Makindo Medical Notes

Related Subjects: |Neurofibromatosis Type 1 |Neurofibromatosis Type 2 |Tuberous sclerosis |Café-au-lait spots |McCune Albright syndrome

☕ Introduction

Café-au-lait spots (CALMs) are flat, light to dark brown skin macules named from the French term meaning “coffee with milk.” They may appear at birth or develop in early childhood and are usually benign. However, the number, size, and pattern of these lesions can serve as important clinical clues to underlying genetic syndromes. While a few isolated spots are common in healthy individuals, multiple or large café-au-lait macules may warrant further assessment.

🔍 Definition and Appearance

• Size: Vary from a few millimetres to several centimetres in diameter.
• Shape: Typically oval or round with smooth, well-defined margins — often described as having a “coast of California” appearance.
• Colour: Uniform light tan to deep brown pigmentation; intensity may darken with age or sun exposure.
• Distribution: May occur anywhere on the body but often seen on the trunk, buttocks, or limbs.

🧠 Clinical Significance

Café-au-lait macules may be an isolated finding or part of a systemic genetic condition.

• 🧬 Neurofibromatosis Type 1 (NF1): The most frequent association. Diagnostic criteria include:
  • ≥6 café-au-lait macules >5 mm in diameter (prepubertal) or >15 mm (postpubertal).
  • Plus other features such as neurofibromas, Lisch nodules, optic glioma, axillary/inguinal freckling, or a first-degree relative with NF1.

  💡 Tip: In NF1, café-au-lait macules often appear in infancy and may increase in number and size during early childhood.

• ⚖️ McCune–Albright Syndrome (MAS): Café-au-lait patches in MAS tend to have irregular, jagged borders — the “coast of Maine” pattern — and typically respect the midline. They are associated with polyostotic fibrous dysplasia and endocrine hyperfunction (e.g. precocious puberty, hyperthyroidism, Cushing’s syndrome).
• 🧩 Other Associations: Rarely seen with Legius syndrome (NF1-like without neurofibromas) or Noonan–NF1 overlap syndromes.

🔬 Pathophysiology

CALMs result from increased melanin production by melanocytes and augmented melanosome transfer to keratinocytes. In syndromic cases like NF1, mutations in the NF1 gene on chromosome 17 cause loss of neurofibromin, a tumour suppressor that regulates Ras–MAPK signalling — leading to dysregulated cell growth and pigmentation.

🧾 Diagnosis

• Number and Size: ≥6 lesions exceeding the defined size threshold suggests NF1 and requires further evaluation.
• Associated Features: Neurofibromas, axillary freckling, Lisch nodules, or bony dysplasia indicate syndromic involvement.
• Family History: Positive family history supports an autosomal dominant inheritance pattern (NF1 or Legius syndrome).
• Skin Examination: Perform full-body inspection under good lighting; dermatoscopy may show homogenous pigmentation.
• Genetic Testing: NF1 gene sequencing can confirm the diagnosis where uncertain.

🩺 Management and Follow-Up

• ✅ Benign lesions: Café-au-lait spots alone do not require treatment and are medically harmless.
• 🔍 Regular Screening: Children with multiple CALMs should have periodic review for new cutaneous, neurological, or ophthalmic signs of NF1.
• 👪 Genetic Counselling: Recommended for affected families, particularly with autosomal dominant syndromes.
• 🎨 Cosmetic Management: Laser therapy (e.g. Q-switched Nd:YAG) may be used for cosmetic reasons, though recurrence is possible.
• 🧠 Multidisciplinary Care: In syndromic cases, coordinate follow-up with dermatology, neurology, ophthalmology, and genetics teams.

✅ Summary Table