Infrequent Manifestations of Kabuki Syndrome in a Patient with Novel MLL2 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.

Keywords: Diaphragmatic hernia; Hypoglycemia; Kabuki syndrome; MLL2.

Fig. 1

Left: patient at 9 months of age with typical dysmorphic features. Right, top: right-sided microtia. Right, middle: hypoplastic 5th fingernail. Right, bottom: fingertip pads.

Fig. 2

Sequencing analysis of the MLL2 gene. The sequencing analysis detected 2 previously unreported changes. The first alteration, c.9931C>T (p.Q3311X), is shown in A. The second change, shown in B, is a c.10101G>T (p.L3367F). Neither change was detected in the parents of the proband, indicating that both alterations are de novo. Asterisks: mutant and normal nucleotide in the proband and the parents, respectively.

Fig. 3

Allele-specific PCR and sequencing analysis of the MLL2 gene. A forward PCR primer was designed to be specific for the c.9931C>T (p.Q3311X) mutation in the MLL2 gene. PCR utilizing this allele-specific primer amplified only the patient's DNA (upper panel: lane 1, 100-bp ladder; lane 2, DNA from a normal control; lane 3, DNA from the proband; and lane 4, no DNA control). Sequence analysis of the proband's allele-specific PCR product detected the c.10101G>T (p.L3367F) variant (asterisk), indicating that both alterations are in cis (lower panel).