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, club feet, cleft palate/lip, syndactyly, retinal
vascular abnormalities, blindness, and congenital dislocation of the hips.
First stage of incontinentia pigmenti with spiral lines and blisters on
the skin of the legs in a 5-month-old infant.
Hyperpigmentation and linear vesiculation on the feet of an infant with
Bloch-Sulzberger Syndrome; Bloch-Siemens Syndrome with
Incontinentia Pigmenti; Familial Incontinentia Pigmenti; Melanoblastosis
Cutis Linearis; Pigmented Dermatosis, Siemens-Bloch Type.
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.
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 (i.e., 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
initial skin lesions are present at birth.
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.)
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.
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 ...