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

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

doi:10.1016/s1096-7192(21)00373-5

Cited by 6 publications

(22 citation statements)

References 42 publications

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“…Although we report the treatment of 2 skeletally mature patients with PAO, we acknowledge that this treatment may not be widely available given the complexity of the procedure. However, early diagnosis during the first months of life may allow for nonsurgical treatment with bracing as previously reported 2,5,7 . Once the diagnosis of WDSTS is made, the caring physician should have in mind the possibility of hip dysplasia despite the lack of symptoms.…”

Section: Discussionmentioning

confidence: 71%

“…First described in 1989 by Wiedemann et al, observation was made regarding a White boy with growth deficiency, developmental delay, and physical presentation, including distinct facial features (round and flat face, short nose, hypertelorism, long philtrum, short palpebral fissures, high arch palate, and low-set ears), short and thick limbs, alternating convergent strabismus, and dilatation of the renal calyces (Fig. 1) 1-3 . Since then, further investigation through whole-exome sequencing has identified heterozygous de novo variants in the MLL gene (now known as KMT2A) , resulting in dysregulation in chromatin remodeling 4 .…”

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confidence: 99%

“…Additional case reports and clinical evaluation have expanded our understanding of this disorder to include various orthopaedic manifestations. These include anomalies of the spine (cervical fusion, scoliosis, and tethered cord), rib cage/chest wall (pectus excavatum and hypoplastic, missing, or cervical ribs), digits (broad or tapering fingers, small hands/feet, clinodactyly, and delayed bone age), and hips (developmental hip dysplasia, DDH) 2,5-7 . Hip dysplasia has been variably reported, but its clinical significance remains to be highlighted, particularly from an orthopaedic surgical perspective.…”

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confidence: 99%

“…Sheppard et al performed a retrospective, multicenter, observational study of 104 individuals with WDSTS wherein they reported 5 participants with hip dysplasia, of which 4 required surgery and 1 was treated with Pavlik harness 2 . Ko et al presented 2 patients who had DDH requiring a Pavlik harness 5 .…”

mentioning

confidence: 99%

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Severe Hip Dysplasia in Wiedemann-Steiner Syndrome Treated with Bilateral Bernese Periacetabular Osteotomy

Evans

Novais

2022

JBJS Case Connector

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Case:Wiedemann-Steiner syndrome (WDSTS) is a rare autosomal dominant disorder with many phenotypic characteristics, including multiple orthopaedic manifestations. Of these, symptomatic significant hip dysplasia has been variably noted. Nonetheless, few reports detail surgical treatment for these patients, including hip preservation for those with hip dysplasia.Conclusion:Periacetabular osteotomy allows for the correction of severe hip dysplasia in patients with WDSTS. With proper recognition and timely intervention, adequate care may be provided for these patients.

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Section: Discussionmentioning

confidence: 71%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Severe Hip Dysplasia in Wiedemann-Steiner Syndrome Treated with Bilateral Bernese Periacetabular Osteotomy

Evans

Novais

2022

JBJS Case Connector

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“…31 Hypogammaglobinemia, growth hormone deficiency, craniovertebral junction anomalies, Chiari malformation, tethered cord, and gut dysmotility (constipation) have been reported in few individuals. 31,32…”

Section: Wiedemann-steiner Syndromementioning

confidence: 99%

Disorders of histone methylation: Molecular basis and clinical syndromes

et al. 2022

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Epigenetic modifications of DNA and histone tails are essential for gene expression regulation. They play an essential role in neurodevelopment as nervous system development is a complex process requiring a dynamic pattern of gene expression. Histone methylation is one of the vital epigenetic regulators and mostly occurs on lysine residues of histones H3 and H4. Histone methylation is catalyzed by two sets of enzymes: histone lysine methyltransferases (KMTs) and histone lysine demethylases (KDMs). KMT2 enzymes form a distinct multi-subunit complex known as COMPASS to enhance their catalytic activity and diversify their biologic functions. Several neurodevelopmental syndromes result from defects in histone methylation which can be caused by deficiencies in histone methyltransferases and demethylases, loss of the histone methyltransferase activator TASP1, or derangements in COMPASS formation. In this review article, the molecular mechanism of histone methylation is discussed followed by summarizing clinical syndromes caused by monogenic defects in histone methylation.

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Sleep disturbance is a common feature of Kabuki syndrome

Rapp

Kalinousky

Johnson

et al. 2022

American J of Med Genetics Pt A

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Kabuki syndrome (KS) is a rare epigenetic disorder caused by heterozygous loss of function variants in either KMT2D (90%) or KDM6A (10%), both involved in regulation of histone methylation. While sleep disturbance in other Mendelian disorders of the epigenetic machinery has been reported, no study has been conducted on sleep in KS. This study assessed sleep in 59 participants with KS using a validated sleep questionnaire. Participants ranged in age from 4 to 43 years old with 86% of participants having a pathogenic variant in KMT2D. In addition, data on adaptive function, behavior, anxiety, and quality of life were collected using their respective questionnaires. Some form of sleep issue was present in 71% of participants, with night-waking, daytime sleepiness, and sleep onset delay being the most prevalent. Sleep dysfunction was positively correlated with maladaptive behaviors, anxiety levels, and decreasing quality of life. Sleep issues were not correlated with adaptive function. This study establishes sleep disturbance as a common feature of KS. Quantitative sleep measures may be a useful outcome measure for clinical trials in KS. Further, clinicians caring for those with KS should consider sleep dysfunction as an important feature that impacts overall health and well being in these patients.

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

Cited by 6 publications

References 42 publications

Severe Hip Dysplasia in Wiedemann-Steiner Syndrome Treated with Bilateral Bernese Periacetabular Osteotomy

Severe Hip Dysplasia in Wiedemann-Steiner Syndrome Treated with Bilateral Bernese Periacetabular Osteotomy

Disorders of histone methylation: Molecular basis and clinical syndromes

Sleep disturbance is a common feature of Kabuki syndrome

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