Immunodeficiency in a female patient with Incontinentia Pigmenti

Abstract

Incontinentia pigmenti (IP) is a rare X-linked dominant neuroectodermal disorder characterized by ocular, dermatologic, and neurological abnormalities. It is caused by heterozygous mutations in IKBKG (NEMO), which encodes a regulatory factor involved in NF-kB activation. Random and skewed X-inactivation allows for female survival and determines extent of disease. Although immune function is typically normal in IP patients, hypomorphic IKBKG mutations are known to cause immunodeficiency, as occurs in X-linked NEMO deficiency. A female newborn presented with bullous vesicles, peeling skin, alopecia, hearing loss, and tonic-clonic seizures with MRI demonstrating evidence of in utero stroke. She developed intermittent fevers and cellulitis and was diagnosed with IP based on clinical findings. Following discharge, she was readmitted at 1 month of age due to bronchiolitis complicated by pulmonary abscess. Labs demonstrated hyperleukocytosis with hypereosinophilia, normal T, B, and NK lymphocyte enumeration, abnormal lymphocyte proliferation to phytohemagglutinin (PHA) and anti-CD3, and abnormal toll-like receptor (TLR) function. Genetic analysis revealed a heterozygous deletion of exons 4–10 in IKBKG. Labs at 1 year follow up showed normal lymphocyte (T, B, and NK) enumeration and mitogen responses, normal immunoglobulin levels, and normal responses to pneumococcal and tetanus vaccines. While about 70% of IP patients harbor a deletion of exons 4–10 in IKBKG. unlike other hypomorphic NEMO mutations, this mutation is not typically associated with altered immune function. This case highlights that immunodeficiency may be an early clinical manifestation in female patients with IP.