Kallmanns syndrome
🧩 The classic clue is a boy with delayed puberty and anosmia (loss of smell).
This reflects the embryological failure of GnRH neurons to migrate alongside olfactory neurons.
🧠 About Kallmann's Syndrome
- Inherited form of secondary hypogonadism (hypogonadotropic hypogonadism).
- Caused by congenital failure of olfactory lobe development and GnRH deficiency.
- Often presents in adolescence with absent puberty and impaired sense of smell.
🧬 Genetics
- Modes of inheritance: X-linked recessive (XLR), autosomal dominant (AD), or autosomal recessive (AR).
- Mutations in KAL1 (anosmin-1) or FGFR1 (KAL2) genes implicated.
- ~50% of cases have identifiable genetic mutations; others are sporadic.
⚙️ Aetiology & Pathophysiology
- Failure of GnRH-secreting neurons to migrate to the hypothalamus during embryogenesis.
- Lack of GnRH → ↓ LH & FSH → reduced testosterone/oestradiol → delayed or absent puberty.
- Olfactory bulb aplasia/atrophy explains anosmia.
🤒 Clinical Features
- 🚫 Anosmia or hyposmia (loss/reduced smell).
- 🧑🦱 Delayed puberty or absent secondary sexual characteristics.
- 👨 Cryptorchidism, small testes, micropenis (in males).
- Associated anomalies: cleft lip/palate, colour blindness, renal agenesis, hearing loss, mirror movements (synkinesia).
🔬 Investigations
- 🧪 Hormones: ↓ Testosterone, ↓/inappropriately normal LH & FSH.
- 🧑⚕️ Differentiate from primary hypogonadism (↑ LH/FSH, e.g. in Klinefelter’s).
- 🧲 MRI brain: absent olfactory bulbs, pituitary assessment.
- 🧬 Genetic testing (FISH / sequencing) for confirmation.
💊 Management
- 💉 Hormone replacement therapy: Testosterone (males) or oestrogen/progesterone (females).
- 🧪 Pulsatile GnRH or gonadotropin therapy (hCG/FSH) to induce fertility if desired.
- 👨👩👧 Genetic counselling for affected families.
- 🤝 Supportive care: psychological support, fertility planning, monitoring bone health.
