Expanding the genotypic and phenotypic spectrum in a diverse cohort of 104 individuals with Wiedemann-Steiner syndrome

Sarah E. Sheppard, Ian M. Campbell, Margaret H. Harr, Nina Gold, Dong Li, Hans T. Bjornsson, Julie S. Cohen, Jill A. Fahrner, Ali Fatemi, Jacqueline R. Harris, Catherine Nowak, Cathy A. Stevens, Katheryn Grand, Margaret Au, John M. Graham, Pedro A. Sanchez-Lara, Miguel Del Campo, Marilyn C. Jones, Omar Abdul-Rahman, Fowzan S. AlkurayaJennifer A. Bassetti, Katherine Bergstrom, Elizabeth Bhoj, Sarah Dugan, Julie D. Kaplan, Nada Derar, Karen W. Gripp, Natalie Hauser, A. Micheil Innes, Beth Keena, Neslida Kodra, Rebecca Miller, Beverly Nelson, Malgorzata J. Nowaczyk, Zuhair Rahbeeni, Shay Ben-Shachar, Joseph T. Shieh, Anne Slavotinek, Andrew K. Sobering, Mary Alice Abbott, Dawn C. Allain, Louise Amlie-Wolf, Ping Yee Billie Au, Emma Bedoukian, Geoffrey Beek, James Barry, Janet Berg, Jonathan A. Bernstein, Cheryl Cytrynbaum, Brian Hon Yin Chung, Sarah Donoghue, Naghmeh Dorrani, Alison Eaton, Josue A. Flores-Daboub, Holly Dubbs, Carolyn A. Felix, Chin To Fong, Jasmine Lee Fong Fung, Balram Gangaram, Amy Goldstein, Rotem Greenberg, Thoa K. Ha, Joseph Hersh, Kosuke Izumi, Staci Kallish, Elijah Kravets, Pui Yan Kwok, Rebekah K. Jobling, Amy E. Knight Johnson, Jessica Kushner, Bo Hoon Lee, Brooke Levin, Kristin Lindstrom, Kandamurugu Manickam, Rebecca Mardach, Elizabeth McCormick, D. Ross McLeod, Frank D. Mentch, Kelly Minks, Colleen Muraresku, Stanley F. Nelson, Patrizia Porazzi, Pavel N. Pichurin, Nina N. Powell-Hamilton, Zoe Powis, Alyssa Ritter, Caleb Rogers, Luis Rohena, Carey Ronspies, Audrey Schroeder, Zornitza Stark, Lois Starr, Joan Stoler, Pim Suwannarat, Milen Velinov, Rosanna Weksberg, Yael Wilnai, Neda Zadeh, Dina J. Zand, Marni J. Falk, Hakon Hakonarson, Elaine H. Zackai, Fabiola Quintero-Rivera

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


Wiedemann-Steiner syndrome (WSS) is an autosomal dominant disorder caused by monoallelic variants in KMT2A and characterized by intellectual disability and hypertrichosis. We performed a retrospective, multicenter, observational study of 104 individuals with WSS from five continents to characterize the clinical and molecular spectrum of WSS in diverse populations, to identify physical features that may be more prevalent in White versus Black Indigenous People of Color individuals, to delineate genotype–phenotype correlations, to define developmental milestones, to describe the syndrome through adulthood, and to examine clinicians' differential diagnoses. Sixty-nine of the 82 variants (84%) observed in the study were not previously reported in the literature. Common clinical features identified in the cohort included: developmental delay or intellectual disability (97%), constipation (63.8%), failure to thrive (67.7%), feeding difficulties (66.3%), hypertrichosis cubiti (57%), short stature (57.8%), and vertebral anomalies (46.9%). The median ages at walking and first words were 20 months and 18 months, respectively. Hypotonia was associated with loss of function (LoF) variants, and seizures were associated with non-LoF variants. This study identifies genotype–phenotype correlations as well as race-facial feature associations in an ethnically diverse cohort, and accurately defines developmental trajectories, medical comorbidities, and long-term outcomes in individuals with WSS.

Original languageEnglish (US)
Pages (from-to)1649-1665
Number of pages17
JournalAmerican Journal of Medical Genetics, Part A
Issue number6
StatePublished - Jun 2021


  • KMT2A
  • MLL1
  • Wiedemann-Steiner syndrome
  • hypertrichosis
  • syndromic intellectual disability
  • syndromic short stature

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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