Brauer Syndrome (Setleis Syndrome)
Brauer Syndrome (Setleis Syndrome)
Brauer syndrome, also known as Setleis syndrome or focal facial dermal dysplasia type III (FFDD3), is a rare genetic condition characterized by distinctive facial features and dermal abnormalities. It belongs to the group of focal facial dermal dysplasias.
Key Points
- Rare autosomal recessive inheritance pattern
- Characterized by distinctive facial features present at birth
- Associated with TWIST2 gene mutations
- Part of the focal facial dermal dysplasia spectrum
- Variable expressivity among affected individuals
Epidemiology
- Extremely rare disorder with fewer than 50 reported cases
- Affects males and females equally
- Higher prevalence in Puerto Rican populations
- Can occur in any ethnic group
Historical Context
- First described by Brauer in 1929
- Further characterized by Setleis in 1963
- Genetic basis identified in the early 2000s
- Classification as FFDD3 established in 2011
Clinical Features
Facial Features
- Primary Characteristics:
- Bilateral temporal marks resembling forceps marks
- Leonine appearance with coarse features
- Absent or sparse eyelashes
- Multiple periocular papules
- Puckered chin
- Secondary Features:
- Upslanting palpebral fissures
- Flattened nasal bridge
- Thick vermilion of lips
- Facial asymmetry
- Abnormal hair growth patterns
Dermatological Manifestations
- Skin Findings:
- Bitemporal scar-like lesions
- Dermal atrophy or aplasia
- Abnormal skin texture
- Altered pigmentation
- Hair Abnormalities:
- Sparse or absent eyelashes
- Abnormal eyebrow patterns
- Unusual scalp hair distribution
- Variable body hair patterns
Associated Features
- Growth and development usually normal
- Normal intelligence
- Possible ocular complications
- Dental anomalies in some cases
- Potential hearing impairment
Diagnosis & Genetics
Diagnostic Approach
- Clinical Diagnosis:
- Based on characteristic facial features
- Family history assessment
- Physical examination
- Documentation of temporal lesions
- Genetic Testing:
- TWIST2 gene sequencing
- Next-generation sequencing panels
- Whole exome sequencing if needed
Molecular Genetics
- TWIST2 Gene:
- Located on chromosome 2q37.3
- Basic helix-loop-helix transcription factor
- Role in mesodermal development
- Multiple pathogenic variants identified
- Inheritance Pattern:
- Autosomal recessive transmission
- Variable expressivity
- Genetic counseling important
Differential Diagnosis
- Other focal facial dermal dysplasias
- Bitemporal aplasia cutis congenita
- Kabuki syndrome
- Ablepharon macrostomia syndrome
- Ectodermal dysplasias
Histopathology
- Dermal hypoplasia
- Abnormal collagen organization
- Reduced elastic fibers
- Altered appendageal structures
Management
Multidisciplinary Care
- Core Team Members:
- Clinical geneticist
- Dermatologist
- Plastic surgeon
- Ophthalmologist
- Pediatrician
- Support Services:
- Genetic counseling
- Psychological support
- Social work services
- Educational support
Treatment Options
- Dermatological Care:
- Skin protection measures
- Moisturizing regimens
- Treatment of complications
- Scar management
- Surgical Interventions:
- Reconstructive procedures
- Scar revision
- Aesthetic improvements
- Timing considerations
- Ophthalmologic Care:
- Regular eye examinations
- Management of corneal exposure
- Protection of ocular surface
- Treatment of complications
Research & Development
Current Research
- Molecular Studies:
- TWIST2 function investigation
- Genetic modifier studies
- Developmental pathway research
- Animal models
- Clinical Research:
- Natural history studies
- Treatment outcome analysis
- Quality of life assessments
- Genotype-phenotype correlations
Future Directions
- Gene therapy possibilities
- Novel treatment approaches
- Improved diagnostic methods
- Patient registry development
Prognosis & Care
Long-term Outcomes
- Normal life expectancy
- Variable cosmetic concerns
- Psychosocial challenges
- Quality of life impact
Monitoring Guidelines
- Regular Follow-up:
- Annual genetic assessment
- Biannual dermatology review
- Regular ophthalmology checks
- Developmental monitoring
- Specific Monitoring:
- Growth parameters
- Ocular complications
- Skin changes
- Psychosocial adjustment
Support Resources
- Patient support groups
- Educational resources
- Family counseling
- Community services
