slavotinek AM, Cox VA, Hennekam RC, Firth HV, Willatt L, Wheeler P, Morrow EM, Cook J, Sullivan R, Oh A, McDonald MT, Zonana J, Keller K, Hannibal MC, Ball S, Kussmann J, Gorski J, Zelewski S, Banks V, Smith W, Smith R, Paull L, Rosenbaum KN, Amor DJ, Silva J, Lamb A, Eichler EE
    Further clinical and molecular delineation of the 15q24 microdeletion syndrome.
    22180641 Journal of medical genetics , 2012 Feb. : 49(2)110-8 PMCID: PMC3261729
  • Muhle H, Mefford HC, Obermeier T, von Spiczak S, Eichler EE, Stephani U, Sander T, Helbig I
    Absence seizures with intellectual disability as a phenotype of the 15q13.3 microdeletion syndrome.
    22050399 Epilepsia , 2011 Dec. : 52(12)e194-8 PMCID: PMC3270691
  • Mefford HC, Yendle SC, Hsu C, Cook J, Geraghty E, McMahon JM, Eeg-Olofsson O, Sadleir LG, Gill D, Ben-Zeev B, Lerman-Sagie T, Mackay M, Freeman JL, Andermann E, Pelakanos JT, Andrews I, Wallace G, Eichler EE, Berkovic SF, Scheffer IE
    Rare copy number variants are an important cause of epileptic encephalopathies.
    22190369 Annals of neurology , 2011 Dec. : 70(6)974-85 PMCID: PMC3245646
  • Hannibal MC, Buckingham KJ, Ng SB, Ming JE, Beck AE, McMillin MJ, Gildersleeve HI, Bigham AW, Tabor HK, Mefford HC, Cook J, Yoshiura K, Matsumoto T, Matsumoto N, Miyake N, Tonoki H, Naritomi K, Kaname T, Nagai T, Ohashi H, Kurosawa K, Hou JW, Ohta T, Liang D, Sudo A, Morris CA, Banka S, Black GC, Clayton-Smith J, Nickerson DA, Zackai EH, Shaikh TH, Donnai D, Niikawa N, Shendure J, Bamshad MJ
    Spectrum of MLL2 (ALR) mutations in 110 cases of Kabuki syndrome.
    21671394 American journal of medical genetics. Part A , 2011 July : 155A(7)1511-6 PMCID: PMC3121928
  • Sisodiya SM, Mefford HC
    Genetic contribution to common epilepsies.
    21252662 Current opinion in neurology , 2011 Apr, : 24(2)140-5
  • Mulley JC, Mefford HC
    Epilepsy and the new cytogenetics.
    21269290 Epilepsia , 2011 Mar. : 52(3)423-32 PMCID: PMC3079368
  • Cooper GM, Mefford HC
    Detection of copy number variation using SNP genotyping.
    21822880 Methods in molecular biology (Clifton, N.J.) , 2011 : 767243-52
  • Mefford HC, Mulley JC
    Genetically complex epilepsies, copy number variants and syndrome constellations.
    20923578 Genome medicine , 2010 Oct. 5 : 2(10)71 PMCID: PMC2988446
  • Ng SB, Bigham AW, Buckingham KJ, Hannibal MC, McMillin MJ, Gildersleeve HI, Beck AE, Tabor HK, Cooper GM, Mefford HC, Lee C, Turner EH, Smith JD, Rieder MJ, Yoshiura K, Matsumoto N, Ohta T, Niikawa N, Nickerson DA, Bamshad MJ, Shendure J
    Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome.
    20711175 Nature genetics , 2010 Sept. : 42(9)790-3 PMCID: PMC2930028
  • Mefford HC, Shafer N, Antonacci F, Tsai JM, Park SS, Hing AV, Rieder MJ, Smyth MD, Speltz ML, Eichler EE, Cunningham ML
    Copy number variation analysis in single-suture craniosynostosis: multiple rare variants including RUNX2 duplication in two cousins with metopic craniosynostosis.
    20683987 American journal of medical genetics. Part A , 2010 Sept. : 152A(9)2203-10 PMCID: PMC3104131
  • Bachmann-Gagescu R, Mefford HC, Cowan C, Glew GM, Hing AV, Wallace S, Bader PI, Hamati A, Reitnauer PJ, Smith R, Stockton DW, Muhle H, Helbig I, Eichler EE, Ballif BC, Rosenfeld J, Tsuchiya KD
    Recurrent 200-kb deletions of 16p11.2 that include the SH2B1 gene are associated with developmental delay and obesity.
    20808231 Genetics in medicine : official journal of the American College of Medical Genetics , 2010 Aug. 30
  • Mefford HC, Muhle H, Ostertag P, von Spiczak S, Buysse K, Baker C, Franke A, Malafosse A, Genton P, Thomas P, Gurnett CA, Schreiber S, Bassuk AG, Guipponi M, Stephani U, Helbig I, Eichler EE
    Genome-wide copy number variation in epilepsy: novel susceptibility loci in idiopathic generalized and focal epilepsies.
    20502679 PLoS genetics , 2010 May 20 : 6(5)e1000962 PMCID: PMC2873910
  • Girirajan S, Rosenfeld JA, Cooper GM, Antonacci F, Siswara P, Itsara A, Vives L, Walsh T, McCarthy SE, Baker C, Mefford HC, Kidd JM, Browning SR, Browning BL, Dickel DE, Levy DL, Ballif BC, Platky K, Farber DM, Gowans GC, Wetherbee JJ, Asamoah A, Weaver DD, Mark PR, Dickerson J, Garg BP, Ellingwood SA, Smith R, Banks VC, Smith W, McDonald MT, Hoo JJ, French BN, Hudson C, Johnson JP, Ozmore JR, Moeschler JB, Surti U, Escobar LF, El-Khechen D, Gorski JL, Kussmann J, Salbert B, Lacassie Y, Biser A, McDonald-McGinn DM, Zackai EH, Deardorff MA, Shaikh TH, Haan E, Friend KL, Fichera M, Romano C, Gécz J, DeLisi LE, Sebat J, King MC, Shaffer LG, Eichler EE
    A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay.
    20154674 Nature genetics , 2010 Mar. : 42(3)203-9 PMCID: PMC2847896
  • de Kovel CG, Trucks H, Helbig I, Mefford HC, Baker C, Leu C, Kluck C, Muhle H, von Spiczak S, Ostertag P, Obermeier T, Kleefuss-Lie AA, Hallmann K, Steffens M, Gaus V, Klein KM, Hamer HM, Rosenow F, Brilstra EH, Trenité DK, Swinkels ME, Weber YG, Unterberger I, Zimprich F, Urak L, Feucht M, Fuchs K, Møller RS, Hjalgrim H, De Jonghe P, Suls A, Rückert IM, Wichmann HE, Franke A, Schreiber S, Nürnberg P, Elger CE, Lerche H, Stephani U, Koeleman BP, Lindhout D, Eichler EE, Sander T
    Recurrent microdeletions at 15q11.2 and 16p13.11 predispose to idiopathic generalized epilepsies.
    19843651 Brain : a journal of neurology , 2010 Jan. : 133(Pt 1)23-32 PMCID: PMC2801323
  • Mefford HC
    Genotype to phenotype-discovery and characterization of novel genomic disorders in a "genotype-first" era.
    20010361 Genetics in medicine : official journal of the American College of Medical Genetics , 2009 Dec. : 11(12)836-42
  • Dibbens LM, Mullen S, Helbig I, Mefford HC, Bayly MA, Bellows S, Leu C, Trucks H, Obermeier T, Wittig M, Franke A, Caglayan H, Yapici Z, EPICURE Consortium, Sander T, Eichler EE, Scheffer IE, Mulley JC, Berkovic SF
    Familial and sporadic 15q13.3 microdeletions in idiopathic generalized epilepsy: precedent for disorders with complex inheritance.
    19592580 Human molecular genetics , 2009 Oct. 1 : 18(19)3626-31
  • Mefford HC, Cooper GM, Zerr T, Smith JD, Baker C, Shafer N, Thorland EC, Skinner C, Schwartz CE, Nickerson DA, Eichler EE
    A method for rapid, targeted CNV genotyping identifies rare variants associated with neurocognitive disease.
    19506092 Genome research , 2009 Sept. : 19(9)1579-85 PMCID: PMC2752120
  • Mefford HC, Eichler EE
    Duplication hotspots, rare genomic disorders, and common disease.
    19477115 Current opinion in genetics & development , 2009 June : 196-204
  • Landsverk ML, Ruzzo EK, Mefford HC, Buysse K, Buchan JG, Eichler EE, Petty EM, Peterson EA, Knutzen DM, Barnett K, Farlow MR, Caress J, Parry GJ, Quan D, Gardner KL, Hong M, Simmons Z, Bird TD, Chance PF, Hannibal MC
    Duplication within the SEPT9 gene associated with a founder effect in North American families with hereditary neuralgic amyotrophy.
    19139049 Human molecular genetics , 2009 Apr, 1 : 1200-8
  • Sparkes RL, Shetty S, Chernos JE, Mefford HC, Micheil Innes A
    Interstitial deletion of 11q in a mother and fetus: implications of directly transmitted chromosomal imbalances for prenatal genetic counseling.
    19177486 Prenatal diagnosis , 2009 Mar. : 283-6
  • Helbig I, Mefford HC, Sharp AJ, Guipponi M, Fichera M, Franke A, Muhle H, de Kovel C, Baker C, von Spiczak S, Kron KL, Steinich I, Kleefuss-Lie AA, Leu C, Gaus V, Schmitz B, Klein KM, Reif PS, Rosenow F, Weber Y, Lerche H, Zimprich F, Urak L, Fuchs K, Feucht M, Genton P, Thomas P, Visscher F, de Haan GJ, Møller RS, Hjalgrim H, Luciano D, Wittig M, Nothnagel M, Elger CE, Nürnberg P, Romano C, Malafosse A, Koeleman BP, Lindhout D, Stephani U, Schreiber S, Eichler EE, Sander T
    15q13.3 microdeletions increase risk of idiopathic generalized epilepsy.
    19136953 Nature genetics , 2009 Feb. : 160-2
  • Mefford HC, Sharp AJ, Baker C, Itsara A, Jiang Z, Buysse K, Huang S, Maloney VK, Crolla JA, Baralle D, Collins A, Mercer C, Norga K, de Ravel T, Devriendt K, Bongers EM, de Leeuw N, Reardon W, Gimelli S, Bena F, Hennekam RC, Male A, Gaunt L, Clayton-Smith J, Simonic I, Park SM, Mehta SG, Nik-Zainal S, Woods CG, Firth HV, Parkin G, Fichera M, Reitano S, Lo Giudice M, Li KE, Casuga I, Broomer A, Conrad B, Schwerzmann M, Räber L, Gallati S, Striano P, Coppola A, Tolmie JL, Tobias ES, Lilley C, Armengol L, Spysschaert Y, Verloo P, De Coene A, Goossens L, Mortier G, Speleman F, van Binsbergen E, Nelen MR, Hochstenbach R, Poot M, Gallagher L, Gill M, McClellan J, King MC, Regan R, Skinner C, Stevenson RE, Antonarakis SE, Chen C, Estivill X, Menten B, Gimelli G, Gribble S, Schwartz S, Sutcliffe JS, Walsh T, Knight SJ, Sebat J, Romano C, Schwartz CE, Veltman JA, de Vries BB, Vermeesch JR, Barber JC, Willatt L, Tassabehji M, Eichler EE
    Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes.
    18784092 The New England journal of medicine , 2008 Oct. 16 : 1685-99
  • Sharp AJ, Mefford HC, Li K, Baker C, Skinner C, Stevenson RE, Schroer RJ, Novara F, De Gregori M, Ciccone R, Broomer A, Casuga I, Wang Y, Xiao C, Barbacioru C, Gimelli G, Bernardina BD, Torniero C, Giorda R, Regan R, Murday V, Mansour S, Fichera M, Castiglia L, Failla P, Ventura M, Jiang Z, Cooper GM, Knight SJ, Romano C, Zuffardi O, Chen C, Schwartz CE, Eichler EE
    A recurrent 15q13.3 microdeletion syndrome associated with mental retardation and seizures.
    18278044 Nature genetics , 2008 Mar. : 322-8
  • Mefford HC, Clauin S, Sharp AJ, Moller RS, Ullmann R, Kapur R, Pinkel D, Cooper GM, Ventura M, Ropers HH, Tommerup N, Eichler EE, Bellanne-Chantelot C
    Recurrent reciprocal genomic rearrangements of 17q12 are associated with renal disease, diabetes, and epilepsy.
    17924346 American journal of human genetics , 2007 Nov. : 1057-69
  • Gygi MP, Ferguson MD, Mefford HC, Lund KP, O'Day C, Zhou P, Friedman C, van den Engh G, Stolowitz ML, Trask BJ
    Use of fluorescent sequence-specific polyamides to discriminate human chromosomes by microscopy and flow cytometry.
    12087162 Nucleic acids research , 2002 July 1 : 2790-9
  • Mefford HC, Trask BJ
    The complex structure and dynamic evolution of human subtelomeres.
    11836503 Nature reviews. Genetics , 2002 Feb. : 91-102


Presentations Title Event Location Date
CNVs in epilepsy, ASD and Intellectual disability International Child Neurology Conference Brisbane, Australia 2012
Microarrays and Whole Exome Sequencing Provide a Window into Developmental Brain Disorders Pediatric Academic Societies Annual Meeting Boston, MA 2012
New Insights into the evaluation of the individual with Interllectual Disability American College of Medical Genetics Annual CLinical Genetics Meeting Vancouver, WA March 2011
Genomic approaches to epilepsy: Copy number variants American Epilepsy Society Annual meeting Baltimore, MD 2011
CNVs in epilepsy Coming Together on Epilepsy Genetics Workshop Jackson Labs, Bar Harbor Maine 2011
Copy number variants in epilepsies Genomic Disorders Meeting Sanger Center, Hinxton, UK 2011
Copy number variants in epilepsy: Identification of novel susceptibility loci North East Epilepsy Meeting Newcastle Upon Tyne, England 2010
A Spectrum of Genomic Disorders DECIPHER Symposium Hinxton, UK 2010

Research Funding

Grant Title Grantor Amount Award Date
7 of 7 Epi4K: Gene discovery in 4,000 epilepsy genomes NIH/NINDS Sept. 30, 2011 - Sept. 30, 2016
4 of 7 Epi4K: Gene discovery in 4,000 epilepsy genomes NIH/NINDS Sept. 30, 2011 - Sept. 30, 2014
3 of 7 Epi4K: Gene discovery in 4,000 epilepsy genomes NIH/NINDS Sept. 30, 2011 - Sept. 30, 2016
A Genomic Approach to Epilepsy NIH/NINDS $ Feb. 15, 2010 - Jan. 31, 2014
Novel Genomic Rearrangements in Developmental Pediatric Disorders Burroughs Wellcome Fund $ Jan. 18, 2010 - Aug. 31, 2016