Clinical Guidance

A group of pathogenic variants (mainly located in exon 10) that result in impaired but not absent NF-kappaB signaling are associated with a milder IP phenotype in females and a lower risk of miscarriage of male fetuses. Additionally, most of these variants (which include missense, single base insertion/deletion causing frameshift, and nonsense variants) allow survival of males with hypohidrotic ectodermal dysplasia and immunodeficiency (HED-ID) and anhidrotic ectodermal dysplasia with immunodeficiency, osteopetrosis, and lymphedema (OLEDAID) .

Source: GeneReviews — "Incontinentia Pigmenti"

Penetrance

Incontinentia pigmenti has high penetrance. Most persons with IP appear to express the phenotype within a few months after birth. Expressivity, however, is highly variable. In addition, the skin findings can resolve over time and may be indistinguishable from other skin conditions with age. Furthermore, the dental, hair, and nail abnormalities can be managed cosmetically such that an affected adult woman may not have clinically evident diagnostic findings on physical examination.

Source: GeneReviews — "Incontinentia Pigmenti"

Diagnostic Criteria

Suggestive Findings

Incontinentia pigmenti (IP) should be suspected in individuals with characteristic clinical findings of the skin, teeth, hair, nails, eyes, and CNS, and family history as detailed below.

Major criteria (skin lesions that occur in stages from infancy to adulthood)

Source: GeneReviews — "Incontinentia Pigmenti"

Differential Diagnosis

A diagnosis other than incontinentia pigmenti (IP) should be considered when an individual has skeletal involvement (other than secondary to neurologic deficit), gross neurologic deficit, severe alopecia, atypical hyperpigmentation, or gross hypopigmentation. Body segment asymmetry is not usually associated with IP; however, one individual with IP and transverse terminal upper acromelia has been reported . The differential diagnosis for the skin manifestations of IP varies by stage. Because a child with IP may have an infectious comorbidity, findings consistent with an infectious disease should be evaluated accordingly, regardless of the presence of IP.

Source: GeneReviews — "Incontinentia Pigmenti"

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with incontinentia pigmenti (IP), the following evaluations are recommended if they have not already been completed:

• Physical examination with particular emphasis on the skin, hair, nails, and neurologic system to establish the presence and extent of manifestations

• Consultation with a clinical geneticist and/or genetic counselor

• Involvement of a pediatric dermatologist for management of individuals with significant skin involvement

• Prompt examination by an ophthalmologist familiar with IP and/or diseases of the retina for evidence of retinal neovascularization

• Brain MRI examination and referral to a neurologist for an EEG if seizures, other neurologic abnormalities, or retinal hypervascularization are present

• Magnetic resonance angiography, potentially useful in identifying cerebrovascular lesions if the neurologic deficit is consistent with a stroke-like pattern

• Developmental evaluation if significant delays are identified

• Involvement of a pediatric cardiologist for management of neonates with pulmonary hypertension

Treatment of Manifestations

Treatment includes the following:

Source: GeneReviews — "Incontinentia Pigmenti"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Incontinentia Pigmenti"

Surveillance Guidelines

No schedule for eye examinations has been established, but the following has been suggested:

• Monthly until age three to four months

• Every three months between ages four months and one year

• Every six months between ages one and three years

• Annually after age three years

Neurologic function should be assessed at routine visits with a pediatrician, pediatric neurologist, or developmental pediatrician. Ongoing evaluation by a pedodontist or dentist is appropriate.

Source: GeneReviews — "Incontinentia Pigmenti"