What is the management approach for Kabuki syndrome?

Kabuki Syndrome Management

Kabuki syndrome requires coordinated multidisciplinary care focused on early identification and management of specific organ system complications, with genetic confirmation through KMT2D or KDM6A testing to guide surveillance and family counseling. 1, 2

Diagnostic Confirmation

• Genetic testing is essential for definitive diagnosis, with KMT2D variants accounting for up to 75% of cases and KDM6A variants causing approximately 5% of cases 3, 2
• Clinical diagnosis requires hypotonia during infancy, developmental delay and/or intellectual disability, characteristic facial dysmorphism (elongated palpebral fissures, arched eyebrows, depressed nasal tip, prominent ears), and confirmed pathogenic variant in KMT2D or KDM6A 2
• Exome sequencing should be pursued when clinical suspicion is high but initial targeted testing is negative, as approximately 20% of cases remain genetically unexplained 3, 1

Surveillance and Monitoring Framework

Cardiac Evaluation

• Echocardiography at diagnosis to screen for congenital heart defects, which are common in Kabuki syndrome 1, 2
• Cardiology follow-up based on initial findings, with repeat imaging if new symptoms develop 1

Growth and Endocrine Monitoring

• Serial growth measurements at every visit during childhood, as poor physical growth is characteristic 2
• Endocrine evaluation for growth hormone deficiency, thyroid dysfunction, and precocious puberty, which occur with increased frequency 3, 1
• Monitor for obesity development, particularly in adolescence 3

Renal and Gastrointestinal Assessment

• Renal ultrasound at diagnosis to identify structural anomalies 1, 2
• Monitor for feeding difficulties, gastroesophageal reflux, and constipation throughout childhood 1
• Assess for recurrent infections and consider immunological evaluation if frequent 3

Musculoskeletal Care

• Orthopedic evaluation for scoliosis, joint hypermobility, and skeletal anomalies 2
• Physical therapy for hypotonia, which is present during infancy in most cases 2
• Monitor for progressive spinal deformities requiring intervention 1

Neurodevelopmental Support

• Early intervention services including physical therapy, occupational therapy, and speech therapy starting in infancy 4, 2
• Neuropsychological assessment to characterize intellectual disability severity and guide educational planning 5, 1
• Behavioral evaluation for autistic features, which occur variably 2
• Special education services tailored to the degree of developmental delay 5, 4

Hearing and Vision

• Audiological screening at diagnosis and periodically, as hearing loss can occur 1
• Ophthalmological evaluation for refractive errors and other ocular abnormalities 1

Psychosocial and Family Support

• Primary care coordination is critical, with the nurse practitioner or physician serving as gatekeeper to coordinate specialty services 4
• Monitor caregiver fatigue and impact on siblings, directing families to appropriate support services 4
• Genetic counseling for families regarding recurrence risk, as most cases are de novo but inherited cases occur 3, 2
• Psychotherapeutic support for behavioral and socio-emotional delays, which are frequently present but often overlooked 5

Emerging Genotype-Phenotype Considerations

• Clinical variability is substantial between affected individuals, with an emerging genotype-phenotype correlation suggesting KMT2D versus KDM6A variants may predict different phenotypic features 1
• Autoimmune disorders occur more frequently than in the general population and should be monitored 3
• Life expectancy and adult phenotype remain poorly characterized, highlighting the need for lifelong surveillance 1

Critical Management Pitfalls

• Delayed diagnosis is common because physical features may be subtle at birth and become more pronounced during childhood, sometimes taking months to years for recognition 4, 3
• Misdiagnosis as other conditions (intellectual disability of unknown cause, isolated autism spectrum disorder) delays appropriate multidisciplinary care 5
• Fragmented care without a coordinating provider leads to missed complications and inadequate family support 4, 1
• Failure to provide genetic testing prevents accurate diagnosis, family counseling, and appropriate surveillance 3, 2