Legius Syndrome

Excerpt

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 SPRED1 identified by molecular genetic testing.

Management: Treatment of manifestations: 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.

Surveillance: 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 SPRED1 pathogenic variant has a 50% chance of inheriting the pathogenic variant. Once the SPRED1 pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.