SNP Shot: Genomic Insights

Incontinentia pigmenti (IP) is a multi-system disorder, with the skin being the most commonly affected area. This condition is significantly more prevalent in females than in males.

IP is characterized by distinctive skin changes that evolve throughout childhood and young adulthood. A common early manifestation is a blistering rash present at birth or shortly thereafter. While this blistering typically resolves on its own, it can reappear during periods of fever. Following the blistering stage, wart-like (verrucous) lesions may develop, which also spontaneously heal. These blisters and wart-like lesions are predominantly found on the arms and legs.

During infancy and early childhood, the skin often develops swirling patterns of grey or brown patches (hyperpigmentation). These patches can appear anywhere on the body and tend to fade over time. In adulthood, individuals with IP often exhibit lines of unusually light skin (hypopigmentation) on their arms and legs. These lighter markings correspond to the paths of cell migration during skin development before birth, known as the lines of Blaschko.

Individuals with IP face an increased risk of stroke and vision loss, particularly within the first year of life. These risks stem from abnormalities in blood vessels within the brain and within the retina (the light-sensitive tissue lining the back of the eye). Affected individuals at risk may experience developmental delays, intellectual disabilities, seizures, or other neurological complications. However, in the absence of stroke or other brain abnormalities, most individuals with IP have normal cognitive function.

Other potential signs and symptoms of IP include hair loss (alopecia) affecting the scalp and other body areas, dental abnormalities (such as small or missing teeth), and ridges or pits in the fingernails and toenails. The features of IP can vary in severity and may lessen or disappear entirely by adulthood.

Inheritance:

IP is inherited in an X-linked dominant manner. The gene responsible for this condition resides on the X chromosome, one of the two sex chromosomes. In females (who possess two X chromosomes), a mutation in just one copy of the gene in each cell is sufficient to cause the disorder. Some cells will produce a normal amount of IKBKG protein, while others will produce none. The resulting imbalance in cells producing IKBKG protein causes the signs and symptoms of IP. In males (who have only one X chromosome), most IKBKG mutations lead to a complete absence of the IKBKG protein. The lack of this protein is often fatal early in development, explaining the rarity of IP in males. Surviving males with IP may have a milder IKBKG mutation, a mutation present in only some of their cells (mosaicism), or an extra X chromosome in each cell. Some individuals with IP inherit the IKBKG mutation from an affected parent. Other cases arise from new (de novo) mutations in the gene, occurring in individuals with no family history of the disorder.