Beyond The Mask: Understanding And Caring For Child With Kabuki Syndrome

Case Scenario: Kabuki Syndrome in a 5 years old male Child, presenting with complaints of persistent developmental delay, speech impairment, and recurrent infections admitted to Tertiary pediatric hospital, Bhubaneswar, Odisha, India`

History of Past Illness:

Child (patient) born at term, weighing 2.6 kg. Early infancy was marked by feeding difficulties and poor weight gain. Motor milestones were delayed: sat at 10 months, walked independently at 24 months. Speech development remained limited, with only single words by age 5. He experienced recurrent respiratory infections (4–6 episodes per year) and two hospitalizations for pneumonia. Genetic evaluation at age 3.5 confirmed Kabuki syndrome.

On examination:

• Anthropometry: weight 12.5 kg (<3rd centile), height 98 cm (<3rd centile), head circumference 48.5 cm (10–25th centile).
• Dysmorphic features: long palpebral fissures with lateral eversion, arched eyebrows, depressed nasal tip, large ears, high-arched palate.
• Neurological: mild hypotonia, gait instability, poor fine motor coordination.
• Cardiac: soft systolic murmur; echocardiogram showed small secundum ASD (4 mm). disability (IQ 50–60).
• Genetics: heterozygous de novo pathogenic KMT2D nonsense variant (c.1234C>T, p.Arg412*).

Introduction

Kabuki syndrome is a rare multisystem developmental disorder first described in Japan in 1981. It is most commonly associated with pathogenic variants in the KMT2D gene and less frequently in KDM6A, leading to disruption of chromatin remodeling and transcriptional regulation. Clinically, affected children present with a characteristic facial gestalt arched eyebrow, long palpebral fissures, depressed nasal tip, and large ears alongside growth deficiency, intellectual disability, congenital heart defects, skeletal anomalies, and immune dysfunction. Because of its broad spectrum of manifestations, Kabuki syndrome requires multidisciplinary management involving pediatricians, cardiologists, therapists, audiologists, ophthalmologists, and genetic specialists. Early recognition is crucial to initiate developmental therapies, monitor systemic complications, and provide family counseling.

Epidemiology

Kabuki syndrome is considered an ultra-rare disorder, but reported prevalence varies widely across regions. In Japan, where the condition was first described, estimates suggest approximately 1 in 32,000 live births, while studies in Australia and New Zealand report a lower frequency of 1 in 86,000 births. Globally, the prevalence is thought to range between 1–9 per 100,000 births, though underdiagnosis remains a major challenge due to phenotypic variability and limited access to genetic testing. Importantly, Kabuki syndrome has been documented across all ethnic groups without sex predilection, underscoring its universal distribution. Recent advances in next-generation sequencing have led to increased recognition of atypical cases, including milder phenotypes that may previously have gone unnoticed. This evolving epidemiological picture highlights the need for heightened awareness among clinicians and nurses, as early identification directly influences developmental outcomes and family counselling.

Etiology and Genetics of Kabuki Syndrome

1. Genetic Basis

KMT2D gene (Kabuki syndrome type 1)

• Located on chromosome 12q13.12.
• Encodes a histone H3 lysine 4 (H3K4) methyltransferase.
• Responsible for adding activating methylation marks to histones, promoting gene transcription.
• Accounts for ~75–80% of cases.
• Inheritance: autosomal dominant, but most cases are de novo (new mutations not inherited from parents).

KDM6A gene (Kabuki syndrome type 2)

• Located on chromosome Xp11.3.
• Encodes a histone H3 lysine 27 (H3K27) demethylase.
• Removes repressive methylation marks, allowing gene activation.
• Accounts for ~5–10% of cases.
• Inheritance: X-linked dominant; males often more severely affected.Other Genetic Insights

Genotype–phenotype correlation:

• KMT2D variants → more frequent congenital heart defects, immune dysfunction.
• KDM6A variants → more severe intellectual disability, growth deficiency.
• Rare reports of mosaicism and familial inheritance exist, but most cases are sporadic.
• Emerging evidence suggests additional genes (e.g., RAP1A, HNRNPK) may produce Kabuki-like phenotypes, though these are less common

Major genes implicated in Kabuki syndrome

Gene	Syndrome	Chromosome	Main protein function	Inheritance
KMT2D	KS type 1	12q13.12	Histone H3K4 methyltransferase	Autosomal dominant
KDM6A	KS type 2	Xp11.3	Histone H3K27 demethylase	X-linked

Figure-1, Clinical Features of kabuki Syndrome

Important Multidisciplinary Care

Children with Kabuki syndrome may require individualized assessment and follow-up involving pediatricians, cardiologists, developmental specialists, physiotherapists, occupational therapists, speech-language therapists, audiologists, ophthalmologists, dentists, dietitians, and genetic specialists, depending on their manifestations.

Priority nursing problems are usually

• Airway/respiratory problems
• Feeding and nutritional problems
• Delayed growth and development
• Impaired mobility
• Communication difficulties
• Risk for infection
• Caregiver knowledge and anxiety

CONCLUSION

Kabuki Syndrome is a rare, multisystem genetic disorder that profoundly impacts growth, development, and overall health. Its etiology lies in mutations of chromatin-modifying genes (KMT2D and KDM6A), which disrupt transcriptional regulation and lead to diverse clinical manifestations. The case of Aarav Kumar highlights the challenges of delayed milestones, recurrent infections, and congenital anomalies, emphasizing the importance of early diagnosis and multidisciplinary care. Epidemiological data confirm KS as an ultra-rare condition, often underdiagnosed due to phenotypic variability. Genetic insights reveal genotype–phenotype correlations that guide prognosis and management. Clinical manifestations span craniofacial, skeletal, cardiac, renal, neurological, and sensory systems, requiring comprehensive diagnostic evaluations. Medical and nursing management focus on surveillance, supportive therapies, and caregiver education. Priority nursing concerns include airway clearance, feeding difficulties, developmental stimulation, infection prevention, mobility support, and communication enhancement. With coordinated multidisciplinary interventions, children with Kabuki Syndrome can achieve improved developmental outcomes and quality of life.

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