Virginia Research Day 2025

Medical Student Research Case Reports

24 Multiple Hereditary Exostoses with Café-Au-Lait Macules: A Rare Phenotypic Variation in a Pediatric Patient

Pranav Yanambakkam, OMS-III; Dr. Pamela Myers, MD, FAAP Corresponding author: pyanambakkam@vcom.edu Edward Via College of Osteopathic Medicine - Virginia Campus Highlands Pediatrics, Abingdon Virginia Multiple hereditary exostoses (MHE) is a rare autosomal dominant skeletal disorder characterized by multiple osteochondromas, primarily affecting the long bones. It is caused by mutations in the EXT1 or EXT2 genes and is typically not associated with cutaneous manifestations. Café-au-lait spots, common in neurofibromatosis type 1 (NF1), are rarely observed in MHE. Here, we present a unique case of a pediatric patient with MHE who also exhibits café-au-lait macules, highlighting the potential for an expanded phenotypic spectrum. This case involves a 6-year 11-month-old Hispanic male who was diagnosed with MHE on September 10, 2021, by a UVA Genetics team following identification of an EXT1 gene mutation. The patient presents with multiple exostoses, raising concerns for growth plate intrusion and potential risk for chondrosarcoma transformation due to his

pediatric age, which requires ongoing surveillance by pediatric orthopedics. Additionally, he has three café-au-lait spots, including a one-inch macule with “coast of Maine” borders on the right flank, as well as one-inch and 0.5-inch macules on the right upper lumbar and left upper thoracic regions, respectively. He has also been noted to have developmental delay and recently failed a vision screening, prompting an ophthalmology referral. His management is coordinated by genetics and orthopedics to address both skeletal and developmental needs. The presence of café-au-lait spots in a patient with MHE is unusual, as these cutaneous features are traditionally linked to NF1. While MHE and NF1 are separate genetic disorders, the overlap in clinical features observed in this case suggests the possibility of novel or under-recognized phenotypic variation

in MHE. Given the distinct genetic etiologies, this case raises questions about whether café-au-lait spots might occasionally manifest independently in patients with MHE or represent a coincidental finding. The patient’s developmental delay further emphasizes the need for comprehensive evaluation in atypical MHE presentations to rule out additional syndromic features. This case of MHE with café-au-lait macules presents an atypical clinical profile, underscoring the potential for expanded phenotypic features in MHE. Careful surveillance is essential, as these findings may have implications for diagnostic accuracy and patient management. Continued multidisciplinary care, including orthopedic and genetic follow-up, is critical for early detection of complications and optimizing the care pathway in pediatric MHE patients with unique clinical characteristics.

116