A Case of Kabuki Syndrome Caused by a Novel Mutation in KMT2D and a Literature Review of Ocular Abnormalities

doi:10.21203/rs.3.rs-4277300/v1

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Case Report

A Case of Kabuki Syndrome Caused by a Novel Mutation in KMT2D and a Literature Review of Ocular Abnormalities

https://doi.org/10.21203/rs.3.rs-4277300/v1

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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.

Kabuki Syndrome (KS)

Eye Abnormalities

KMT2D

Novel Mutation

Case Report

Kabuki syndrome (KS) was first described in Japan in 1981 by teams led by Niikawa[1] and Kuroki[2], representing a rare genetic syndrome that affects multiple organs and systems. The estimated incidence rate of this disease is 1 in 32,000 newborns in Japan, and 1 in 86,000 in newborns in Australia and New Zealand, with the similar speculated incidence rates in non-Japanese populations speculated to be similar to those in Japanese populations based on other literature reports[3, 4]. The name "Kabuki syndrome" derives from the facial features of patients, such as elongated palpebral fissures and eversion of the lateral third of the lower eyelids, resembling those of traditional Japanese Kabuki actors. In 1988, Niikawa et al. identified five typical clinical manifestations in 62 Japanese KS patients: characteristic facial features, postnatal growth deficiency, mild to moderate intellectual disability, skeletal anomalies, and dermatoglyphic abnormalities. In 2018, an international expert group proposed the international consensus diagnostic criteria for KS[5]. Any male or female patient of any age with infantile hypotonia, developmental delay and/or intellectual disability, and one or two of the following major criteria, can be diagnosed with KS: Major indicators: (1) Pathogenic and likely pathogenic variants in KMT2D or KDM6A; (2) Characteristic facial features during some stage of life: long palpebral fissures with eversion of the lower third of the eyelids and two of the following: ① arched and broad eyebrows with a notch in the outer 1/3 or sparse eyebrows; ② short columella, depressed nasal tip; ③ large, cupped ears; ④ fetal fat pads. Given the diverse array of organs affected in KS, the severity of symptoms can vary across different organ systems. Most patients are diagnosed with molecular diagnostics after the clinical phenotype becomes apparent, often presenting with intellectual developmental delay and growth retardation. Current advancements in research indicates genetic mutations as the main cause of this disease. In 2010, the KMT2D gene (located at 12q13.12, consisting of 56 exons) was identified as the pathogenic gene for KS, with subsequent mutation screening in KS cohorts revealing that the patients were caused by mutations in the KMT2D gene[7]. Moreover, in 2012, Lederer et al. reported another pathogenic gene for KS, KDM6A (located at Xp11.3, consisting of 32 exons), and following studies confirmed that about 12.5% of KS patients were caused by mutations in the KDM6A gene[8, 9]. KS with KMT2D gene mutations was defined as type 1 (OMIM ID: 147920), with an autosomal dominant inheritance; KS with KDM6A gene mutations was defined as type 2 (OMIM ID: 300867), with an X-linked dominant inheritance[10]. Furthermore, other genes such as RAP1A/RAP1B, HNRNPK, ZMIZ1 have also been reported to cause KS-like symptoms, including reports of mosaicism[11]. This study conducts molecular screening on a KS child patient with strabismus to clarify the molecular etiology. Also, it synthesizes data from both domestic and and international KS cases, by analyzing the characteristics and frequency of ocular abnormalities in this disease. This comprehensive analysis contributes to early recognition, intervention, and prevention of ocular complications.

2.1 Case Details

In this case, a 4-year-and-2-month-old female patient visited the Shenzhen Eye Hospital on January 2, 2024, presenting with symptoms of tearing in both eyes with esotropia. Her medical history is as follows: she was delivered by emergency cesarean section at 37 weeks due to intrauterine distress, with a birth weight of 2,090g and a history of birth hypoxia. She had multiple admissions at the ages of 5 months, 9 months, 1 year and 7 months, and 2 years and 8 months due to observed developmental delays in mental and motor skills. Assessment using the children’s mental development scale indicated her with developmental quotient below normal, with lagging behind physiological age in all aspects. Also, the Alberta Infant Motor Scale (AIMS) showed a total score of 11, percentile <5, indicating that she was below 5% compared to her peers. Moreover, brain MRI revealed slight enlargement of the bilateral lateral ventricles, sinusitis, and bilateral otomastoiditis; Furthermore, the Auditory Brainstem Response (ABR) suggested bilateral hearing abnormalities, more pronounced on the left; Electrocardiography (ECG) also showed complete right bundle branch block; lumbar-sacral spine (AP/lateral) showed spina bifida occulta. The patient’s discharge diagnoses displayed developmental delay in mental and motor skills, congenital foot deformity, patent foramen ovale, patent ductus arteriosus, complete right bundle branch block, congenital hypothyroidism, ABO incompatibility hemolytic disease, spina bifida occulta, auditory abnormality, sinusitis, bilateral otomastoiditis. On the other hand, her parents are healthy, non-consanguineous marriage, with 2 healthy brothers, and no reported family history of any genetic diseases(Figure 1). The physical examination (Figure 2) revealed distinct facial features, including developmental delay, a broad forehead, high hairline, arched eyebrows, sparse hair in the outer 1/3 of the eyebrows, long palpebral fissures, ectropion in the outer 1/3 of the lower eyelids, esotropia, left proptosis, short nasal columella, flat nasal tip, high-arched palate, lop ears. As for abnormal dermatoglyphics, there are prominent fingertip pads on both hands, short fifth finger with a single transverse crease. Also, skeletal abnormalities were noted as bilateral valgus deformity of feet. In terms of the ophthalmic examination, it showed mild proptosis in the left eye, normal lacrimal puncta, slight ectropion in the outer 1/3 of the lower lid, conjunctiva without obvious hyperemia, clear cornea, anterior chamber clear, pupils 3*3 mm, lens clear, no obvious abnormalities in the fundus. The assessment of her ocular position showed corneal reflex test: +10°, right eye dominant squint, alternating cover test (30cm): ocular alignment from inward to normal, about 15°, limited eye movement, left eye inferior movement -2, right eye lateral movement -1, nystagmus, poor cooperation during examination. As for the auxiliary examinations, the results showed refraction of OD +1.00DS; OS +1.25DS/-0.25DC*34° (poor cooperation); The nystagmus tracking test showed horizontal tremor amplitude 2.6°, speed 81.3°/s, vertical tremor amplitude 3.1°, speed 96.9°/s; no obvious abnormalities in binocular SLO, OCT.(Figure 3)

2.2 Methods

2.2.1 DNA Extraction: anticoagulated peripheral venous blood samples were collected from the patient and her parents for the separation of genomic DNA.

2.2.2 Whole Exome Sequencing (WES): The child's genome underwent WES with an average sequencing depth of 100×. The sequencing results were aligned with the human reference genome to filter candidate pathogenic mutations. Variants identified by WES were screened through databases such as the Online Mendelian Inheritance in Man (OMIM), the 1000 Genomes Project, the Human Gene Mutation Database (HGMD), and the NCBI Clinical Variant Database. Tools like SIFT, Polyphen-2, and Mutation Taster were utilized for pathogenicity prediction analysis of the mutation sites.

2.2.3 Sanger Sequencing: Suspected pathogenic mutation sites were validated in the child and their parents using Sanger sequencing.

3.1 Genetic Testing Results

The patient carries a mutation in the KMT2D gene (Fig. 3): NM 003482.3; exon 39; c.11779del; p.Q3927Sfs*52. This variant has not been previously reported or included in professional databases such as HGMD or ClinVar. The mutation disrupts the gene's open reading frame, leading to a functional alteration in the protein [PVS1]. Moreover, this variant is absent in the Exome Aggregation Consortium (ExAC), the 1000 Genomes Project (1000G), or the Genome Aggregation Database (gnomAD)[PM2]. The variant is a de novo mutation not identified through parental consanguinity [PM6]. Based on the current evidence, this variant can be classified as pathogenic.

3.2 Literature Review Analysis

Table 1

Summary of the Incidence Rates of Various Ocular Abnormalities in KS Patients from Four Previous Studies
Eye Abnormalities	66 cases[12]	200 cases[13]	300 cases[14]	341 cases[15]
Long palpebral fissure or ectropion of the outer one-third of the lower eyelid	40(60.6%)	/	286(95.3%)	/
refractive errors	17(25.8%)	/	/	/
Amblyopia	5(7.6%)	6(3%)	/	/
Eyelid ptosis	9(13.6%)	1(0.5%)	65(21.7%)	/
Strabismus	22(33.3%)	43(21.5%)	/	70(20.5%)
Ptosis of the upper eyelid	17(25.8%)	20(10%)	27(9%)	49(14.4%)
Ocular tissue deficiency	19(28.8%)	9(4.5%)	/	11(3.2%)
Corneal abnormalities	9(13.6%)	5(2.5%)	/	10(2.9%)
Nystagmus	4(6.1%)	1(0.5%)	/	4(1.2%)
Blue sclera	16(24.2%)	44(22%)	50(16.7%)	/
Ocular motor cranial nerve palsy	/	4(2.0%)	/	4(1.2%)
Cataract	2(3.0%)	3(1.5%)	/	3(0.9%)
Optic nerve hypoplasia	1(1.5%)	/	/	3(0.9%)
Optic disc abnormalities	1(1.5%)	/	/	2(0.6%)
Duane Syndrome	/	/	/	2(0.6%)
Marcus Gunn phenomenon	3(4.5%)	/	/	2(0.6%)
Retinal pathology	6(9.1%)	1(0.5%)	/	2(0.6%)
Ocular atrophy	/	1(0.5%)	/	/
Nasolacrimal duct obstruction	1(1.5%)	1(0.5%)	/	/

We conducted a review of four previous studies that statistically analyzed the incidence rates of various ocular abnormalities in KS patients and performed a summary analysis, results of which are presented in Table 1. It is important to note that the objectives of each study were different, and the structural or functional ocular abnormalities included in the statistics varied. Therefore, the absence of an abnormality in the statistics does not necessarily imply its absence in reality. Additionally, elongated palpebral fissures or eversion of the outer third of the lower eyelids, characteristic facial manifestations of KS, were included in two of the studies, with incidence rates of 60.6% and 95.3%, respectively. Other ocular abnormalities with relatively high incidence rates include strabismus, blue sclera, ptosis, epicanthal folds, and refractive errors, with reported incidence rates of approximately 10–30%. However, it should be noted that most cases did not provide a complete clinical description. Thus, these frequencies should be considered as the minimum incidence rates. In other words, the actual incidence rates of ocular abnormalities may be higher.

This study has identified the heterozygous mutation c.11779del (p.Q3927Sfs*52) in the KMT2D gene as the pathogenic genetic mutation for KS in the child, representing a previously unreported and novel variant. In addition, by reviewing relevant literature and summarizing reports of KS cases both domestically and internationally, our study delves into a comprehensive review the characteristics and incidence rates of ocular abnormalities associated with KS.

KS is a rare congenital anomaly syndrome characterized by distinctive facial features, skeletal abnormalities, postnatal growth retardation, intellectual disability, and various other anomalies such as auditory dysfunction, cardiac defects, dermatoglyphic abnormalities, genitourinary anomalies, and ophthalmic abnormalities. Additional clinical manifestations include cleft lip or palate, hypotonia, persistent fetal finger pads, immunodeficiency, as well as gastrointestinal, renal, and vertebral anomalies. Notably,, the syndrome may be challenging to diagnose in newborns and infants due to less pronounced facial features during these stages[16]. The pathogenesis of KS has been associated with mutations in two key genes, namely the KMT2D and KDM6A. Specifically, mutations in the KMT2D gene, located on chromosome 12 and inherited in an autosomal dominant manner, lead to type I KS. The KMT2D gene encodes a histone H3 lysine 4 (H3K4)-specific methyltransferase, with enzymatic activity governed by the SET domain of the KMT2D protein. On the one hand, methylation of H3K4, a genome-wide mark associated with gene activation, targets 75% of human gene transcription start sites. On the other hand, mutations in the KMT2D gene disrupt H3K4 methylation, inhibiting the transcription of numerous developmentally important genes, leading to multi-organ involvement and a range of KS phenotype[17]. Moreover, the KDM6A gene, located on the X chromosome and inherited in an X-linked dominant manner, causes type II KS and encodes a histone H3 lysine-27 demethylase. Histone lysine methyltransferases and demethylases play a central role in chromatin organization and gene expression through the dynamic regulation of histone lysine methylation[18]. Type I KS is generally caused by KMT2D gene mutations, and often presents with more pronounced facial features and is more likely to have cardiac anomalies, neurodevelopmental issues, and tumor occurrence [19]. In comparison, type II KS is generally resulted from KDM6A gene mutations, which is more likely to present with hypoglycemia and feeding difficulties, accompanied by poor growth and prepubertal short stature[20].

In this case, the child presented with a broad forehead, high hairline, arched eyebrows, sparse hair on the outer third of the eyebrows, long palpebral fissures, ectropion in the outer third of the lower eyelids, esotropia, abnormal eye movements, left eye proptosis, nystagmus, short nasal columella, flat nasal tip, high-arched palate, lop ears, prominent fingertip pads, a short fifth finger with a single transverse crease, bilateral valgus deformity of the feet, and other distinctive signs. Additionally, there were signs of developmental delay in mental and motor skills, patent foramen ovale, patent ductus arteriosus, complete right bundle branch block, congenital hypothyroidism, ABO incompatibility hemolytic disease, spina bifida occulta, auditory abnormalities, sinusitis, and bilateral otomastoiditis, indicating multi-system damage. These clinical manifestations are consistent with the phenotype criteria for KS, leading to a preliminary diagnosis of KS. Also, genetic testing and bioinformatics analysis indicated that the child carries a heterozygous frameshift mutation in the KMT2D gene (NM_003482.3), c.11779del (p.Q3927Sfs*52). This mutation represents a deletion at position 11779 of the NM_003482.3 transcript compared to the reference sequence, which leads to a frameshift. As a result, the 3927th amino acid changing from glutamine to serine causes the stop codon in the polypeptide sequence to shift to position 52. This affects the C-terminal domain of the protein, specifically the SET domain, thus impacting the H3K4 methylation transcription activation mechanism. This inhibition of transcription for multiple development-related genes leads to multi-organ involvement in KS, resulting in the observed KS phenotype. Combining clinical phenotype with genetic testing results, the child was diagnosed with type I KS, representing a novel pathogenic variant. This case further enriches the clinical phenotype spectrum and gene mutation spectrum of KS, therefore, providing more reference data for the clinical diagnosis, differential diagnosis, and genetic counseling of this condition.

The abnormality of the eyes has been defined as the primary clinical diagnostic sign of KS, which is present in almost all KS patients[21].In 2000, Kluijt et al. published the more comprehensive review at that time of ophthalmic manifestations in KS patients. Specifically, they summarized 200 KS cases. Moreover, in 2001, Wessel et al. expanded the compiled cases to 300 KS patients[14]. Furthermore, in 2003, Ming et al. described retinal and/or iris defects in 3 cases of KS children, finding structural or functional eye abnormalities in 126 out of 384 reported KS patients (37%) published before 2002[15]. In 2021, Merdler-Rabinowicz et al. summarized the ocular abnormalities of KS patients reported in the literature since 2002, comparing these cases with previously reported cases, most of which underwent genetic testing validation and more comprehensive ophthalmic evaluation[12].

Based on the research mentioned above, reported KS ocular abnormalities include long palpebral fissures or ectropion of the outer 1/3 of the lower eyelid, eyelid redundancy, strabismus, blue sclera, ptosis, Marcus Gunn phenomenon, refractive errors, ocular tissue defects, corneal abnormalities, nystagmus, amblyopia, extraocular muscle cranial nerve palsy, Duane syndrome, cataracts, retinal lesions, optic nerve hypoplasia, optic disc abnormalities, and lacrimal duct obstruction. The most common abnormalities, including long palpebral fissure, ectropion of the outer 1/3 of the lower eyelid, and eyelid redundancy, are classified as periorbital malformations. These malformations are characterized by the underdevelopment of the orbicularis oculi muscle. Despite that they may not lead to severe visual issues, they can result in problems such as tearing and incomplete eyelid closure. What should be noted is that severe cases may lead to dry eye syndrome, corneal exposure, and other complications. In such situations, in addition to aesthetic considerations, surgical correction is also recommended to prevent corneal and conjunctival dryness that could potentially affect eye function. To be specific, surgery can involve both internal and external eyelid procedures, including partial closure of the outer aspect of the eyelid, correction of ectropion of the outer 1/3 of the lower eyelid, and removal of excess eyelid redundancy[22].

Included in the analysis of four selected literature pieces in this study, higher prevalence rates of other ocular abnormalities are noted for strabismus, blue sclera, the Marcus Gunn phenomenon, and refractive errors.

Currently, there are numerous reported cases of strabismus among KS patients, although many of these reports lack detailed descriptions. Only a few instances describ significant angles of congenital esotropia or minor degrees of strabismus that are easily overlooked. The etiology of strabismus is complex and related to genetics and ocular development, often caused by asymmetrical development of the extraocular muscles in children. Orbital magnetic resonance imaging can be used to assess changes in muscle pathways associated with observed ocular motility pathologies. Additionally, prolonged strabismus has a certain impact on stereopsis but is challenging to assess, as diminished stereopsis can also result from intellectual disabilities in patients[23]. Treatment for strabismus in KS patients advocates careful monitoring before intervention, as the angle of strabismus may change over time. There are reports of a case with a significant angle of approximately 70 prism diopters in youth, which decreased to about 45–50 prism diopters over time with refractive error correction [24].

Blue sclera refers to a primary collagen defect in the sclera, leading to thinning and translucency, which exposes the underlying vessels and resulting in a bluish to bluish-gray appearance[25]. This characteristic feature can be observed in various genetic syndromes, non-genetic diseases, and certain medication side effects, with at least 66 genetic syndromes reported to have blue sclera, including KS[26]. The presence of blue sclera should prompt physicians to conduct a detailed review of the patient's medical condition to ascertain the underlying cause. Typically, blue sclera caused by congenital developmental anomalies does not manifest with abnormal symptoms and does not require necessitate specific treatment.

The Marcus Gunn phenomenon, also known as jaw-winking syndrome, is characterized by the rapid exaggerated elevation of the ptotic upper eyelid when the jaw moves, occurring unilaterally in cases of congenital ptosis and represents about 2% of congenital ptosis cases. This phenomenon is believed to result from an abnormal connection between the motor branch of the trigeminal nerve, which innervates the levator palpebrae superioris muscle, and the oculomotor nerve, which innervates the other extraocular muscles. Current theories propose that damage to the affected cranial nerve within the uterus leads to secondary degeneration of the involved cranial nerve nucleus and a re-emergence of embryonic primitive reflex movements.[27] Although there have been few reported cases of the Marcus Gunn phenomenon in KS patients, the proportion is relatively low. Correcting Marcus Gunn syndrome often requires multiple surgeries, and the choice of corrective procedures depends on the severity of ptosis, the functionality of the levator palpebrae superioris muscle, and the experience and preferences of the surgeon. The primary goal of surgery is to address the abnormal connection between the eyelid and jaw movements[28]

The prevalence of refractive errors and amblyopia in KS patients may be underestimated due to the lack of visions and refractive assessments in many individuals with intellectual disabilities Early assessment of visual acuity and refractive status is crucial for timely intervention and treatment, which can help reduce or prevent irreversible visual impairments from occurring[21]. Moreover, eye tissue defects in KS patients encompass abnormalities in the eyelids, iris-ciliary body, choroid, retina, or optic nerve. The ocular manifestations of these defects in KS patients vary widely, with the degree of refractive errors and amblyopia being related to the location and size of the defects. In the fundus, variability includes the size (anteroposterior and transverse range) of the defects and the involvement of the optic disc and macula. While fundamental birth defects cannot be corrected, many complications can be largely avoided, such as prophylactic laser retinal photocoagulation at the margins of choroidal defects[29].

Corneal abnormalities in KS include microcornea, corneal opacities, corneal vascularization, and Corneal abnormalities observed in KS include microcornea, corneal opacities, corneal vascularization, and corneal dystrophy. Microcornea may result from developmental stasis or excessive development of the anterior segment during infancy, leading to reduced corneal development space. It often coexists with eye tissue defects and microphthalmia. In utero corneal developmental abnormalities have been shown to result in congenital corneal keloids, which are confirmed to be associated with KMT2D mutations[30]. Bilateral congenital corneal opacities have been described as an early ocular manifestation of KS, representing a rare condition characterized by congenital loss of corneal tissue transparency. This condition typically originates between the 6th and 16th week of pregnancy, and bilateral corneal transplantation can be performed after birth to prevent depriving amblyopia[31] Reports of congenital cataracts associated with KS have also been documented. The primary cause of congenital cataracts is genetic disorders, with autosomal dominant inheritance being the most common. Congenital cataracts exhibit significant genetic and phenotypic heterogeneity, with a complex pathogenesis. However, specific research on the causative mechanism of cataracts related to KS is currently lacking. In addition, KS-related retinal abnormalities that have been reported include retinal pigment degeneration, macular malnutrition or deposits, retinal capillary dilatation, and retinal detachment[32–35].

Other rare eye abnormalities in KS patients include optic nerve hypoplasia, optic disc anomalies, eyeball atrophy, nasolacrimal duct obstruction, lacrimal punctum abnormalities, among others[36–38]. There are, however, fewer reported cases and studies focusing on these abnormalities, primarily addressing symptomatic treatments such as intravitreal anti-angiogenic injections for vitreous cavity, retinal detachment repair, and lacrimal duct reconstruction. Due to the lack of comprehensive clinical descriptions in most cases, insufficient attention has been given to eye abnormalities. Consequently, the frequency of eye abnormalities in this study should be considered as the minimum occurrence rate, and the actual occurrence rate of eye abnormalities may be higher. This paper offers a comprehensive analysis of the characteristics and occurrence frequency of eye abnormalities in KS. Such analysis is of significant importance for ophthalmologists receiving KS patients as their initial consult for eye abnormalities. Also, it aids in early identification, intervention, and prevention of ocular complications.

This study has identified the heterozygous mutation c.11779del (p.Q3927Sfs*52) in the KMT2D gene as a novel mutation responsible for Kabuki syndrome (KS). Through a retrospective analysis of reported characteristics and occurrence frequencies of eye abnormalities in KS patients, this study significantly enriched the genetic mutation spectrum and clinical presentation data of KS, particularly in relation to eye abnormalities. These findings serve as a valuable reference basis for the diagnosis and genetic counseling of this condition.

Ethics approval and consent to participate

The case report in this article has obtained written consent from the patient's family and complies with relevant ethical standards. We have made every effort to protect the patient's privacy and rights, and to avoid causing any harm. Furthermore, the research presented in this article has been reviewed and approved by the ethics review board of Shenzhen Eye Hospital (Ethics approval number: 2024-015(Research)-01). No conflicts of interest were identified during the preparation of this article.

Consent for publication

The parents have agreed to publish and sign the informed consent form.

Availability of data and materials

All data generated or analysed during this study are included in this published article (and its supplementary information files).

Competing interests

The authors declare that they have no competing interests.

Funding

No.

Authors' contributions

YX Z and LY contributed to the conception of the manuscript. YX Z wrote the manuscript. XN C draw the pattern diagrams. All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication. All authors read and approved the final manuscript.

Acknowledgements

Not applicable.

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No competing interests reported.

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A Case of Kabuki Syndrome Caused by a Novel Mutation in KMT2D and a Literature Review of Ocular Abnormalities

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Abstract

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1. Introduction

2. Materials and Methods

3. Results

3.1 Genetic Testing Results

3.2 Literature Review Analysis

4. Discussion

5. Conclusion

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