Ichthyosis Follicularis, Alopecia, and Photophobia (IFAP) Syndrome Due to Mutation of the Gene MBTPS2 in a Large Australian Kindred

Abstract

Ichthyosis follicularis, alopecia and photophobia (IFAP) is a rare genodermatosis. Most patients have been men without significant family history. We present the largest kindred of IFAP reported to date in the medical literature clearly demonstrating X-linked inheritance. The gene defect has recently been mapped to Xp22.11-p22.13. Missense mutations of the gene, MBTPS2, which codes for an intramembrane zinc metalloprotease essential for cholesterol homeostasis and endoplasmic reticulum stress response, are associated with the IFAP phenotype in this kindred. We describe the clinical features and discuss the differential diagnosis of IFAP. Our proband has benefited from treatment with acitretin.

Expanding the phenotype of IFAP/BRESECK syndrome: A new case with severe hypogammaglobulinemia

“…There are several reports of patients with recurrent skin and respiratory infections but normal immunoglobulin levels [8,12,15]. There is a report of one patient with recurrent upper respiratory infections and pneumonia with immunological screening showing IgG 2 levels slightly under average [11].…”

Cholesterol homeostasis: Links to hair follicle biology and hair disorders

“…Glycerol kinase 5 (GK5) inhibits SREBP processing; however, the mechanism through which this occurs is unknown . Mutations to MBTPS2 are associated with IFAP and KFSD in which alopecia is present . C, Representation of putative cholesterol transport and trafficking routes in hair follicle keratinocytes.…”

Ichthyosis follicularis, alopecia, and photophobia (IFAP) syndrome

“…A moderate response to acitretin therapy at a dose of 0.3 to 1 mg/Kg/day with improvement in cutaneous features and corneal erosions but no changes regarding alopecia and photophobia have been noted in some patients [11,15]. Otherwise, follicular hyperkeratosis can be treated using topical keratolytics, urea preparations, and emollients.…”