Infrequent Manifestations of Kabuki Syndrome in a Patient with Novel <b><i>MLL2</i></b> Mutation

Abstract

We present a case of a 9-month-old Hispanic female with Kabuki syndrome with some infrequent manifestations including a single umbilical artery, butterfly vertebrae, a small larynx, a preauricular pit, microtia with internal ear abnormalities, abnormal calcium metabolism, premature thelarche, neonatal/persistent hypoglycemia and eventration of the diaphragm. She was found to have a previously unreported nonsense MLL2 mutation. This is the first case that includes all such findings occurring simultaneously that was genotyped.

Mutation Update for Kabuki Syndrome GenesKMT2DandKDM6Aand Further Delineation of X-Linked Kabuki Syndrome Subtype 2

“…We searched the HGMD database for mutations in KMT2D and KDM6A and, additionally, conducted a search for further mutations described in original articles in PubMed using the terms "Kabuki syndrome", "MLL2 mutation", and "KMT2D mutation" in different combinations. We examined the clinical and molecular information available from the retrieved 21 mutation screening studies [Ng et al, 2010;Hannibal et al, 2011;Li et al, 2011;Micale et al, 2011;Paulussen et al, 2011;Banka et al, 2012;Courcet et al, 2013;Lindgren et al, 2013;Makrythanasis et al, 2013;Miyake et al, 2013aMiyake et al, , 2013bCheon et al, 2014;Micale et al, 2014;Subbarayan and Hussain, 2014;Dentici et al, 2015;Lin et al, 2015;Lindsley et al, 2015;Liu et al, 2015;Morgan et al, 2015;Van Laarhoven et al, 2015;Paděrová et al, 2016] and 19 molecularly proven case reports [Kokitsu-Nakata et al, 2012;Riess et al, 2012;Tanaka et al, 2012;Zarate et al, 2012;Brackmann et al, 2013;Kim et al, 2013;Ratbi et al, 2013;Zaidi et al, 2013;Cappuccio et al, 2014;Giordano et al, 2014;Soden et al, 2014;Schulz et al, 2014;Takagi et al, 2014;Verhagen et al, 2014;Gohda et al, 2015;McVeigh et al, 2015;…”

Genetic causes of congenital diaphragmatic hernia

“…One or more cases of the following autosomal dominant conditions have all been described with CDH: Kabuki syndrome with a mutation in KMT2D/MLL2 [80], Baller–Gerold/Saethre–Chötzen with a mutation in TWIST [81], Apert syndrome with craniosynostosis and an FGFR2 mutation [82], SHORT syndrome with a BMP4 mutation [83], tuberos sclerosis type 2 with a TSC2 mutation [84], Beckwith–Wiedemann syndrome with a paternally inherited der(4)t t(4;11)(q33;p14) [85], C-trigonocephaly [86], and multiple pterygium syndrome [87] without identified causes.…”

Neonatal case of novel KMT2D mutation in Kabuki syndrome with severe hypoglycemia

“…Kabuki syndrome is diagnosed clinically on the combination of five main criteria: (i) postnatal growth retardation; (ii) developmental/mental disability; (iii) typical facial features; (iv) skeletal anomalies; and (v) fingertip pads . The present patient had the typical facial features, fingertip pads, and developmental delay, although growth retardation and skeletal findings were not clear.…”

“…Among these KS patients, four had had persistent hypoglycemia and only one was suspected of having hyperinsulinism . Three different KS patients with hyperinsulinemic hypoglycemia were treated with diazoxide (Table ): two patients aged 9 months and 3 years old in the reports had continued diazoxide therapy, and the remaining one patient was able to stop this therapy at 5 years old . The present patient started diazoxide therapy on day 29 after birth and has continued to take this drug at the time of writing.…”