Focal Dermal Hypoplasia (Goltz-Gorlin Syndrome)
Focal Dermal Hypoplasia (Goltz-Gorlin Syndrome)
Definition
Focal Dermal Hypoplasia (FDH) is a rare genetic multisystem disorder characterized by distinctive skin abnormalities and a wide spectrum of defects affecting multiple organ systems including the eyes, teeth, skeletal, urinary, gastrointestinal, cardiovascular, and central nervous systems.
Key Points
- X-linked dominant inheritance pattern
- Predominantly affects females (90% of cases)
- Usually lethal in males
- Caused by mutations in PORCN gene
- Variable expressivity
- Significant impact on quality of life
Epidemiology
- Incidence: Less than 1 in 100,000 live births
- Female predominance (male:female ratio ≈ 1:9)
- No ethnic predilection
- Usually diagnosed in early infancy
Clinical Features
Cutaneous Manifestations
- Primary Skin Findings:
- Linear atrophic lesions following Blaschko's lines
- Telangiectatic areas
- Hyperpigmentation and hypopigmentation
- Fat herniations through dermal defects
- Raspberry-like papillomas (periorificial)
- Distribution:
- Asymmetric involvement
- Predominant on trunk and extremities
- Face involvement common
- Additional Features:
- Sparse, brittle hair
- Patchy alopecia
- Nail dystrophy
- Asymmetric breast development
Skeletal Abnormalities
- Extremities:
- Syndactyly
- Ectrodactyly (lobster claw deformity)
- Oligodactyly
- Clinodactyly
- Facial Features:
- Asymmetric facial features
- Pointed chin
- Small ears
- Notched alae nasi
- Other:
- Osteopathia striata
- Scoliosis
- Short stature
- Asymmetric limb development
Ocular Manifestations
- Structural Abnormalities:
- Colobomas of iris, retina, and choroid
- Microphthalmia
- Strabismus
- Anophthalmia (rare)
- Additional Features:
- Photophobia
- Corneal opacity
- Nystagmus
- Ectopic pupils
Diagnostic Approach
Clinical Diagnosis
- Major Criteria:
- Characteristic skin manifestations
- Limb abnormalities
- Dental anomalies
- Supporting Features:
- Family history
- X-linked inheritance pattern
- Multiple system involvement
Laboratory Studies
- Genetic Testing:
- PORCN gene sequencing
- Deletion/duplication analysis
- X-inactivation studies in females
- Imaging Studies:
- Skeletal radiographs
- Echocardiogram
- Brain MRI if indicated
- Ophthalmologic examination
Differential Diagnosis
- Incontinentia Pigmenti
- CHILD Syndrome
- Rothmund-Thomson Syndrome
- EEC Syndrome
- Aplasia Cutis Congenita
Treatment and Management
Multidisciplinary Care
- Core Team:
- Pediatric Dermatologist
- Clinical Geneticist
- Orthopedic Surgeon
- Ophthalmologist
- Plastic Surgeon
- Dental Specialist
- Additional Specialists:
- Physical Therapist
- Occupational Therapist
- Speech Therapist
- Psychological Support
Specific Interventions
- Skin Management:
- Regular moisturization
- Sun protection
- Treatment of papillomas
- Management of skin infections
- Surgical Interventions:
- Correction of skeletal deformities
- Management of fat herniations
- Dental procedures
- Cosmetic procedures
- Supportive Care:
- Pain management
- Nutritional support
- Physical therapy
- Occupational therapy
Genetics and Pathophysiology
Genetic Basis
- Gene Information:
- PORCN gene mutation
- Located on X chromosome (Xp11.23)
- Codes for O-acyltransferase
- Essential for WNT signaling
- Inheritance Pattern:
- X-linked dominant
- 95% new mutations
- 5% inherited from affected mother
- Usually lethal in males
Molecular Mechanisms
- WNT Signaling:
- Disrupted WNT protein modification
- Altered cell signaling
- Impact on embryonic development
- Effects on tissue formation
- Developmental Impact:
- Ectodermal tissue formation
- Mesodermal development
- Organogenesis
- Pattern formation
Special Considerations
Pregnancy and Genetic Counseling
- Prenatal Considerations:
- Genetic testing options
- Prenatal diagnosis possible
- Risk assessment
- Inheritance patterns discussion
- Family Planning:
- 50% risk of transmission to offspring
- Preimplantation genetic diagnosis option
- Discussion of severity spectrum
Quality of Life
- Psychosocial Impact:
- Body image concerns
- Social adjustment
- Educational support needs
- Family support systems
- Long-term Outcomes:
- Variable severity
- Normal life expectancy in most cases
- Reproductive considerations
- Occupational adaptations
Disclaimer
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