The exact pathogenesis of poliosis in most cases is unknown or only speculative. Possible causes are extensive, and this condition frequently occurs in the setting of several genetic syndromes.³ Although poliosis is not specific for any of these syndromes, it may be the initial presentation even before other more characteristic manifestations appear.⁴

Piebaldism is an autosomal dominant inherited disorder that most commonly develops secondary to a mutation in the c-kit proto-oncogene on chromosome 14q12 that affects melanoblast migration, proliferation, differentiation, and survival.⁵,⁶ It is characterized clinically by the presence of congenital poliosis and leukoderma,⁷ with a white forelock and poliosis of the eyebrows and eyelashes seen in 80% to 90% of cases.¹

Tuberous sclerosis is an autosomal dominant disorder characterized by hamartoma development in various tissues, most frequently the brain, skin, heart, kidneys, and lungs.⁸ It is caused by mutations in the TSC1 (9q34) or TSC2 (16p13) genes resulting in activation of the mechanistic target of rapamycin (mTOR) signaling pathway. More than half of cases present with seizures, and dermatologic manifestations may be seen initially in more than 90% of affected children.⁴,⁹ Hypopigmented skin macules are identified in infancy or early childhood in 15% to 50% of patients.⁴,⁹ Although poliosis is not one of the diagnostic criteria, it is often present as one of the earliest signs of the disease and may precede the appearance of other manifestations.⁴

Waardenburg syndrome type I is a rare autosomal dominant disorder of neural crest cell development associated with a heterozygous pathogenic variant in PAX3 (2q36). It is characterized by sensorineural deafness and pigmentary abnormalities, often associated with a white forelock and possible poliosis of eyebrows and eyelashes.³,¹⁰ Other ophthalmic manifestations may include segmental heterochromia, or hypoplastic or brilliant blue irides, and segmental choroidal hypopigmentation.¹¹ Depigmentation in Waardenburg syndrome is caused by the absence of melanocytes from the affected areas in the skin, hair, eyes, or ears.¹⁰,¹²

Poliosis has also been reported rarely in patients with Rubinstein-Taybi syndrome,¹³,¹⁴ Marfan syndrome,¹⁵ and neurofibromatosis type 1.¹⁶

Vogt-Koyanagi-Harada (VKH) syndrome is a rare, nongenetic, systemic T cell-mediated autoimmune inflammatory disorder. It is characterized by bilateral uveitis that is frequently associated with neurological, auditory, and integumentary manifestations. The etiology and pathogenesis are not completely understood, but it is believed that
the clinical manifestations are caused by an autoimmune response directed against melanin-associated antigens in the target organs, such as the eye, inner ear, meninges, and skin. Accumulating evidence suggests that predisposing genetic factors, including VKH disease-specific risk factors (HLA-DR4), general risk factors for immune dysfunction (increased Expression of IL-23 Receptor [IL-23R]), environmental triggers (eg, viruses), and recently COVID-19 vaccinations, are all involved in the development of VKH disease.¹⁷,¹⁸ The clinical manifestations of VKH include vitiligo occurring in association with poliosis, uveitis, aseptic meningitis, tinnitus, dysacusis, and alopecia.¹⁷,¹⁸,¹⁹,²⁰,²¹,²² Vitiligo, poliosis, and alopecia usually develop in the late phase of the disease, although they can manifest earlier. Periocular hair involvement is common in this disorder and usually manifests as eyelash poliosis.

Alezzandrini syndrome is a very rare disease with only a few cases reported in the literature.²³,²⁴ The etiology is unknown but several theories involving viral or autoimmune processes have been postulated. The disease is characterized by hearing abnormalities, unilateral tapetoretinal degeneration, ipsilateral facial vitiligo, and poliosis. It is suspected that an autoimmune process destroys melanocytes.²³,²⁴

Vitiligo is a chronic pigmentary disorder characterized by loss of epidermal melanocytes leading to depigmented skin macules.²⁵ The exact cause of the loss of functional melanocytes in affected skin is not fully understood, but it is believed that a triggering event leads to a stress response in the skin that initiates an autoimmune response against melanocytes in genetically predisposed individuals.²⁶ Genetic predisposition is supported by the fact that 25% of patients with vitiligo have a positive family history and more than 40 gene variants have been identified in genome-wide association studies.²⁷ The melanocyte destruction has been attributed to several mechanisms such as autoimmune, cytotoxic, neural, and viral causes.²⁵ Poliosis, especially of the eyebrows, can be associated with vitiligo in up to 48% of cases, especially in patients with segmental vitiligo.²,²⁸,²⁹