H SYNDROME: An Exceptional Case of Non-Langerhans Histiocytosis with Clinical and Genetic Insights

Abstract

H syndrome is a rare autosomal recessive genodermatosis characterized by a unique form of non-Langerhans histiocytosis caused by mutations in the SLC29A3 gene, which encodes the nucleoside transporter hENT3. This condition leads to impaired nucleoside transport, resulting in exaggerated inflammatory responses and abnormal histiocytic proliferation. We report a 28-year-old Moroccan man presenting with hyperpigmentation and hypertrichosis of the lower limbs for over 20 years, accompanied by hearing loss, cardiac anomalies, and spinal deformities. Genetic analysis revealed compound heterozygosity for pathogenic variants in the SLC29A3 gene, confirming the diagnosis of H syndrome. H syndrome typically manifests with cutaneous symptoms such as hyperpigmentation and hypertrichosis, as well as systemic issues including hearing loss, cardiac anomalies, short stature, and diabetes. The wide phenotypic variability complicates diagnosis and management. Recognizing the genetic basis of H syndrome is essential for accurate diagnosis and appropriate management. While systemic corticosteroids have shown some effectiveness, no consensus on optimal treatment exists due to the condition's complexity and rarity. Early identification and genetic counseling are critical for affected families. H syndrome is an exceptionally rare condition with diverse clinical manifestations, highlighting the need for awareness and accurate diagnosis to prevent unnecessary interventions.