LZTR1-associated café au lait macules in a pediatric patient with atypical clinical presentation

Summary: Abstract Body: A 3-year-old male presented with numerous café au lait macules (CALMs). Previous genetic testing for NF1 and SPRED1 were negative. Physical examination revealed eight ill-defined, geometrically shaped light brown patches on the trunk, flank, thighs, and arm, some with a surrounding halo. The CALMs were stable in size and number, and the patient was asymptomatic with no significant family history of related syndromes. An ultrasound of the thigh, given the surrounding halo, was performed, which showed no significant findings. Further genetic testing, including the RASopathies and Noonan Spectrum Disorders Panel, identified a variant in the LZTR1 gene (c.1397G>A (p.Arg466Gln)). LZTR1 is associated with LZTR1-related schwannomatosis and Noonan syndrome. LZTR1-related schwannomatosis involves the development of multiple non-intradermal and non-vestibular schwannomas in adulthood, often accompanied by chronic pain. Noonan syndrome is a disorder characterized by cardiovascular abnormalities, short stature, distinctive facial features, café au lait spots, developmental delay, and the development of both benign and malignant tumors. The same variant was detected in the patient’s mother but not in the father or sibling. Given the association with schwannomatosis, screening for schwannomas was recommended, including annual clinical evaluations, baseline MRI, and follow-up MRIs every two to three years beginning at age twelve or earlier if symptoms appear. Further genetic testing, including RNA analysis of NF1 and analysis of TSC1/2, PTEN, and NF2, was also recommended. This case brings awareness to considering LZTR1 mutations in patients with multiple asymptomatic CALMs, particularly when more common causes such as NF1 and SPRED1 have been ruled out. Hannah Chang¹, Mariam Iqneibi², Kalyani Marathe² 1. University of Texas Southwestern Medical School, Dallas, TX, United States. 2. Dermatology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States. Genetic Disease, Gene Regulation, Gene Therapy & Epigenetics