DISEASE CARD

Disease group Ectodermal Dysplasia
DISEASE NAME INCONTINENTIA PIGMENTI
Synonymous ~ 1:40000
Estimated prevalence -
OMIM 308300
Inheritance x-linked dominant
Gene (s) IKK-gamma (300248)

Definition

Incontinentia Pigmenti (IP) is a rare X-linked dominant genodermatosis characterized by a swirling pattern of skin hyperpigmentation. Affected females may also have variable abnormalities of the eyes, teeth, hair and central nervous system. Bloch and Sulzberger first described the entire clinical features of the condition in 1928, hence the synonymous name of Bloch-Sulzerger syndrome. The disease is caused by a mutation in the IKK-gamma (NEMO) gene, which maps to Xq28.

Clinical Description

The most prominent clinical feature in IP is the characteristic ‘4-stages’ of cutaneous rash. The majority of individuals present at, or soon birth, with an erythematous, inflammatory vesiculo-bullous eruption.

This rash is usually distributed on the scalp and extremities and may last for several weeks to months. During the second stage, which may last for up to 12 months, rough, verrucous papules develop with areas of increased pigmentation. The third ‘hyperpigmented’ stage usually presents when infants are between 6 and 12 months old and consists of the characteristic swirled pattern of hyperpigmentation on the trunk and limbs. However, these areas of discoloration tend to fade as the child becomes older. The final ‘atrophic’ stage consists of pale scarring and reduced pigmentation with a similar distribution to the previous eruptions.

These tend to fade with time and, in most cases, the cosmetic appearance improves remarkably as the affected individual reaches adulthood. The majority of individuals will experience some problems with dentition. Teeth may be fewer in number with an abnormal ‘peg-shaped’ appearance. About 50% will experience a degree of hair loss, usually in the form of scalp alopecia, thought to be due to areas of scarring. Hair that is present, may be abnormal in texture ie coarse, wiry and uncombable. Neurological abnormalities are extremely uncommon, and may include seizures, paralysis and mental retardation. Very rarely, eye defects may occur, the most severe being vascular abnormalities of the retina and disorders of the retinal pigment epithelium.

Pathogenesis

Familial IP is an X-linked dominant disorder caused by a mutation in the NEMO (NF-kappa B Essential MOdulator) gene. Nearly all NEMO mutations caused frameshift and premature protein truncation, which are predicted to eliminate NEMO function and cause cell lethality. It is thought that the evolution of the cutaneous eruptions is secondary to death of cells that have the mutant X chromosome, with replacement by cells with the normal X chromosome.

Diagnosis

Diagnosis is usually made by assessment of the clinical features either at, or soon after birth. Mutation analysis of the NEMO gene will supplement the clinical diagnosis and provide further supportive evidence to enable accurate genetic counselling. A skin biopsy that demonstrates melanin pigmentary incontinence will confirm the diagnosis.

Treatment

The various cutaneous manifestations seen in infancy generally resolve spontaneously. Areas of hyperpigmentation and atrophy will gradually improve and may disappear by the time the child reaches adolescence or adulthood. Dental treatment is important for these individuals as many may require successive dentures as a child with addition of dental implants and bridges later in adult life.

Refractive eye problems can usually be managed effectively with corrective lenses, however in some cases individuals may require surgical management. Females with IP should have regular ophthalmological examinations in the first years of life to enable early detection of retinal vascular abnormalities or retinal pigment epithelium disorders. Neurological defects will require assessment and management advice from a consultant neurologist.