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At a glance

It is a genetic disease characterized by unusual patterns of discolored skin. During the first stage, skin redness and spiral lines of blisters are encountered. Second stage includes warty skin on the arms and legs. Third stage is associated with discolorations of the skin but also hair (kinky hairs) and teeth. Other features include central nervous system dysfunction (spina bifida, skull deformity), dwarfism, clubfeet, cleft palate/lip, syndactyly, retinal vascular abnormalities, blindness, and congenital dislocation of the hips.

Synonyms

Bloch-Sulzberger Syndrome; Bloch-Siemens Syndrome with Incontinentia Pigmenti; Familial Incontinentia Pigmenti; Melanoblastosis Cutis Linearis; Pigmented Dermatosis, Siemens-Bloch Type.

History

Genodermatosis was first described by A. E. Garrod (1906), but the condition was defined by M. Bardach, Bruno Bloch, Swiss dermatologists, Hermann Werner Siemens, a German dermatologist, and Marion Baldur Sulzberger, an American dermatologist, during the 1920s.

Incidence

The international incidence in the general population has been estimated at 1:40,000. Up until the late 1980s, only 700 cases had been reported; however, the disease probably is not as rare as once thought because single simple cases are not usually described in the literature. Incontinentia pigmenti is a genodermatosis that can be associated with malignancies (ie, Chromosomal Instability Syndrome), such as acute myelogenous leukemia, Wilms tumor, malignant rhabdoid tumors, and retinoblastoma. It is more common in Caucasians than in other races. Women with incontinentia pigmenti have a 2:1 female-to-male offspring ratio. The overall male to female ratio is 1:37. The initial skin lesions are present at birth.

Genetic inheritance

X-linked dominance with lethality in males. Gene map locus is Xq28. It affects almost only females (90-95% of cases) (Lyon effect). (Sporadic incontinentia pigmenti, usually termed hypomelanosis of Ito or incontinentia pigmenti Type I, is a distinct disorder but has many features similar to those of incontinentia pigmenti; it is mapped at chromosome Xp11.21.)

Pathophysiology

Caused by a defective gene in the X chromosome, the NEMO gene (nuclear factor-κB essential modulator gene). It is an essential cellular protein allowing cells to respond to outside signals, such as growth factors. The evolution of lesions is the consequence of the death of cells bearing the mutant X chromosome and their replacement by cells with the normal X active chromosome.

Diagnosis

The cutaneous manifestations are diagnostic and present at birth. The name incontinentia pigmenti describes the characteristic histologic feature of incontinence of melanin from the melanocytes in the basal layer of the epidermis into the superficial dermis. Histologically, deposits of melanin pigment are seen in the corium: the designation was based on the idea that the basal layer of the epidermis is “incontinent” of melanin. The gene responsible for the disorder (NEMO gene) has been identified, thus allowing molecular testing and diagnosis.

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