History

Usually, the diagnosis is made clinically on the basis of a history of sequential cutaneous lesions and associated features. Landy and Donnai have recommended the following diagnostic criteria.^{[8, 9]}

A least 1 major criteria is necessary for a diagnosis of sporadic incontinentia pigmenti. Major criteria include the following:

Typical neonatal rash
Typical hyperpigmentation
Linear, atrophic, hairless lesions.

Individuals with a least 1 first-degree female relative who was previously diagnosed with incontinentia pigmenti may also be diagnosed with minor criteria which include the following:

Dental involvement
Wooly hair, abnormal nails
Retinal disease

Physical

Four stages of skin change occur in most patients, mostly on the body along the sides of the torso. Few males develop stage 4 lesions.

Stage 1

Stage 1 is the vesicular stage, with linear vesicles, pustules, and bullae with erythema along the lines of Blaschko. This stage is present at birth but may recur during childhood with febrile illnesses. See the images below.

Incontinentia pigmenti. Linear streak of pigmentation and erythematous vesicles along the pattern of Blaschko lines on the left arm

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Forearm vesicles with overlying granulation tissue characteristic of incontinentia pigmenti

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Stage 2

Stage 2 is the verrucous stage, with warty, keratotic papules and plaques. Stage 2 occurs between ages 2 and 8 weeks.

Stage 3

Stage 3 is the hyperpigmented stage, with macular hyperpigmentation in a swirled pattern along the lines of Blaschko. These changes often involve the nipples, axilla, and groin. Stage 3 occurs between ages 12 and 40 weeks. See the images below.

Incontinentia pigmenti. The back and buttock region are covered with swirls and streaks of hyperpigmentation and purple discoloration with patches of vesicles, all along the lines of Blaschko.

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Incontinentia pigmenti. Streaks of hyperpigmentation on the chest and proximal right arm

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Stage 4

Stage 4 is the hypopigmented stage, with hypopigmented streaks and/or patches and cutaneous atrophy. Stage 4 is present from infancy through adulthood.

Recurrent papular skin eruptions have also been reported.

Onychodystrophy or nail dysplasia occurs in 40-60% of patients with incontinentia pigmenti. Other nail changes can include subungual keratotic tumors.

Ocular changes are seen in about one third of female patients and in two thirds of male patients with incontinentia pigmenti.^{[10, 11]}The changes can include the following:

Retinal pigmentary changes with mottled diffuse hypopigmentation, which is nearly pathognomonic
Abnormal peripheral retinal vessels with areas of nonperfusion, which is also nearly pathognomonic
Microphthalmia
Retrolental mass formation (pseudoglioma or retinoblastoma with intraocular calcifications)
Cataracts, leukocoria, or band keratopathy
Strabismus
Optic atrophy or foveal hypoplasia
Congenital glaucoma
Blue sclera
Exudative retinal detachment can be very rapidly progressive (< 6 mo) or fluctuate over many years.
Retinal pigmentary changes

Teeth and jaw changes occur in approximately 65-90% of patients. These changes can include delayed eruption of teeth; caries; partial anodontia; hypodontia; microdontia; abnormally shaped teeth—round, conical, or peg; micrognathia; prognathia; and gothic palate. Areas of focal hypermineralization and decreased enamel mineralization can also occur.

The hair is thin and sparse; alopecia is seen in 35-70% of people with incontinentia pigmenti. The hair changes can include a wooly hair nevus, which is a coarse, lusterless, and wiry patch of hair.

The central nervous system is involved in 10-40% of patients.^{[11, 12]}The manifestations can include the following:

Microcephaly
Mental retardation
Spasticity
Seizures (can present in the neonatal period)
Ataxia
Encephalopathy (can present in the neonatal period)
Hyperactivity
Strokes (can present in the neonatal period) (See the image below.)

Diffuse cerebral infarcts and edema associated with incontinentia pigmenti
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Encephalocele^[13]

Skeletal and structural anomalies can occur in approximately 14% of patients but are usually associated with severe neurological deficits. The anomalies can include the following:

Somatic asymmetry
Hemivertebrae
Scoliosis
Spina bifida
Syndactyly
Acheiria (congential absence of the hands)
Ear anomalies
Extra ribs
Skull deformities
Breast anomalies can occur in 1% of patients; anomalies can include hypoplasia and supernumerary.

Primary pulmonary hypertension

Cardiopulmonary failure

Causes

Most cases are caused by a deletion in the NEMO gene. Approximately one half of all cases are spontaneous mutations. Most of the new mutations occur in the germline cells in the father's gonads.

Female carriers may have only subtle findings with stage 4 skin and teeth abnormalities.
Males with XXY (ie, Klinefelter syndrome) have been reported. Other males who survived are believed to have postzygotic mutation, half chromatid mutation, an unstable permutation, somatic mosaicism, or hypomorphic mutations. Not all males have evidence of NEMO mutations and may have findings unilaterally or even just in one limb.
Almost all women with incontinentia pigmenti have skewed inactivation of the defective X chromosome, which may become more pronounced over time, as it is not always detected in newborns.

Differential Diagnoses

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Media Gallery

Incontinentia pigmenti. Linear streak of pigmentation and erythematous vesicles along the pattern of Blaschko lines on the left arm
Forearm vesicles with overlying granulation tissue characteristic of incontinentia pigmenti
Incontinentia pigmenti. The back and buttock region are covered with swirls and streaks of hyperpigmentation and purple discoloration with patches of vesicles, all along the lines of Blaschko.
Incontinentia pigmenti. Streaks of hyperpigmentation on the chest and proximal right arm
Diffuse cerebral infarcts and edema associated with incontinentia pigmenti