POLA1 XLPDR

This website provides information on patients with mutations in the POLA1 gene, including clinical data, molecular data, management and research options. This website was created to share and collect information about clinic, management and research projects to gather more knowledge and provide better treatment of patients with mutations in the POLA1gene.

XLPDR is caused by a specific mutation in the POLA1gene that causes tissue-specific partial missplicing of the POLA1 transcript. XLPDR is a multisystem autoinflammatory disorder characterized by reticulate skin hyper/hypopigmentation beginning in infancy, characteristic facial appearance (frontally upswept hair and flared eyebrows), recurrent pulmonary infections and bronchiectasis, hypohidrosis, and corneal scarring and photophobia. Lung disease can be severe, resulting in fatal pneumonia or chronic hypoxemia warranting evaluation for lung transplantation. Lung manifestations can resemble cystic fibrosis and due to low or absent sweat production precluding sweat chloride testing, XLPDR cases can be misdiagnosed in early life. Less frequent manifestations include intestinal inflammation, manifested as chronic diarrhea in the first year of life, and urethral strictures. Female carriers may be asymptomatic but usually exhibit patchy hyperpigmentation following lines of Blaschko as their only manifestation.

Other hypomorphic mutations in the POLA1gene cause Van Esch–O’Driscoll syndrome (VEODS), a multisystem disorder characterized by intellectual disability, short stature, microcephaly, hypogonadism, and variable congenital anomalies affecting multiple organ systems.

Affected individuals may also present with developmental delay, endocrine abnormalities, behavioral features, and structural malformations. At least one case of VEODS also displayed recurrent infections and immunological changes overlapping with XLPDR (NK cell lymphopenia).

Clinicians who identify a patient with a mutation in POLA1are invited to submit this information to the database.

Ezra Burstein, MD, PhD, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, United States, Ezra.Burstein@UTSouthwestern.edu
Andrew Zinn, MD, PhD, McDermott Center for Human Growth and Development, UT Southwestern Medical Center, Dallas, Texas, United States, Andrew.Zinn@utsouthwestern.edu