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.

Angelman syndrome clinical research studies

Gene identification for rare Mendelian disorders in collaboration with various basic science laboratories Clinical trials in rare Mendelian disorders

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Dr. Tan is a clinical geneticist with an interest in a broad range of rare and ultra-rare Mendelian disorders, including pediatric cancer predisposition syndromes. He is also interested in the design of clinical trials for rare genetic syndromes. After graduating from medical school in Nottingham (United Kingdom), he undertook training in pediatrics and clinical genetics in Nottingham, Bury St. Edmunds, Cambridge (Cambridgeshire), and Boston. He has been on the faculty at Boston Children’s Hospital since 2006 and has been actively involved in clinical research studies on Angelman syndrome since then. He leads the Boston site of the Angelman Syndrome Natural History study and was the overall principal investigator of a multi-center phase II/III clinical trial of levodopa in Angelman syndrome.

He is also interested in Bohring-Opitz syndrome and serves on the Medical Advisory Board of the Bohring- Opitz Syndrome Foundation.

In addition, he now serves as the site PI of a gene therapy trial in adults with ornithine transcarbamylase deficiency.

Selected Publications

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; 155A(1):81-90.

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; 155A(12):2956-63.

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; 164A(4):975- 92.

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; 164A(6):1580-6.

Smpokou P, Fox VL, Tan WH. PTEN hamartoma tumour syndrome: early tumour development in children. Arch Dis Child. 2015; 100(1):34-7.

Tan WH, Bird LM. Angelman syndrome: Current and emerging therapies in 2016. Am J Med Genet C Semin Med Genet. 2016 Nov 8. doi: 10.1002/ajmg.c.31536. [Epub ahead of print]

Bird LM, Tan WH. Treatment of genetic disorders-A vision coming into focus. Am J Med Genet C Semin Med Genet. 2016 Nov 3. doi: 10.1002/ajmg.c.31535. [Epub ahead of print]

Lamont RE, Tan WH, Innes AM, Parboosingh JS, Schneidman-Duhovny D, Rajkovic A, Pappas J, Altschwager P, DeWard S, Fulton A, Gray KJ, Krall M, Mehta L, Rodan LH, Saller DN Jr, Steele D, Stein D, Yatsenko SA, Bernier FP, Slavotinek AM. Expansion of phenotype and genotypic data in CRB2-related syndrome. Eur J Hum Genet. 2016 Oct;24(10):1436-44.


Publications powered by Harvard Catalyst Profiles

  1. Proposed criteria for nevoid basal cell carcinoma syndrome in children assessed using statistical optimization. Sci Rep. 2021 Oct 05; 11(1):19791. View abstract
  2. The Unrecognized Mortality Burden of Genetic Disorders in Infancy. Am J Public Health. 2021 07; 111(S2):S156-S162. View abstract
  3. Developmental Skills of Individuals with Angelman Syndrome Assessed Using the Bayley-III. J Autism Dev Disord. 2021 Jan 30. View abstract
  4. The STARS Phase 2 Study: A Randomized Controlled Trial of Gaboxadol in Angelman Syndrome. Neurology. 2021 02 16; 96(7):e1024-e1035. View abstract
  5. Exome sequencing identifies novel missense and deletion variants in RTN4IP1 associated with optic atrophy, global developmental delay, epilepsy, ataxia, and choreoathetosis. Am J Med Genet A. 2021 01; 185(1):203-207. View abstract
  6. Cleft Lip and Palate in Ectodermal Dysplasia. Cleft Palate Craniofac J. 2021 02; 58(2):237-243. View abstract
  7. Genetic diagnoses and associated anomalies in fetuses prenatally diagnosed with esophageal atresia. Am J Med Genet A. 2020 08; 182(8):1890-1895. View abstract
  8. Infant mortality: the contribution of genetic disorders. J Perinatol. 2019 12; 39(12):1611-1619. View abstract
  9. Genome Sequencing Identifies the Pathogenic Variant Missed by Prior Testing in an Infant with Marfan Syndrome. J Pediatr. 2019 10; 213:235-240. View abstract
  10. Maladaptive behaviors in individuals with Angelman syndrome. Am J Med Genet A. 2019 06; 179(6):983-992. View abstract
  11. Prenatal imaging throughout gestation in Beckwith-Wiedemann syndrome. Prenat Diagn. 2019 08; 39(9):792-795. View abstract
  12. Two Angelman families with unusually advanced neurodevelopment carry a start codon variant in the most highly expressed UBE3A isoform. . 2018 07; 176(7):1641-1647. View abstract
  13. Acute Pancreatitis in a Patient with Maple Syrup Urine Disease: A Management Paradox. J Pediatr. 2018 07; 198:313-316. View abstract
  14. A randomized controlled trial of levodopa in patients with Angelman syndrome. Am J Med Genet A. 2018 05; 176(5):1099-1107. View abstract
  15. Liver Failure as the Presentation of Ornithine Transcarbamylase Deficiency in a 13-Month-Old Female. JIMD Rep. 2018; 40:17-22. View abstract
  16. 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
  17. Pharmacological therapies for Angelman syndrome. Wien Med Wochenschr. 2017 Jun; 167(9-10):205-218. View abstract
  18. Clinical heterogeneity associated with KCNA1 mutations include cataplexy and nonataxic presentations. Neurogenetics. 2016 Jan; 17(1):11-6. View abstract
  19. Clinical management of patients with ASXL1 mutations and Bohring-Opitz syndrome, emphasizing the need for Wilms tumor surveillance. . 2015 Sep; 167A(9):2122-31. View abstract
  20. 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
  21. Commentary. Clin Chem. 2015 Jan; 61(1):54. View abstract
  22. PTEN hamartoma tumour syndrome: early tumour development in children. Arch Dis Child. 2015 Jan; 100(1):34-7. View abstract
  23. Copy number variation plays an important role in clinical epilepsy. Ann Neurol. 2014 Jun; 75(6):943-58. View abstract
  24. If not Angelman, what is it? A review of Angelman-like syndromes. . 2014 Apr; 164A(4):975-92. View abstract
  25. 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
  26. Disruption of MBD5 contributes to a spectrum of psychopathology and neurodevelopmental abnormalities. Mol Psychiatry. 2014 Mar; 19(3):368-79. View abstract
  27. In: Rimoin DL, Pyeritz RE, Korf BR, editors. Emery and Rimoin's Principles and Practice of Medical Genetics. Human Developmental Genetics. 2013. View abstract
  28. CHMP1A encodes an essential regulator of BMI1-INK4A in cerebellar development. Nat Genet. 2012 Nov; 44(11):1260-4. View abstract
  29. 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
  30. 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
  31. A therapeutic trial of pro-methylation dietary supplements in Angelman syndrome. Am J Med Genet A. 2011 Dec; 155A(12):2956-63. View abstract
  32. Angelman syndrome: Mutations influence features in early childhood. Am J Med Genet A. 2011 Jan; 155A(1):81-90. View abstract
  33. 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
  34. A neurodevelopmental survey of Angelman syndrome with genotype-phenotype correlations. J Dev Behav Pediatr. 2010 Sep; 31(7):592-601. View abstract
  35. Epilepsy in Prader-Willi syndrome: clinical characteristics and correlation to genotype. Epilepsy Behav. 2010 Nov; 19(3):306-10. View abstract
  36. 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
  37. Developmental and degenerative features in a complicated spastic paraplegia. Ann Neurol. 2010 Apr; 67(4):516-25. View abstract
  38. 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
  39. Diagnostic utility of array-based comparative genomic hybridization in a clinical setting. . 2007 Nov 01; 143A(21):2523-33. View abstract
  40. 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
  41. Proton magnetic resonance spectroscopy and diffusion-weighted imaging in isolated sulfite oxidase deficiency. J Child Neurol. 2006 Sep; 21(9):801-5. View abstract
  42. Identification of a novel polymorphism--the duplication of the NPHP1 (nephronophthisis 1) gene. . 2006 Sep 01; 140A(17):1876-9. View abstract
  43. 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
  44. A putative new locus for an autosomal recessive cerebellar ataxia syndrome on chromosome 22q11. Clin Genet. 2005 Aug; 68(2):185-7. View abstract
  45. Cockayne syndrome: the developing phenotype. . 2005 Jun 01; 135(2):214-6. View abstract
  46. Hypothelia, syndactyly, and ear malformation--a variant of the scalp-ear-nipple syndrome?: Case report and review of the literature. . 2005 Apr 15; 134A(2):220-2. View abstract
  47. Dose regimen for vancomycin not needing serum peak levels? Arch Dis Child Fetal Neonatal Ed. 2002 Nov; 87(3):F214-6. View abstract