Updated Review of Genetic Reticulate Pigmentary Disorders

J. Zhang; M. Li; Z. Yao


The British Journal of Dermatology. 2017;177(4):945-959. 

In This Article

X-linked Reticulate Pigmentary Disorder

XLRPD (once called X-linked cutaneous amyloidosis) was first reported in 1981.[61] Affected males develop generalized hyperpigmentation intermingled with small hypomelanotic macules during early childhood, forming a reticulate pattern. Moreover, male patients show a distinctive face characterized by an upswept frontal hairline and arched eyebrows, along with other systemic complications such as severe photophobia, recurrent respiratory infections, and severe gastrointestinal disorders. In female carriers, the type and distribution of the pigmentation mimics that of incontinentia pigmenti (IP; patchy pigmentary skin lesions along the lines of Blaschko), without any systemic manifestations.[62] In affected adults, a deposition of amyloid-like material in the papillary dermis can be observed on histopathology. In 2008, genetic linkage studies mapped the causal gene to a 4·9-Mb interval, Xp22·11–p21·3.[63] Very recently, an intronic mutation c.1375–354A>G in POLA1 was found to be responsible for this disorder – a primary immunodeficiency with autoinflammatory and reticulate pigmentary features.[64] The POLA1 gene encodes the catalytic subunit of DNA polymerase-α, which acts as a critical regulator of the type I interferon response.[64] Future studies can focus on the role of DNA polymerase-α in immune regulation, pigmentogenesis and as a potential therapeutic target.

Differential Diagnosis

The differential diagnosis of XLRPD includes DUH, and the two are sometimes clinically indistinguishable; some male patients with characteristic faces and recurrent respiratory tract infections have thus been misdiagnosed with DUH.[65] Molecular testing and review of family history facilitates effective differentiation. The other similar disease is amyloidosis cutis dyschromica, which presents similar features such as dotted, reticular hyperpigmentation with hypopigmented macules distributed over nearly all of the body (Figure 8), as well as focal amyloid deposition in the papillary dermis. The disease is distinguished by the lack of characteristic facial features and other complications, different onset age (before puberty vs. infancy) and by the pattern of inheritance.

Figure 8.

Clinical features of amyloidosis cutis dyschromica: dotted, reticular hyperpigmentation with hypopigmented macules are distributed over nearly all of the patient's body; occasionally lichenoid papules can be found.

Clinical Management

Treatment is tailored to the complications of the affected individual. Prenatal genetic advice is needed for affected adult patients.