TITLE

De Novo variants in the KMT2A (MLL) gene causing atypical Wiedemann-Steiner syndrome in two unrelated individuals identified by clinical exome sequencing

AUTHOR(S)
Strom, Samuel P.; Lozano, Reymundo; Hane Lee; Naghmeh Dorrani; Mann, John; O'Lague, Patricia F.; Mans, Nicole; Deignan, Joshua L.; Vilain, Eric; Nelson, Stanley F.; Grody, Wayne W.; Quintero-Rivera, Fabiola
PUB. DATE
May 2014
SOURCE
BMC Medical Genetics;2014, Vol. 15 Issue 1, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background Wiedemann-Steiner Syndrome (WSS) is characterized by short stature, a variety of dysmorphic facial and skeletal features, characteristic hypertrichosis cubiti (excessive hair on the elbows), mild-to-moderate developmental delay and intellectual disability. [MIM#: 605130]. Here we report two unrelated children for whom clinical exome sequencing of parent-proband trios was performed at UCLA, resulting in a molecular diagnosis of WSS and atypical clinical presentation. Case presentation For patient 1, clinical features at 9 years of age included developmental delay, craniofacial abnormalities, and multiple minor anomalies. Patient 2 presented at 1 year of age with developmental delay, microphthalmia, partial 3-4 left hand syndactyly, and craniofacial abnormalities. A de novo missense c.4342T>C variant and a de novo splice site c.4086+G>A variant were identified in the KMT2A gene in patients 1 and 2, respectively. Conclusions Based on the clinical and molecular findings, both patients appear to have novel presentations of WSS. As the hallmark hypertrichosis cubiti was not initially appreciated in either case, this syndrome was not suspected during the clinical evaluation. This report expands the phenotypic spectrum of the clinical phenotypes and KMT2A variants associated with WSS.
ACCESSION #
96050071

 

Related Articles

  • Child with Deletion 9p Syndrome Presenting with Craniofacial Dysmorphism, Developmental Delay, and Multiple Congenital Malformations. Sirisena, Nirmala D.; Wijetunge, U. Kalpani S.; de Silva, Ramya; Dissanayake, Vajira H. W. // Case Reports in Genetics;2013, p1 

    A 4-month-old Sri Lankanmale child case with a de novo terminal deletion in the p22→pter region of chromosome 9 is described. The child presented with craniofacial dysmorphism, developmental delay, and congenital malformations in agreement with the consensus phenotype. A distinctive...

  • Two Indian families with Greig cephalopolysyndactyly with non-syndromic phenotype. Sethi, Sidharth; Goyal, Deepak; Khalil, Sumaira; Yadav, Dinesh // European Journal of Pediatrics;Aug2013, Vol. 172 Issue 8, p1131 

    The Greig cephalopolysyndactyly syndrome (GCPS) is a rare, autosomal dominant, pleiotropic, multiple congenital anomaly syndrome. The typical findings include hypertelorism, macrocephaly with frontal bossing, and polysyndactyly. We present two families, with GCPS with a non-syndromic phenotype,...

  • Operative Management of OSAS in a Complex Case of Proteus Syndrome. Cantone, Elena; Cavaliere, Michele; Castagna, Giovanni; Marino, Anna; Del Vecchio, Luigi; Iengo, Maurizio // Case Reports in Otolaryngology;6/23/2015, Vol. 2015, p1 

    Obstructive sleep apnea syndrome (OSAS) is a common disorder in childhood with high prevalence in syndromic subjects with craniofacial malformations. Proteus Syndrome (PS) is a rare hamartoneoplastic disorder associated with disproportionate and asymmetric overgrowth of body parts and...

  • Multiple Dental and Skeletal Abnormalities in an Individual with Filippi Syndrome. Sandhu, Meera; Malik, Pooja; Saha, Rooposhi // Case Reports in Dentistry;2013, p1 

    Filippi syndrome is an autosomal recessive condition characterized by variable soft tissue syndactyly of the fingers and toes, microcephaly, pre- and postnatal growth retardation, mildly abnormal craniofacial appearance, and mental retardation. We report on a child with Filippi syndrome who...

  • Deletions involving genes WHSC1 and LETM1 may be necessary, but are not sufficient to cause Wolf-Hirschhorn Syndrome. Andersen, Erica F; Carey, John C; Earl, Dawn L; Corzo, Deyanira; Suttie, Michael; Hammond, Peter; South, Sarah T // European Journal of Human Genetics;Apr2014, Vol. 22 Issue 4, p464 

    Wolf-Hirschhorn syndrome (WHS) is a complex genetic disorder caused by the loss of genomic material from the short arm of chromosome 4. Genotype-phenotype correlation studies indicated that the loss of genes within 4p16.3 is necessary for expression of the core features of the phenotype. Within...

  • Another Rare Case of a Child with de novo Terminal 9p Deletion and Co-Existing Interstitial 9p Duplication: Clinical Findings and Molecular Cytogenetic Study by Array-CGH. Kowalczyk, M.; Tomaszewska, a.; Podbioł-Palenta, a.; Constantinou, M.; Wawrzkiewicz-Witkowska, a.; Kowalski, J.; Kałużewski, B.; Zajączek, S.; Srebniak, M.I. // Cytogenetic & Genome Research;2012, Vol. 139 Issue 1, p9 

    Trisomy 9p is the fourth most common chromosome abnormality found in liveborns. We report on a rare case of partial trisomy 9p complicated by partial monosomy 9p. Clinical manifestation included craniofacial abnormalities typical for trisomy 9p syndrome, developmental delay, mental retardation...

  • Further Magnetic Resonance Imaging (MRI) Brain Delineation of 49,XXXXY Syndrome. Tabarki, Brahim; Shafi, Shatha Al; Adwani, Nawal Al; Shahwan, Saad Al // Journal of Child Neurology;May2012, Vol. 27 Issue 5, p650 

    A rare sex chromosome aneuploidy syndrome, 49,XXXXY syndrome is characterized by mental retardation with severe learning difficulties, craniofacial and skeletal abnormalities, hypogonadism, and congenital heart disease. The authors describe a 30-month-old boy with 49,XXXXY syndrome, global...

  • Cornelia de lange syndrome. Tayebi, Naeimeh // Indian Journal of Human Genetics;Jan-Apr2008, Vol. 14 Issue 1, p23 

    BACKGROUND: Cornelia de Lange syndrome (CDLS) is a rare multiple congenital anomaly syndrome characterized by a distinctive facial appearance, developmental delay, growth retardation, low birth weight, skeletal formation anomaly, and hirsutism. CASE: Here for the first time a case of CDLS from...

  • Autosomal Recessive Oculodentodigital Dysplasia: A Case Report and Review of the Literature. Taşdelen, Elifcan; Durmaz, Ceren D.; Karabulut, Halil G. // Cytogenetic & Genome Research;Jul2018, Vol. 154 Issue 4, p181 

    Oculodentodigital dysplasia (ODDD) is a rare condition characterized by a typical facial appearance and variable findings of the eyes, teeth, and fingers. ODDD is caused by mutations in the GJA1 gene in chromosome 6q22 and inherited in an autosomal dominant manner in the majority of the...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics