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

Kabuki syndrome (KS) is a rare syndrome, characterized by dysmorphic features, congenital abnormalities, and developmental problems. The primary genetic causes are variants in the KMT2D and KDM6A genes. There are few KS patients with KDM6A variants, especially in Turkey. Charcot-Marie-Tooth (CMT) disease, with various subtypes, is the most common inherited peripheral neuropathy.

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 KDM6A, along with a concurrent suspected diagnosis of CMT disease with CNV analysis, not previously reported in the literature. PMP22 duplication was later confirmed in the patient and symptomatic mother with MLPA test.

We report a unique case of dual diagnosis with a novel de novo heterozygous variant in KDM6A and PMP22 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.