A Diagnostic Dilemma: Concurrent Diagnosis of Cystic Fibrosis and Definitive Kabuki Syndrome Type 1

The article presents a clinical case involving a patient with presumptive coexistence of two hereditary disorders, confirmed by molecular genetic analyses. Clinical evaluation of the proband, a 9-year-old girl, revealed features characteristic of Kabuki syndrome, including a typical "Kabuki makeup" facial phenotype, short stature, intracranial hypertension, and diffuse muscular hypotonia. Additional clinical findings included chronic right-sided otitis media, conjunctivitis, recurrent pneumonia, bilateral conductive hearing loss, astigmatism, and primary adenitis. Clinical assessment and molecular genetic testing were performed. High-throughput sequencing identified a previously reported pathogenic heterozygous variant in the <i>KMT2D</i> gene, NM_003482.4:c.15142C>T p.Arg5048Cys, and two known heterozygous variants in the <i>CFTR</i> gene: NM_000492.4:c.1521_1523delCTT p.Phe508del and c.3454G>C p.Asp1152His, classified as pathogenic and of variable clinical significance, respectively. Segregation analysis demonstrated that the <i>KMT2D</i> variant most likely arose in the proband de novo, whereas the <i>CFTR</i> variants were inherited from each of the parents. Notably, the proband's clinically unaffected elder sister carried the same <i>CFTR</i> genotype. Based on the clinical presentation and molecular genetic findings, the diagnosis of Kabuki syndrome type 1 was conclusively established in the patient. Functional assessment of CFTR demonstrated its preserved function, which did not support a diagnosis of CF or CFTR-related disorders.