Börjeson-Forssman-Lehmann Syndrome
Börjeson-Forssman-Lehmann Syndrome (BFLS)
Key Points
- X-linked intellectual disability syndrome
- Characterized by distinctive facial features, obesity, and hypogonadism
- Caused by mutations in PHF6 gene
- Affects predominantly males
- First described in 1962 by Mats Börjeson
BFLS is a rare genetic condition characterized by intellectual disability, obesity, seizures, and distinctive facial and physical features. The syndrome primarily affects males, though female carriers may show mild features.
Major Clinical Manifestations
Craniofacial Features
- Large ears
- Deep-set eyes
- Heavy supraorbital ridges
- Broad nasal tip
- Coarse facial features
- Prominent supraorbital ridges
Physical Features
- Truncal obesity (develops in early childhood)
- Gynecomastia
- Short stature
- Small genitalia
- Tapered fingers
Neurological Features
- Moderate to severe intellectual disability
- Seizures (in ~50% of cases)
- Hypotonia in infancy
- Delayed developmental milestones
- Behavioral problems
Endocrine Abnormalities
- Hypogonadism
- Delayed or absent puberty
- Growth hormone deficiency
Genetic Basis
Inheritance Pattern
- X-linked recessive inheritance
- Located on Xq26.3
- PHF6 gene mutations
Molecular Genetics
The PHF6 gene provides instructions for making a protein that regulates gene activity and plays a crucial role in nervous system development. Mutations in this gene lead to:
- Altered protein function
- Disrupted gene regulation
- Impaired nervous system development
Genetic Testing
- Sequence analysis of PHF6
- Deletion/duplication analysis
- Family studies for carrier detection
Diagnostic Criteria and Evaluation
Clinical Diagnosis
- Comprehensive physical examination
- Family history assessment
- Developmental evaluation
- Growth monitoring
Laboratory Studies
- Endocrine evaluation
- Genetic testing for PHF6 mutations
- Thyroid function tests
- Growth hormone levels
Imaging Studies
- Brain MRI
- Skeletal survey
- Bone age studies
Treatment and Care Approaches
Multidisciplinary Care
- Pediatric endocrinologist
- Developmental pediatrician
- Neurologist
- Physical therapist
- Occupational therapist
- Speech therapist
Specific Interventions
- Early intervention programs
- Hormone replacement therapy when indicated
- Anticonvulsant medications if seizures present
- Weight management strategies
- Physical therapy for hypotonia
Monitoring and Follow-up
- Regular growth monitoring
- Developmental assessments
- Endocrine function evaluation
- Vision and hearing screening
- Behavioral assessment
