Abstract
Objective: By summarizing the clinical characteristics and genetic variations, this study aims to report a case of one child with type I Kabuki syndrome (KS), and to analyze the features and frequency of ocular abnormalities in KS through a retrospective literature review.
Methods: (1) The study focused on a child with KS, collecting clinical data and conducting whole-exome sequencing of the child and the parents' blood DNA, followed by family verification through Sanger sequencing of candidate variants. (2) A literature search was performed using PubMed, the China National Knowledge Infrastructure (CNKI), and Wanfang databases to summarize and analyze cases of KS with ocular abnormalities reported before January 2024.
Results: (1) Genetic testing revealed the patient carried a heterozygous mutation c.11779del (p.Q3927Sfs*52) in the KMT2D gene (NM_003482.3), confirming the diagnosis of autosomal dominant KS type 1. This mutation is reported for the first time as a pathogenic mutation site for KS and is classified as a pathogenic mutation (PVS1+PM2+PM6) according to ACMG standards. (2) Ocular abnormalities are generally present in nearly all KS patients, with long palpebral fissures or ectropion of the outer third of the lower eyelid being characteristic facial manifestations. High-incidence abnormalities include strabismus, blue sclera, ptosis, epicanthal folds, and refractive errors, with prevalence ranging from 10-30%. Other reported ocular abnormalities include eye tissue defects, corneal abnormalities, nystagmus, extraocular muscle cranial nerve paralysis, cataract, optic nerve hypoplasia, abnormal optic disc, Duane syndrome, Marcus Gunn phenomenon, retinal disorders, eyeball atrophy, and tear duct obstruction.
Conclusion: The heterozygous mutation c.11779del (p.Q3927Sfs*52) in the KMT2D gene has been identified as the pathogenic genetic mutation for this child's KS, previously unreported. This study expands the spectrum of genetic mutations and clinical presentations of KS, particularly regarding ocular abnormalities, providing a valuable reference for the diagnosis and genetic counseling of the disease.