Is there an association between cafe-au-lait (cafe-au-lait macules) macules on the trunk, Mongolian spots, and dermal nevi (dermal nevus)?

Association Between Café-au-Lait Macules, Mongolian Spots, and Dermal Nevi

There is no established direct association between café-au-lait macules on the trunk, Mongolian spots, and dermal nevi as a specific combined entity, though these cutaneous findings may coexist in certain genetic syndromes, particularly those affecting neural crest-derived cells.

Relationship Between These Cutaneous Findings

Café-au-Lait Macules

• Well-circumscribed, evenly pigmented macules/patches ranging from 1-2mm to >20cm in diameter
• Common in healthy children but multiple lesions may indicate underlying genetic conditions
• Most significant association is with neurofibromatosis type 1 (NF1) and Legius syndrome

Mongolian Spots

• Classified as intermediate-risk cutaneous anomalies in current guidelines 1
• Generally considered benign when isolated
• Blue-gray macular pigmentation typically found on the lumbosacral area or buttocks
• Usually fade over time in most children

Dermal Nevi

• May coexist with other pigmentary disorders but generally represent a separate entity
• No established direct pathogenic link with café-au-lait macules or Mongolian spots in isolation

Genetic Syndromes Where These Findings May Coexist

Neurofibromatosis Type 1 (NF1)

• Characterized by multiple café-au-lait macules (≥6 spots >5mm in prepubertal individuals or >15mm in postpubertal individuals)
• Diagnostic evaluation is often initiated due to clinical signs like café-au-lait macules 1
• Dermal melanocytic nevi have been reported in NF1 patients 2
• Rare cases of mosaic NF1 with giant café-au-lait macule, plexiform neurofibroma and multiple melanocytic nevi have been documented 3

RASopathies

• Legius syndrome (LS) presents with café-au-lait macules and skinfold freckling similar to NF1 1
• Important to differentiate from NF1 as cancer surveillance recommendations differ significantly 1
• No specific cancer surveillance is recommended for Legius syndrome 1
• Other RASopathies like Noonan syndrome with multiple lentigines (NSML) may present with pigmentary changes

Clinical Significance and Evaluation

When to Pursue Genetic Evaluation

• Multiple café-au-lait macules (≥6)
• Large segmental café-au-lait macules
• Café-au-lait macules with associated facial dysmorphism
• Family history of genetic syndromes
• Additional cutaneous findings such as axillary/inguinal freckling

Risk Stratification

• Isolated café-au-lait spots are classified as "low risk" cutaneous markers 1
• Mongolian spots are classified as "intermediate risk" cutaneous markers 1
• The combination of these findings should prompt consideration of underlying genetic conditions

Conclusion

While these three cutaneous findings (café-au-lait macules, Mongolian spots, and dermal nevi) can occasionally coexist, there is no established direct pathogenic association between them as a specific combined entity. Their co-occurrence should prompt consideration of underlying genetic syndromes, particularly those affecting neural crest-derived cells like melanocytes and Schwann cells. Genetic testing may be warranted when multiple café-au-lait macules are present or when there are other concerning features suggestive of a RASopathy or other genetic syndrome.