X-linked reticulate pigmentary disorder (XLRPD), previously known as familial or X-linked cutaneous amyloidosis, is an exceedingly rare genetic disorder with distinct skin and systemic manifestations. Both X-linked recessive and dominant modes of inheritance have been suggested. Intronic mutation of POLA1, which encodes the catalytic subunit of DNA polymerase-α, is responsible for this condition. This mutation results in aberrant splicing and diminished expression of the gene, which ultimately leads to enhanced activity of type I interferon and reduced levels of interferon-γ and interleukin-17A. These changes are thought to account for the autoinflammatory and immunodeficient sequelae of XLRPD.

Affected males present during early childhood with diffuse reticulate (netlike) hyperpigmentation, interspersed with hypopigmented macules. These pigmentary changes are usually not present at birth, but rather initially develop as hypopigmented macules affecting the flexures. These asymptomatic spots may then spread to involve the face, trunk, and extremities, after which hyperpigmented macules arise within the hypopigmented areas. Extracutaneous manifestations in male patients include unique facial features of upswept frontal hairline and arched eyebrows, photophobia due to corneal opacification, hypohidrosis, recurrent respiratory infection with resultant pulmonary fibrosis, gastrointestinal inflammation, urethral strictures, nephrolithiasis, seizures, and developmental delay.

In contrast, female carriers of XLRPD exhibit only cutaneous involvement with the development of patchy hyperpigmentation along the lines of Blaschko during early childhood. There are no known systemic manifestations.