Legius syndrome

Legius syndrome is characterized by multiple café-au-lait spots, with or without freckles and macrocephaly.

Epidemiology

More than 200 cases were reported between 2007 and 2013 .

Although rare, it is estimated that up to 2% of patients fulfilling diagnostic criteria for neurofibromatosis-1 (without NF1 gene mutations) have Legius syndrome.

Clinical presentation

Besides the characteristic café-au-lait spots, other possible findings are:

  • freckles
  • macrocephaly.
  • pectus excavatum or carinatum
  • Noonan-like face
  • lipomas
  • learning disabilities and behavioral problems (less severe than in NF1)

Pathology

The disease is caused by a heterozygous mutation in the SPRED1 gene, which acts as a negative regulator of RAS pathway and interacts with neurofibromin, the product of the NF1 gene.

Many different allelic variants have been found, however, without genotype-phenotype correlation.

History and etymology

Legius syndrome was named after Eric Legius who is credited with first describing it.

Siehe auch: