Ichthyosis follicularis atrichia photophobia syndrome

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.

Ichthyosis follicularis - alopecia - photophobia (IFAP) is a rare genetic disorder characterized by the triad of ichthyosis follicularis, alopecia, and photophobia from birth.

Prevalence is unknown. Approximately 40 cases have been reported to date. IFAP primarily affects male subjects. Female carriers may develop some clinical features.

All patients present with congenital follicular ichthyosis, alopecia involving the scalp, eyebrows and eyelashes, and photophobia (in the first year of life, infancy or early childhood). Ichthyosis follicularis is characterized by widespread non-inflammatory thorn-like follicular projections. Hyperkeratotic papules are most pronounced over the extensor extremities and scalp and are distributed symmetrically. Non-cicatricial complete body alopecia is also a classical feature. Variable degrees of a collodion membrane may be present in newborns. Psoriasiform plaques, angular cheilitis, periungueal inflammation, dystrophic nails, hypohidrosis and atopic eczema can be present. The palms and soles are generally unaffected. Superficial corneal ulceration and vascularization may lead to progressive corneal scarring. Male patients have relentless progression of corneal vascularization and loss of vision. Atopic keratoconjunctival inflammation, chronic tearing, cataract, horizontal nystagmus, astigmatism and myopia have been reported. In a few cases, mild to severe intellectual disability, short stature, microcephaly, seizures, dysmorphic features (frontal bossing, choanal atresia, large ears), cleft hands, intestinal anomalies (omphalocele, Hirschsprung disease or congenital aganglionic megacolon (see these terms), small intestine stenosis, inguinal hernia), as well as renal, cardiac and vertebral anomalies can be present. Recurrent infections are common. External genitalia are generally normal with a few cases of cryptorchidism and one with hypospadias. Affected or carrier females may have milder symptoms (cutaneous hyperkeratotic lesions that follow the lines of Blaschko, asymmetric distribution of body hair, patchy alopecia).

The disorder is caused by mutations in the MBTPS2 gene (Xp22.12-p22.11) leading to impaired cholesterol homeostasis and response to endoplasmic reticulum stress.

Diagnosis is based on the clinical features and on testing of the MBTPS2 gene.

Differential diagnosis includes dermotrichic syndrome, hereditary mucoepithelial dysplasia, keratitis-ichthyosis-deafness (KID syndrome) and keratosis follicularis spinulosa decalvans (see these terms).

IFAP cannot be detected prenatally by ultrasound.

If the mutation has been identified in a carrier mother, prenatal diagnosis can be proposed. Transmission is X-linked recessive. The mutation might also arise de novo. A few cases of autosomal dominant inheritance have been reported.

Follicular hyperkeratosis can be treated using topical keratolytics, emollients and urea preparations. A moderate response to acitretin therapy has been found in some patients. Intensive lubrication of the ocular surface is essential. Corneal vascularization does not respond to topical corticosteroids.

Prognosis is variable. Some patients die in the neonatal period while others have normal life expectancy. However, in most patients, progressive loss of vision leads to loss of autonomy. Cardiopulmonary complications are the main cause of death.

Visit the Orphanet disease page for more resources.

Last updated: 8/1/2011

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