Makindo Medical Notes

🧩 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.