A Novel Intronic KMT2D Variant as a Cause of Kabuki Syndrome: A Case Report

Abstract

Kabuki syndrome (KS) is an autosomal dominant genetic disorder in which most cases are caused by de novo mutations. KS type 1 is caused by mutations in KMT2D (OMIM: #147920) and is more common. KS type 2 is caused by mutations in KDM6A (OMIM: #300867). Both genes encode proteins that modify histones and are involved in epigenetic regulation. The enzyme histone-lysine N-methyltransferase 2D, the product of KMT2D, is expressed in most adult tissues and is essential for early embryonic development. The main clinical manifestations of KS include dysmorphic facial features, such as elongated palpebral fissures, eversion of the lateral third of the lower eyelids, and short nasal columella with a broad and depressed nasal tip. Additionally, patients also present with skeletal abnormalities, dermatoglyphic features, mild-to-moderate intellectual disability, hearing loss, and postnatal growth deficiency. We describe an 11-year-old girl from Colombia, who presented with characteristic clinical signs of KS. Genetic studies showed a KMT2D intronic variant (KMT2D NM_003482.3: c.511‐2A> T) as a cause of KS.

Keywords:

• Kabuki syndrome
• coloboma
• rare disease
• RNA splicing
• sensorineural hearing loss

Abbreviations

ACMG, American College of Medical Genetics and Genomics; HSF, Human Splicing Finder; IQ, Intellectual Quotient; KS, Kabuki syndrome; KMT2D, Lysine methyltransferase 2D gene; KDM6A, Lysine Demethylase 6A gene; KMT2D, Lysine methyltransferase 2D; KDM6A, Lysine Demethylase 6A; WISC, Wechsler Intelligence Scale for Children.

Data Sharing Statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Ethics Approval and Informed Consent

This study was approved by the Ethics Committee of Fundacion Valle del Lili, Colombia (human study protocol #1504) and performed in accordance with the ethical standards found in the Declaration of Helsinki. Written informed consent was obtained from the parents of the subjects. Information revealing the subject’s identity was not included in the manuscript. The patient was identified by number and not by her real name.

Consent for Publication

Institutional approval was required to publish the case details. All the images and patient material presented in this study have been consented for publication and they are available to see upon request.

Acknowledgments

We thank the patient and her parents for agreeing to the pub HSF: Human Splicing Finder publication of this report. We also thank the people who have contributed to the development and execution of this study.

Author Contributions

All authors contributed to data analysis, drafting or revising the article, have agreed on the journal to which the article will be submitted, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors have no conflicts of interest to declare.

Additional information

Funding

All forms of support and funding for study design, data collection, data analysis and manuscript writing were provided by the employers of the authors (Universidad Icesi and Fundación Valle del Lili).