What is the management approach for Kabuki syndrome?

Kabuki Syndrome: Management Approach

Kabuki syndrome requires multidisciplinary, symptom-oriented management focused on developmental support, surveillance for multisystem complications, and genetic counseling, as there is no curative treatment available. 1, 2

Genetic Confirmation and Counseling

• Molecular genetic testing should be performed to confirm the diagnosis, targeting KMT2D (responsible for up to 75% of cases) and KDM6A (responsible for up to 5% of cases) through direct Sanger sequencing or whole exome sequencing 2, 3
• Genetic counseling is essential for families, as most cases result from de novo variants, though inherited pathogenic variants can occur 2
• Approximately 20% of cases remain genetically unexplained despite testing, requiring clinical diagnosis based on characteristic features 2, 4

Core Diagnostic Criteria for Management Planning

Current diagnostic criteria include: hypotonia during infancy, developmental delay and/or intellectual disability, typical dysmorphic features (elongated palpebral fissures, depressed nasal tip, prominent ears, arched eyebrows), and confirmed pathogenic variant in KMT2D or KDM6A 2, 3

Developmental and Neurological Management

• Early intervention programs are critical, focusing on physical therapy for hypotonia, occupational therapy for motor delays, and speech therapy for communication difficulties 1, 2
• Psychomotor development monitoring should occur throughout childhood with regular developmental assessments 2
• Educational support tailored to the degree of intellectual disability (which is variable but present in most cases) is essential 1, 3
• Behavioral issues including autistic features may require specialized psychological interventions and behavioral therapy 2, 5

Multisystem Surveillance and Specialist Care

Cardiac Monitoring

• Echocardiography should be performed at diagnosis to screen for congenital heart defects, which occur in a significant proportion of patients 2, 3
• Cardiology follow-up is indicated based on findings, as cardiac anomalies are among the most clinically significant complications 3, 5

Growth and Endocrine Management

• Monitor growth parameters regularly, as poor physical growth and short stature are common features 2, 3
• Screen for endocrinological anomalies including obesity and other metabolic disturbances that can develop 4

Gastrointestinal and Renal Surveillance

• Evaluate for gastrointestinal anomalies at diagnosis and monitor for feeding difficulties 2, 5
• Renal ultrasound should be performed to identify structural kidney abnormalities 2, 3

Immunological Assessment

• Screen for immunological defects, as immune dysfunction can predispose to recurrent infections 3, 4
• Consider immunology referral if recurrent infections occur 3

Musculoskeletal Care

• Monitor for scoliosis development with regular clinical examination and radiographs as indicated 2, 5
• Orthopedic referral for skeletal abnormalities including vertebral anomalies 3, 5

Psychosocial Support

• Family counseling and support are important, as caregivers face challenges related to the child's developmental delays and medical complexity 1
• Psychotherapeutic approaches should address the unique socio-emotional delays seen in KS patients 1
• Connect families with support groups and resources specific to Kabuki syndrome 1, 5

Critical Management Gaps and Pitfalls

• Clinical management remains fragmented without established clinical care standards, highlighting the need for coordinated multidisciplinary care 5
• The clinical phenotype shows notable variability between individuals, requiring individualized surveillance plans based on specific manifestations 5, 4
• Early diagnosis is essential for optimal management of complications, which can be numerous and interpenetrating 4
• Adult phenotype, life expectancy, and long-term outcomes remain poorly characterized, representing significant knowledge gaps 5

Primary Care Physician Role

• Primary care physicians should coordinate specialist referrals and maintain longitudinal oversight of the comprehensive care plan 1, 3
• Increased awareness and recognition of KS among clinicians is crucial for timely diagnosis and appropriate management 3
• Regular monitoring of developmental milestones, growth parameters, and screening for system-specific complications should occur at routine visits 2, 3