Research Overview

We are studying patients with Angelman syndrome (AS), a developmental disorder that affects movement, speech and social behavior, and investigating interventions that could potentially improve the care of patients with this condition. AS is caused by a deficiency of a maternally-expressed gene and is manifested at birth. Symptoms may include, but are not limited to, functionally severe developmental delay, speech impairments, movement or balance problems, and behavioral uniqueness, including a combination of frequent laughter or smiling, apparent happy demeanor, easily excitable personality, hand flapping movements and short attention span.

Current Projects:

Characterization of Angelman syndrome

We are conducting an observational study, following children with AS over 5 to 10 years to gain a better understanding of disease progression and the clinical features of AS's four molecular subclasses. The study will also attempt to establish genotype-phenotype correlations, which might aid in clinical care of AS patients.

To learn more, please click here.

A trial of levodopa in Angelman syndrome

Levodopa is a drug commonly used in adults with Parkinson disease to control tremors and involuntary movements. Levodopa is not FDA-approved for use in children, but many children have used this drug for a variety of medical conditions over the last 30 years. Parents who put their children with AS on levodopa have reported improvements in cognition and abnormal movements, but the drug has not been rigorously studied in AS. Therefore, the goal of this study is to understand the efficacy of levodopa in these children.

To learn more, please click here.

About Wen-Hann Tan

Wen-Hann Tan is an attending physician at Boston Children's Hospital and an Instructor in Pediatrics at Harvard Medical School. He received his MD from the University of Nottingham Medical School (UK). He completed his internship in internal medicine, surgery and pediatrics at the University Hospital in Nottingham. He completed residencies in general pediatrics at West Suffolk Hospital and Addenbrooke's Hospital (East Anglia, UK), and in pediatrics at Massachusetts General Hospital. He subsequently completed a fellowship in clinical genetics at Harvard Medical School. He is board-certified in clinical genetics and general pediatrics.

Key Publications

  • Gentile JK et al. A neurodevelopmental survey of Angelman syndrome with genotype-phenotype correlations. J Dev Behav Pediatr 2010 Sep; 31(7):592-601.
     
  • Tan WH et al. Angelman syndrome: Mutations influence features in early childood.Am J Med Genet 2010 (accepted).

To see a complete list of Dr. Tan's publications in PubMed, click here.

Researcher Services

Researcher Areas

  • Angelman Syndrome

Research Departments

Research Divisions

PUBLICATIONS

Publications powered by Harvard Catalyst Profiles

  1. Sadhwani A, Sanjana NE, Willen JM, Calculator SN, Black ED, Bean LJH, Li H, Tan WH. Two Angelman families with unusually advanced neurodevelopment carry a start codon variant in the most highly expressed UBE3A isoform. Am J Med Genet A. 2018 May 07. View abstract
  2. Gold NB, Blumenthal JA, Wessel AE, Stein DR, Scott A, Fox VL, Turner A, Kritzer A, Rajabi F, Peeler K, Tan WH. Acute Pancreatitis in a Patient with Maple Syrup Urine Disease: A Management Paradox. J Pediatr. 2018 Apr 19. View abstract
  3. Tan WH, Bird LM, Sadhwani A, Barbieri-Welge RL, Skinner SA, Horowitz LT, Bacino CA, Noll LM, Fu C, Hundley RJ, Wink LK, Erickson CA, Barnes GN, Slavotinek A, Jeremy R, Rotenberg A, Kothare SV, Olson HE, Poduri A, Nespeca MP, Chu HC, Willen JM, Haas KF, Weeber EJ, Rufo PA. A randomized controlled trial of levodopa in patients with Angelman syndrome. Am J Med Genet A. 2018 May; 176(5):1099-1107. View abstract
  4. Rajabi F, Rodan LH, Jonas MM, Soul JS, Ullrich NJ, Wessel A, Waisbren SE, Tan WH, Berry GT. Liver Failure as the Presentation of Ornithine Transcarbamylase Deficiency in a 13-Month-Old Female. JIMD Rep. 2017 Sep 09. View abstract
  5. Dy ME, Chang FC, Jesus SD, Anselm I, Mahant N, Zeilman P, Rodan LH, Foote KD, Tan WH, Eskandar E, Sharma N, Okun MS, Fung VS, Waugh JL. Treatment of ADCY5-Associated Dystonia, Chorea, and Hyperkinetic Disorders With Deep Brain Stimulation: A Multicenter Case Series. J Child Neurol. 2016 07; 31(8):1027-35. View abstract
  6. Tan WH, Bird LM. Pharmacological therapies for Angelman syndrome. Wien Med Wochenschr. 2017 Jun; 167(9-10):205-218. View abstract
  7. Brownstein CA, Beggs AH, Rodan L, Shi J, Towne MC, Pelletier R, Cao S, Rosenberg PA, Urion DK, Picker J, Tan WH, Agrawal PB. Clinical heterogeneity associated with KCNA1 mutations include cataplexy and nonataxic presentations. Neurogenetics. 2016 Jan; 17(1):11-6. View abstract
  8. Russell B, Johnston JJ, Biesecker LG, Kramer N, Pickart A, Rhead W, Tan WH, Brownstein CA, Kate Clarkson L, Dobson A, Rosenberg AZ, Vergano SA, Helm BM, Harrison RE, Graham JM. Clinical management of patients with ASXL1 mutations and Bohring-Opitz syndrome, emphasizing the need for Wilms tumor surveillance. Am J Med Genet A. 2015 Sep; 167A(9):2122-31. View abstract
  9. Nakayama T, Al-Maawali A, El-Quessny M, Rajab A, Khalil S, Stoler JM, Tan WH, Nasir R, Schmitz-Abe K, Hill RS, Partlow JN, Al-Saffar M, Servattalab S, LaCoursiere CM, Tambunan DE, Coulter ME, Elhosary PC, Gorski G, Barkovich AJ, Markianos K, Poduri A, Mochida GH. Mutations in PYCR2, Encoding Pyrroline-5-Carboxylate Reductase 2, Cause Microcephaly and Hypomyelination. Am J Hum Genet. 2015 May 07; 96(5):709-19. View abstract
  10. Tan WH. Commentary. Clin Chem. 2015 Jan; 61(1):54. View abstract
  11. Smpokou P, Fox VL, Tan WH. PTEN hamartoma tumour syndrome: early tumour development in children. Arch Dis Child. 2015 Jan; 100(1):34-7. View abstract
  12. Olson H, Shen Y, Avallone J, Sheidley BR, Pinsky R, Bergin AM, Berry GT, Duffy FH, Eksioglu Y, Harris DJ, Hisama FM, Ho E, Irons M, Jacobsen CM, James P, Kothare S, Khwaja O, Lipton J, Loddenkemper T, Markowitz J, Maski K, Megerian JT, Neilan E, Raffalli PC, Robbins M, Roberts A, Roe E, Rollins C, Sahin M, Sarco D, Schonwald A, Smith SE, Soul J, Stoler JM, Takeoka M, Tan WH, Torres AR, Tsai P, Urion DK, Weissman L, Wolff R, Wu BL, Miller DT, Poduri A. Copy number variation plays an important role in clinical epilepsy. Ann Neurol. 2014 Jun; 75(6):943-58. View abstract
  13. Tan WH, Bird LM, Thibert RL, Williams CA. If not Angelman, what is it? A review of Angelman-like syndromes. Am J Med Genet A. 2014 Apr; 164A(4):975-92. View abstract
  14. von Oettingen JE, Tan WH, Dauber A. Skeletal dysplasia, global developmental delay, and multiple congenital anomalies in a 5-year-old boy-report of the second family with B3GAT3 mutation and expansion of the phenotype. Am J Med Genet A. 2014 Jun; 164A(6):1580-6. View abstract
  15. Hodge JC, Mitchell E, Pillalamarri V, Toler TL, Bartel F, Kearney HM, Zou YS, Tan WH, Hanscom C, Kirmani S, Hanson RR, Skinner SA, Rogers RC, Everman DB, Boyd E, Tapp C, Mullegama SV, Keelean-Fuller D, Powell CM, Elsea SH, Morton CC, Gusella JF, DuPont B, Chaubey A, Lin AE, Talkowski ME. Disruption of MBD5 contributes to a spectrum of psychopathology and neurodevelopmental abnormalities. Mol Psychiatry. 2014 Mar; 19(3):368-79. View abstract
  16. Tan WH, Gilmore EC, Baris HN. In: Rimoin DL, Pyeritz RE, Korf BR, editors. Emery and Rimoin's Principles and Practice of Medical Genetics. Human Developmental Genetics. 2013. View abstract
  17. Mochida GH, Ganesh VS, de Michelena MI, Dias H, Atabay KD, Kathrein KL, Huang HT, Hill RS, Felie JM, Rakiec D, Gleason D, Hill AD, Malik AN, Barry BJ, Partlow JN, Tan WH, Glader LJ, Barkovich AJ, Dobyns WB, Zon LI, Walsh CA. CHMP1A encodes an essential regulator of BMI1-INK4A in cerebellar development. Nat Genet. 2012 Nov; 44(11):1260-4. View abstract
  18. Bower M, Salomon R, Allanson J, Antignac C, Benedicenti F, Benetti E, Binenbaum G, Jensen UB, Cochat P, DeCramer S, Dixon J, Drouin R, Falk MJ, Feret H, Gise R, Hunter A, Johnson K, Kumar R, Lavocat MP, Martin L, Morinière V, Mowat D, Murer L, Nguyen HT, Peretz-Amit G, Pierce E, Place E, Rodig N, Salerno A, Sastry S, Sato T, Sayer JA, Schaafsma GC, Shoemaker L, Stockton DW, Tan WH, Tenconi R, Vanhille P, Vats A, Wang X, Warman B, Weleber RG, White SM, Wilson-Brackett C, Zand DJ, Eccles M, Schimmenti LA, Heidet L. Update of PAX2 mutations in renal coloboma syndrome and establishment of a locus-specific database. Hum Mutat. 2012 Mar; 33(3):457-66. View abstract
  19. Takano K, Tan WH, Irons MB, Jones JR, Schwartz CE. Pitt-Hopkins syndrome should be in the differential diagnosis for males presenting with an ATR-X phenotype. Clin Genet. 2011 Dec; 80(6):600-1. View abstract
  20. Bird LM, Tan WH, Bacino CA, Peters SU, Skinner SA, Anselm I, Barbieri-Welge R, Bauer-Carlin A, Gentile JK, Glaze DG, Horowitz LT, Mohan KN, Nespeca MP, Sahoo T, Sarco D, Waisbren SE, Beaudet AL. A therapeutic trial of pro-methylation dietary supplements in Angelman syndrome. Am J Med Genet A. 2011 Dec; 155A(12):2956-63. View abstract
  21. Tan WH, Bacino CA, Skinner SA, Anselm I, Barbieri-Welge R, Bauer-Carlin A, Beaudet AL, Bichell TJ, Gentile JK, Glaze DG, Horowitz LT, Kothare SV, Lee HS, Nespeca MP, Peters SU, Sahoo T, Sarco D, Waisbren SE, Bird LM. Angelman syndrome: Mutations influence features in early childhood. Am J Med Genet A. 2011 Jan; 155A(1):81-90. View abstract
  22. Mochida GH, Ganesh VS, Felie JM, Gleason D, Hill RS, Clapham KR, Rakiec D, Tan WH, Akawi N, Al-Saffar M, Partlow JN, Tinschert S, Barkovich AJ, Ali B, Al-Gazali L, Walsh CA. A homozygous mutation in the tight-junction protein JAM3 causes hemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts. Am J Hum Genet. 2010 Dec 10; 87(6):882-9. View abstract
  23. Gentile JK, Tan WH, Horowitz LT, Bacino CA, Skinner SA, Barbieri-Welge R, Bauer-Carlin A, Beaudet AL, Bichell TJ, Lee HS, Sahoo T, Waisbren SE, Bird LM, Peters SU. A neurodevelopmental survey of Angelman syndrome with genotype-phenotype correlations. J Dev Behav Pediatr. 2010 Sep; 31(7):592-601. View abstract
  24. Vendrame M, Maski KP, Chatterjee M, Heshmati A, Krishnamoorthy K, Tan WH, Kothare SV. Epilepsy in Prader-Willi syndrome: clinical characteristics and correlation to genotype. Epilepsy Behav. 2010 Nov; 19(3):306-10. View abstract
  25. Ching MS, Shen Y, Tan WH, Jeste SS, Morrow EM, Chen X, Mukaddes NM, Yoo SY, Hanson E, Hundley R, Austin C, Becker RE, Berry GT, Driscoll K, Engle EC, Friedman S, Gusella JF, Hisama FM, Irons MB, Lafiosca T, LeClair E, Miller DT, Neessen M, Picker JD, Rappaport L, Rooney CM, Sarco DP, Stoler JM, Walsh CA, Wolff RR, Zhang T, Nasir RH, Wu BL. Deletions of NRXN1 (neurexin-1) predispose to a wide spectrum of developmental disorders. Am J Med Genet B Neuropsychiatr Genet. 2010 Jun 05; 153B(4):937-47. View abstract
  26. Manzini MC, Rajab A, Maynard TM, Mochida GH, Tan WH, Nasir R, Hill RS, Gleason D, Al Saffar M, Partlow JN, Barry BJ, Vernon M, LaMantia AS, Walsh CA. Developmental and degenerative features in a complicated spastic paraplegia. Ann Neurol. 2010 Apr; 67(4):516-25. View abstract
  27. Miller DT, Shen Y, Weiss LA, Korn J, Anselm I, Bridgemohan C, Cox GF, Dickinson H, Gentile J, Harris DJ, Hegde V, Hundley R, Khwaja O, Kothare S, Luedke C, Nasir R, Poduri A, Prasad K, Raffalli P, Reinhard A, Smith SE, Sobeih MM, Soul JS, Stoler J, Takeoka M, Tan WH, Thakuria J, Wolff R, Yusupov R, Gusella JF, Daly MJ, Wu BL. Microdeletion/duplication at 15q13.2q13.3 among individuals with features of autism and other neuropsychiatric disorders. J Med Genet. 2009 Apr; 46(4):242-8. View abstract
  28. Baris HN, Tan WH, Kimonis VE, Irons MB. Diagnostic utility of array-based comparative genomic hybridization in a clinical setting. Am J Med Genet A. 2007 Nov 01; 143A(21):2523-33. View abstract
  29. Tan WH, Baris HN, Burrows PE, Robson CD, Alomari AI, Mulliken JB, Fishman SJ, Irons MB. The spectrum of vascular anomalies in patients with PTEN mutations: implications for diagnosis and management. J Med Genet. 2007 Sep; 44(9):594-602. View abstract
  30. Eichler F, Tan WH, Shih VE, Grant PE, Krishnamoorthy K. Proton magnetic resonance spectroscopy and diffusion-weighted imaging in isolated sulfite oxidase deficiency. J Child Neurol. 2006 Sep; 21(9):801-5. View abstract
  31. Baris H, Bejjani BA, Tan WH, Coulter DL, Martin JA, Storm AL, Burton BK, Saitta SC, Gajecka M, Ballif BC, Irons MB, Shaffer LG, Kimonis VE. Identification of a novel polymorphism--the duplication of the NPHP1 (nephronophthisis 1) gene. Am J Med Genet A. 2006 Sep 01; 140A(17):1876-9. View abstract
  32. Tan WH, Eichler FS, Hoda S, Lee MS, Baris H, Hanley CA, Grant PE, Krishnamoorthy KS, Shih VE. Isolated sulfite oxidase deficiency: a case report with a novel mutation and review of the literature. Pediatrics. 2005 Sep; 116(3):757-66. View abstract
  33. Baris H, Legum C, Levin L, Magal N, Drasinover V, Tan WH, Halpern GJ, Shohat T, Shohat M. A putative new locus for an autosomal recessive cerebellar ataxia syndrome on chromosome 22q11. Clin Genet. 2005 Aug; 68(2):185-7. View abstract
  34. Tan WH, Baris H, Robson CD, Kimonis VE. Cockayne syndrome: the developing phenotype. Am J Med Genet A. 2005 Jun 01; 135(2):214-6. View abstract
  35. Baris H, Tan WH, Kimonis VE. Hypothelia, syndactyly, and ear malformation--a variant of the scalp-ear-nipple syndrome?: Case report and review of the literature. Am J Med Genet A. 2005 Apr 15; 134A(2):220-2. View abstract
  36. Tan WH, Brown N, Kelsall AW, McClure RJ. Dose regimen for vancomycin not needing serum peak levels? Arch Dis Child Fetal Neonatal Ed. 2002 Nov; 87(3):F214-6. View abstract