Hermansky-Pudlak syndrome

Hermansky-Pudlak syndrome is a multi-system disorder that primarily affects pigmentation, bleeding, and organ function. It is associated with variants in several genes, including DTNBP1, AP3B1, BLOC1S5, BLOC1S3, BLOC1S6, and AP3D1, which play important roles in the formation and function of lysosome-related organelles. The condition is classified as rare and affects approximately 1 to 9 individuals per million. Although manifestations can appear early in life, the range and severity of symptoms vary considerably between affected individuals.

Individuals with Hermansky-Pudlak syndrome most commonly present with ocular findings such as nystagmus, iris hypopigmentation, and other visual disturbances including photophobia and reduced visual acuity. In addition, the skin and hair exhibit hypopigmentation and many experience bleeding issues such as abnormal bleeding tendencies, bruising susceptibility, and epistaxis. Some affected individuals may also develop decreased neutrophil counts, immunodeficiency, renal insufficiency, or pulmonary fibrosis as the condition progresses. Not all individuals experience every feature, and severity varies considerably.

Hermansky-Pudlak syndrome is linked to variants in several genes including DTNBP1, AP3B1, BLOC1S5, BLOC1S3, BLOC1S6, and AP3D1. These genes are involved in the production and function of organelles related to pigmentation and blood clotting, and disruptions in their normal activity lead to the characteristic features of the syndrome. Although specific details regarding the inheritance pattern are not provided in this packet, genetic alterations in these genes are recognized as the underlying cause, and families may benefit from genetic counseling to understand any potential implications. Associated genes include DTNBP1, AP3B1, BLOC1S5, BLOC1S3, BLOC1S6.