A Brazilian case of IFAP syndrome with severe congenital ichthyosis and limb malformations caused by a rare variant in MBTPS2

Um caso brasileiro de síndrome IFAP com ictiose congênita grave e malformações de membros causadas por uma variante rara em MBTPS2

Abstract

Objective:

The classic triad, which defines IFAP syndrome, is ichthyosis follicularis, alopecia, and photophobia. It is a rare X-linked genetic disorder characterized by multiple congenital anomalies with variable severity, caused by pathogenic variants in the MBTPS2 gene, which encodes a zinc metalloprotease that is essential for normal development. This study aimed to report a case of a Brazilian patient with IFAP syndrome presenting skeletal anomalies, which is a rare finding among patients from different families.

Case description:

We describe a male proband with IFAP syndrome showing severe ichthyosis congenita, cryptorchidism, limb malformation, and comprising the BRESHECK syndrome features. Using whole-exome sequencing, we identified a rare missense variant in hemizygosity in the MBTPS2 gene, which had not been identified in other family members.

Comments:

This is the first diagnosis of IFAP syndrome in Brazil with a molecular investigation. The present case study thus expands our knowledge on the mutational spectrum of MBPTS2 associated with IFAP syndrome.

Keywords:
MBTPS2; Ichthyosis congenital; Limb malformations; BRESHECK syndrome; IFAP syndrome