Kabuki Syndrome and Charcot-Marie-Tooth Disease Co-Occurrence: Unique Case with Novel Variant

Abstract

<b><i>Introduction:</i></b> Kabuki syndrome (KS) is a rare syndrome, characterized by dysmorphic features, congenital abnormalities, and developmental problems. The primary genetic causes are variants in the <i>KMT2D</i> and <i>KDM6A</i> genes. There are few KS patients with <i>KDM6A</i> variants, especially in Turkey. Charcot-Marie-Tooth (CMT) disease, with various subtypes, is the most common inherited peripheral neuropathy. <b><i>Case Presentation:</i></b> We present a case of a 7-year-old girl with characteristic dysmorphic features, neonatal hypotonia, developmental delay, and short stature. Exome sequencing revealed a novel heterozygous variant in <i>KDM6A</i>, along with a concurrent suspected diagnosis of CMT disease with CNV analysis, not previously reported in the literature. <i>PMP22</i> duplication was later confirmed in the patient and symptomatic mother with MLPA test. <b><i>Conclusion:</i></b> We report a unique case of dual diagnosis with a novel de novo heterozygous variant in <i>KDM6A </i>and <i>PMP22 </i>duplication in the same patient, highlighting the additive use of exome sequencing for CNVs and, moreover, unraveling the complexity of rare diseases, particularly when multiple conditions coexist.