Dermatologic manifestations of Hermansky-Pudlak syndrome in patients with and without a 16-base pair duplication in the HPS1 gene

Background: Hermansky-Pudlak syndrome (HPS) consists of oculocutaneous albinism, a platelet storage pool deficiency, and lysosomal accumulation of ceroid lipofuscin. Patients with HPS from northwest Puerto Rico are homozygous for a 16-base pair (bp) duplication in exon 15 of HPS1, a gene on chromosome 10q23 known to cause the disorder. Objective: To determine the dermatologic findings of patients with PIPS. Design: Survey of inpatients with HPS by physical examination. Setting: National Institutes of Health Clinical Center, Bethesda, Md (a tertiary referral hospital). Patients: Sixty-five patients aged 3 to 54 years were diagnosed on the basis of the absence of platelet dense bodies in individuals with albinism and a bleeding diathesis. The presence of a 16-bp duplication in HPS1 was determined by polymerase chain reaction amplification; 40 patients were homozygous for the duplication and 25 lacked the duplication. All patients with the duplication were from northwest Puerto Rico; all patients without the duplication were non-Puerto Rican except 4 from central Puerto Rico. Results: Both patients homozygous for the 16-bp duplication and patients without the duplication displayed skin color ranging from white to light brown. Patients with the duplication, as well as those lacking the duplication, had hair color ranging from white to brown and eye color ranging from blue to brown. New findings in both groups of patients with HPS were melanocytic nevi with dysplastic features, acanthosis nigricans-like lesions in the axilla and neck, and trichomegaly. Eighty percent of patients with the duplication exhibited features of solar damage, including multiple freckles, stellate lentigines, actinic keratoses, and, occasionally, basal cell or squamous cell carcinomas. Only 8% of patients lacking the 16-bp duplication displayed these findings. As a group, the patients with the duplication lived closer to the equator than those without the duplication. Conclusion: Patients with PIPS exhibit wide variation in pigmentation and dermatologic findings.