| Literature DB >> 33783954 |
Sarah E Sheppard1,2, Ian M Campbell1,2, Margaret H Harr1, Nina Gold3, Dong Li1, Hans T Bjornsson4,5,6, Julie S Cohen7,8, Jill A Fahrner4,9, Ali Fatemi7,10, Jacqueline R Harris7,8, Catherine Nowak11, Cathy A Stevens12, Katheryn Grand13, Margaret Au13, John M Graham13, Pedro A Sanchez-Lara13, Miguel Del Campo14, Marilyn C Jones14, Omar Abdul-Rahman15, Fowzan S Alkuraya16, Jennifer A Bassetti17, Katherine Bergstrom17, Elizabeth Bhoj1,2,18, Sarah Dugan19, Julie D Kaplan15, Nada Derar20, Karen W Gripp21, Natalie Hauser22, A Micheil Innes23,24, Beth Keena2, Neslida Kodra22, Rebecca Miller22, Beverly Nelson25, Malgorzata J Nowaczyk26, Zuhair Rahbeeni20, Shay Ben-Shachar27, Joseph T Shieh28, Anne Slavotinek28, Andrew K Sobering29, Mary-Alice Abbott30, Dawn C Allain31, Louise Amlie-Wolf21, Ping Yee Billie Au23,24, Emma Bedoukian2, Geoffrey Beek32, James Barry33,34, Janet Berg33,34, Jonathan A Bernstein35, Cheryl Cytrynbaum36, Brian Hon-Yin Chung37, Sarah Donoghue2, Naghmeh Dorrani38,39, Alison Eaton40, Josue A Flores-Daboub19, Holly Dubbs41, Carolyn A Felix42, Chin-To Fong43, Jasmine Lee Fong Fung37, Balram Gangaram28, Amy Goldstein2, Rotem Greenberg27, Thoa K Ha28, Joseph Hersh44, Kosuke Izumi2, Staci Kallish45, Elijah Kravets35, Pui-Yan Kwok28, Rebekah K Jobling36, Amy E Knight Johnson46, Jessica Kushner47, Bo Hoon Lee48, Brooke Levin49, Kristin Lindstrom50, Kandamurugu Manickam31, Rebecca Mardach14, Elizabeth McCormick2, D Ross McLeod23, Frank D Mentch1, Kelly Minks48, Colleen Muraresku2, Stanley F Nelson39,51, Patrizia Porazzi52, Pavel N Pichurin53, Nina N Powell-Hamilton21, Zoe Powis54, Alyssa Ritter2, Caleb Rogers47, Luis Rohena33,34, Carey Ronspies15, Audrey Schroeder43, Zornitza Stark55,56, Lois Starr15, Joan Stoler57, Pim Suwannarat58, Milen Velinov59, Rosanna Weksberg36, Yael Wilnai60, Neda Zadeh61, Dina J Zand62, Marni J Falk2,18, Hakon Hakonarson1,2,18, Elaine H Zackai2,18, Fabiola Quintero-Rivera37,63.
Abstract
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.Entities:
Keywords: KMT2A; MLL1; Wiedemann-Steiner syndrome; hypertrichosis; syndromic intellectual disability; syndromic short stature
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Year: 2021 PMID： 33783954 PMCID： PMC8631250 DOI： 10.1002/ajmg.a.62124
Source DB: PubMed Journal: Am J Med Genet A ISSN： 1552-4825 Impact factor: 2.578