Cafe Au Lait Spots

Updated: May 19, 2020
  • Author: Nazanin Saedi, MD; Chief Editor: Dirk M Elston, MD  more...
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Café au lait spots, or café au lait (CAL) macules (CALMs), are hyperpigmented lesions that may vary in color from light brown to dark brown; [1] this is reflected by the name of the condition, which means "coffee with milk." The borders may be smooth or irregular.

The size and number of café au lait skin lesions widely vary and are usually the earliest manifestations of neurofibromatosis. [2] The macules may be observed in infancy, although they are typically very light in infants and can be difficult to appreciate. The skin lesions develop in early infancy, and they may enlarge in size and become obvious after age 2 years.

Café au lait macules are observed in 95% of patients with neurofibromatosis type 1 (NF1), which is the most frequently occurring neurocutaneous syndrome. These spots may also be observed in patients without NF1. Other conditions in which they may be observed include McCune-Albright syndrome, tuberous sclerosis, Fanconi anemia, and Coffin-Siris syndrome (MIM 135900), characterized by developmental delay, speech impairment, distinctive facial features, hypertrichosis, hypoplasia of the distal phalanx of the fifth digit, and agenesis of the corpus callosum. [3]  Café au lait macules may be a marker for RASopathies, disorders related to RAS mutations. [4]

The images below depict various café au lait lesions.

Axillary freckling showing café au lait spots. Axillary freckling showing café au lait spots.
Multiple irregular sized and shaped café au lait l Multiple irregular sized and shaped café au lait lesions.
Café au lait lesions. Café au lait lesions.
Café au lait lesions. Café au lait lesions.


Café au lait spots are caused by an increase in melanin content, often with the presence of giant melanosomes. A significant increase in melanocyte density is noted in the café au lait macules of patients with NF1 compared with patients who have isolated café au lait macules without NF1 involvement. Also, an increase in stem cell factor cytokines is more frequently observed in NF1 café au lait macules than non-NF1 café au lait macules.



Café au lait macules associated with NF1 result from an autosomal dominant disorder with high penetrance and variability in the expression of clinical features.

The NF1 gene is localized to the pericentromeric region of the long arm of chromosome 17. The gene encodes for neurofibromin, which is a GTP-ase activating protein that downregulates cellular proto-oncogene, p21-ras.

About 50% of individuals with NF1 have a spontaneous mutation. The high incidence of new mutations is thought to result from the large size of the gene, which increases the likelihood of spontaneous mutations.

Occasionally, patients who have larger gene deletions have a higher incidence of mental retardation and earlier appearance of cutaneous neurofibromas.




United States

In the newborn period, solitary café au lait spots may occur in 0.3% of whites, 3% of Hispanics, and in 18% of blacks. [5] In childhood, solitary café au lait macules occur in 13% of whites and 27% of blacks. Two or more café au lait macules were not observed in any of 4000 white newborns, although they were found in 8% of black newborns. Café au lait spots that confirm the diagnosis of NF1 occur at an estimated frequency of 1 in 3500 persons. [6]


Solitary café au lait spots occur in 0.5% of Arab newborns and in 0.4% of Chinese newborns. [5]


Café au lait spots are more frequently observed in black children.


No sexual predilection is recognized.


Typically, café au lait spots are present at birth, although they may be difficult to appreciate. A Wood lamp may improve the ability to visualize these faint spots. By the time the child is aged 2-3 years, café au lait macules are clearly visible. The size and number of café au lait macules increase with patient age in patients with NF1.



No reports indicate that café au lait macules undergo malignant change. Café au lait macules are benign and produce no mortality or morbidity, although the associated syndromes may have significant manifestations.