Kenny-Caffey Syndrome
Kenny-Caffey Syndrome
Overview
Kenny-Caffey Syndrome (KCS) is a rare genetic disorder characterized by growth delays, distinctive facial features, skeletal abnormalities, and abnormal calcium levels. Two types exist: Type 1 (KCS1) and Type 2 (KCS2).
Key Points
- First described by Kenny and Caffey in 1966
- Characterized by:
- Short stature
- Cortical thickening of long bones
- Hypocalcemia
- Distinctive facial features
- Two genetic types:
- Type 1: Autosomal recessive (TBCE gene)
- Type 2: Autosomal dominant (FAM111A gene)
Epidemiology
- Extremely rare condition
- Fewer than 100 reported cases worldwide
- Higher prevalence in Middle Eastern populations
- No gender predilection
Clinical Manifestations
Growth and Development
- Prenatal growth retardation
- Proportionate short stature
- Growth hormone deficiency
- Delayed bone age
- Variable developmental delay
Craniofacial Features
- Small, deep-set eyes
- Microphthalmia
- Prominent forehead
- Thick eyebrows
- Depressed nasal bridge
- Micrognathia
- Dental anomalies
- Delayed tooth eruption
- Enamel hypoplasia
- Malformed teeth
Skeletal Manifestations
- Cortical thickening of long bones
- Medullary stenosis
- Osteosclerosis
- Short, thick long bones
- Small hands and feet
- Delayed fontanel closure
Endocrine Abnormalities
- Hypoparathyroidism
- Hypocalcemia
- Hyperphosphatemia
- Low PTH levels
- Growth hormone deficiency (in some cases)
Other Features
- Recurrent infections
- Visual problems
- Intellectual disability (variable)
- Seizures (due to hypocalcemia)
Genetic Basis
Type 1 (KCS1)
- TBCE gene mutations
- Located on chromosome 1q42.3
- Encodes tubulin-specific chaperone E
- Autosomal recessive inheritance
Type 2 (KCS2)
- FAM111A gene mutations
- Located on chromosome 11q12.1
- Encodes family with sequence similarity 111 member A
- Autosomal dominant inheritance
Genotype-Phenotype Correlations
- Type 1: Generally more severe
- Type 2: More variable expression
- Ongoing research for specific correlations
Diagnostic Approach
Clinical Diagnosis
- Based on characteristic features:
- Growth parameters
- Facial features
- Skeletal findings
- Calcium homeostasis abnormalities
Laboratory Studies
- Calcium metabolism
- Serum calcium
- Serum phosphorus
- Parathyroid hormone
- Vitamin D levels
- Growth hormone studies
- Complete blood count
- Immunological studies
Imaging Studies
- Skeletal radiographs
- Bone age assessment
- Brain MRI
- Ophthalmological imaging
Genetic Testing
- TBCE gene sequencing
- FAM111A gene sequencing
- Family studies when appropriate
Treatment and Management
Multidisciplinary Care
- Pediatric endocrinologist
- Clinical geneticist
- Orthopedic specialist
- Ophthalmologist
- Developmental specialist
- Dental specialist
Specific Interventions
- Calcium Homeostasis
- Calcium supplementation
- Vitamin D supplementation
- Regular monitoring
- Emergency protocols for hypocalcemia
- Growth Management
- Growth hormone therapy (if indicated)
- Regular growth monitoring
- Nutritional support
- Skeletal Care
- Orthopedic monitoring
- Physical therapy
- Prevention of fractures
- Developmental Support
- Early intervention
- Educational support
- Occupational therapy
Monitoring
- Regular calcium monitoring
- Growth assessment
- Developmental evaluation
- Vision screening
- Dental care
- Immunological status
Current Research
Active Areas of Investigation
- Natural history studies
- Genotype-phenotype correlations
- Novel therapeutic approaches
- Long-term outcomes
Current Clinical Trials
- Registry studies
- Treatment protocols
- Quality of life studies
