Cafe-Au-Lait Spots, Multiple

Clinical Features

Multiple cafe-au-lait spots, which are the diagnostic hallmark of neurofibromatosis I (NF1; 162200), have been observed in families in which there have been no other changes of NF1 (Riccardi, 1980). The absence of neurofibromas and Lisch nodules of the iris suggests that these families are expressing a trait genetically distinct from NF1.

Charrow et al. (1993) reported a family with multiple cafe-au-lait spots with no other features of NF1 in 4 generations, with male-to-male transmission in the first 2 generations.

Charrow et al. (1993) excluded linkage to NF1 on chromosome 17 in a family with multiple cafe-au-lait spots. Brunner et al. (1993) likewise excluded the NF1 locus as the site of the mutation in this disorder by demonstrating that an affected woman had transmitted a different haplotype for markers flanking the NF1 gene (613113) to each of her 2 affected daughters.

Abeliovich et al. (1995) showed close linkage between multiple cafe-au-lait spots and the NF1 locus in a 3-generation family with 1 affected subject. They concluded that the trait was allelic to NF1, that it is fully penetrant, and that it does not confer a risk of other NF1 symptoms. Thus, there may be 2 forms of multiple cafe-au-lait spots, a form linked to NF1 and an unlinked form.