Legius Syndrome

CLINICAL CHARACTERISTICS

Legius syndrome is characterized by multiple café au lait macules without neurofibromas or other tumor manifestations of neurofibromatosis type 1 (NF1). Additional clinical manifestations commonly reported include intertriginous freckling, lipomas, macrocephaly, and learning disabilities, attention-deficit/hyperactivity disorder (ADHD), and developmental delays.

DIAGNOSIS/TESTING: The diagnosis of Legius syndrome is established in a proband with suggestive findings and a heterozygous pathogenic variant in identified by molecular genetic testing.

MANAGEMENT

Consideration of behavioral modification and/or pharmacologic therapy for those with ADHD; physical, speech, and occupational therapy for those with identified developmental delays; individualized education plans for those with learning disorders; referral to dermatologist as needed for lipoma management; treatment of pectus excavatum and scoliosis per orthopedist; standard treatment for seizures per experienced neurologist; referral to otolaryngologist for those with identified hearing loss. Monitor developmental progress, educational needs, and behavioral assessment at each visit; assess for pigmentary lesions, lipomas, scoliosis, and new-onset seizures at each visit; hearing evaluation as needed.

GENETIC COUNSELING

Legius syndrome is inherited in an autosomal dominant manner. Many individuals diagnosed with Legius syndrome have an affected parent. Each child of an individual with Legius syndrome caused by a germline pathogenic variant has a 50% chance of inheriting the pathogenic variant. Once the pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.