Kallmann Syndrome
Kallmann Syndrome
A rare genetic disorder characterized by hypogonadotropic hypogonadism and anosmia/hyposmia.
Key Points
- Prevalence: 1:10,000 males; 1:50,000 females
- Characterized by absent/delayed puberty
- Associated with defective GnRH neuron migration
- Various inheritance patterns (X-linked, autosomal dominant, autosomal recessive)
Clinical Manifestations
Primary Features
- Anosmia/Hyposmia (90-95% cases)
- Delayed/absent puberty
- Incomplete sexual development
- Cryptorchidism in males (30-40%)
- Primary amenorrhea in females
Associated Features
- Midline defects:
- Cleft lip/palate
- Dental agenesis
- High-arched palate
- Neurological:
- Mirror movements (synkinesia)
- Hearing impairment
- Balance problems
- Skeletal abnormalities
- Renal agenesis (unilateral)
Diagnostic Approach
Laboratory Studies
- Hormone levels:
- Low/absent serum FSH and LH
- Low testosterone (males)
- Low estradiol (females)
- GnRH stimulation test
- Genetic testing for known mutations
Imaging
- MRI of olfactory system
- Renal ultrasound
- Bone age X-ray
Additional Tests
- Formal smell testing
- Audiometry
- Dental examination
Treatment Strategies
Hormone Replacement
- Males:
- Testosterone replacement
- hCG/FSH for fertility
- Females:
- Estrogen/progesterone replacement
- GnRH pump for fertility
Monitoring
- Regular hormone level checks
- Bone density monitoring
- Growth velocity in children
- Fertility assessment
Additional Care
- Psychological support
- Genetic counseling
- Regular dental care
- Management of associated conditions
Genetic Basis
Known Genes
- KAL1 (ANOS1) - X-linked
- FGFR1 - Autosomal dominant
- PROKR2 - Autosomal recessive/dominant
- PROK2 - Autosomal recessive
- CHD7 - Autosomal dominant
Inheritance Patterns
- X-linked recessive (14%)
- Autosomal dominant (30%)
- Autosomal recessive (15%)
- Oligogenic inheritance
Genetic Testing
- Next-generation sequencing panels
- Family screening recommendations
- Genetic counseling implications
