DFNA1 is an autosomal dominant form of progressive hearing loss with onset in the first decade. Some patients have mild thrombocytopenia and enlarged platelets, although most of these individuals do not have significant bleeding tendencies (summary by Neuhaus et al., 2017).

Hermansky-Pudlak syndrome (HPS) is characterized by oculocutaneous albinism, a bleeding diathesis, and, in some individuals, pulmonary fibrosis, granulomatous colitis, and/or immunodeficiency. Ocular findings include nystagmus, reduced iris pigment, reduced retinal pigment, foveal hypoplasia with significant reduction in visual acuity (usually in the range of 20/50 to 20/400), and strabismus in many individuals. Hair color ranges from white to brown; skin color ranges from white to olive and is usually at least a shade lighter than that of other family members. The bleeding diathesis can result in variable degrees of bruising, epistaxis, gingival bleeding, postpartum hemorrhage, colonic bleeding, and prolonged bleeding with menses or after tooth extraction, circumcision, and/or other surgeries. Pulmonary fibrosis, colitis, and/or neutropenia have been reported in individuals with pathogenic variants in some HPS-related genes. Pulmonary fibrosis, a restrictive lung disease, typically causes symptoms in the early 30s and can progress to death within a decade. Granulomatous colitis is severe in about 15% of affected individuals. Neutropenia and/or immune defects occur primarily in individuals with pathogenic variants in AP3B1 and AP3D1.

Thrombocytopenia-7 (THC7) is an autosomal dominant disorder characterized by reduced peripheral platelet count. The expression and severity of the disorder is highly variable: some patients have no bleeding symptoms, whereas other have recurrent petechiae, epistaxis, or more severe bleeding episodes. A common finding is decreased alpha-granules in the platelets. There are variable findings on light and electron microscopic analysis: some patients have normal platelet morphology, whereas others show abnormal platelet morphology with cytoskeletal defects. Flow cytometric studies may show reduced expression of platelet membrane glycoproteins and activation markers (summary by Lentaigne et al., 2019 and Leinoe et al., 2021). For a general phenotypic description and a discussion of genetic heterogeneity of thrombocytopenia, see 313900.

Platelet-type bleeding disorder-25 (BDPLT25) is an autosomal dominant condition characterized by increased susceptibility to bleeding episodes due to decreased or dysfunctional platelets. Some individuals have decreased numbers of enlarged platelets or macrothrombocytopenia, whereas others have normal numbers of enlarged platelets. Platelet morphologic and functional defects are variable (Pleines et al., 2017; Stapley et al., 2022; Marin-Quilez et al., 2022). For a discussion of genetic heterogeneity of BDPLT, see 231200.