Rapp-Hodgkin Syndrome
Rapp-Hodgkin Syndrome (RHS)
Rapp-Hodgkin syndrome is a rare form of ectodermal dysplasia characterized by distinctive craniofacial features, cleft lip/palate, hypohidrotic ectodermal dysplasia, and genital abnormalities. It is now considered part of the TP63-related disorders spectrum.
Key Points
- Prevalence: < 1/1,000,000
- Inheritance: Autosomal dominant
- Gene: TP63 mutations
- Age of Onset: Congenital
- Complete penetrance with variable expressivity
- Often confused with AEC syndrome (Hay-Wells syndrome)
Clinical Manifestations
1. Craniofacial Features
- Facial Characteristics:
- Distinctive facies
- Small narrow nose
- Narrow nasal passages
- Maxillary hypoplasia
- Low-set ears
- Cleft Abnormalities:
- Cleft lip and/or palate
- Bifid uvula
- High-arched palate
- Submucous cleft
- Distinctive facies
- Growth Parameters:
- Normal intelligence
- Short stature in some cases
- Microcephaly possible
2. Ectodermal Features
- Hair Abnormalities:
- Sparse, wiry hair
- Progressive worsening
- Abnormal texture
- Patchy distribution
- Eyebrow/Eyelash involvement
- Body hair reduction
- Sparse, wiry hair
- Skin Manifestations:
- Hypohidrosis
- Heat intolerance
- Temperature dysregulation
- Skin texture abnormalities
- Palmoplantar hyperkeratosis
- Hypohidrosis
- Nail Dystrophy:
- All nails affected
- Progressive changes
- Thick, discolored nails
3. Dental Abnormalities
- Structural Issues:
- Hypodontia
- Microdontia
- Enamel defects
- Cone-shaped teeth
- Developmental Issues:
- Delayed eruption
- Abnormal spacing
- Malocclusion
4. Associated Features
- Genitourinary:
- Hypospadias in males
- Lacrimal duct abnormalities
- Urinary tract infections
- Respiratory:
- Chronic rhinitis
- Recurrent infections
- Upper airway obstruction
Genetic Basis & Inheritance
Molecular Genetics
- TP63 Gene:
- Location: Chromosome 3q27
- Function:
- Transcription factor
- Epithelial development
- Limb formation
- Cell cycle regulation
- Mutation Types:
- Missense mutations
- Frameshift mutations
- Splice site variants
- Deletions
- Genotype-Phenotype Correlations:
- Variable expressivity
- Complete penetrance
- Interfamilial variation
Developmental Course & Natural History
Prenatal Period
- Potential Findings:
- Cleft lip detection
- Growth parameters
- Amniotic fluid volume
Neonatal Period
- Immediate Concerns:
- Feeding difficulties
- Temperature regulation
- Respiratory issues
Childhood Development
- Growth Patterns:
- Height velocity
- Weight gain
- Head circumference
- Developmental Milestones:
- Usually normal cognitive development
- Possible speech delay due to cleft
- Motor development typically normal
Diagnostic Approach
Clinical Diagnosis
- Major Criteria:
- Characteristic facial features
- Cleft lip/palate
- Hair abnormalities
- Ectodermal dysplasia features
- Supporting Features:
- Family history
- Associated anomalies
Genetic Testing
- Molecular Analysis:
- TP63 sequencing
- Deletion/duplication testing
- Next-generation sequencing panels
- Family Studies:
- Parental testing
- Sibling evaluation
Treatment & Management
1. Multidisciplinary Care
- Team Composition:
- Clinical geneticist
- Pediatric dentist
- Plastic surgeon
- ENT specialist
- Speech therapist
- Dermatologist
2. Specific Interventions
- Craniofacial Management:
- Cleft repair timing
- Orthodontic intervention
- Speech therapy
- Feeding support
- Dermatological Care:
- Skin care regimen
- Temperature management
- Hair care protocols
- Dental Management:
- Early intervention
- Prosthetic planning
- Preventive care
3. Supportive Care
- Quality of Life:
- Psychological support
- Educational support
- Family counseling
- Preventive Measures:
- Infection prevention
- Regular monitoring
- Growth assessment
Differential Diagnosis
Similar Syndromes
- AEC Syndrome (Hay-Wells):
- Most similar phenotype
- Key differences:
- Severity of skin erosions
- Pattern of hair involvement
- EEC Syndrome:
- Overlapping features
- Additional limb involvement
- Other TP63-Related Disorders:
- ADULT syndrome
- LMS syndrome
- Split-hand/foot malformation
Complications & Long-term Outcomes
Medical Complications
- Respiratory:
- Chronic infections
- Airway problems
- Sleep apnea
- Dermatological:
- Skin infections
- Heat intolerance
- Chronic dermatitis
- Dental:
- Caries risk
- Periodontal disease
- Malocclusion
Psychosocial Impact
- Social Challenges:
- Peer relationships
- School adaptation
- Self-image concerns
- Support Needs:
- Family counseling
- Educational support
- Social integration
